Environmental Monitoring Critical Areas

Environmental Monitoring Critical Areas, Environmental monitoring within a pharmaceutical company is crucial to ensure the quality and safety of products. Key focal point for Environmental Monitoring Critical Areas in this context include:

  • Air Quality
  • Water Systems
  • Temperature and Humidity Control
  • Environmental Microbiology
  • Personnel Monitoring
  • Utility Systems
  • Waste Management
  • Environmental Control during Transportation
  • Regulatory Compliance
Cleanrooms and Controlled Environments:

Cleanrooms and controlled environments are regularly monitored to ensure they meet clean air standards. Maintain the required level of cleanliness by monitoring particulate and microbial contamination.

Continuous monitoring of cleanrooms and controlled environments is essential to ensure compliance with stringent air purity standards. This continuous monitoring is an important aspect of quality control and carefully evaluates both particulate and microbial contamination to ensure that these environments consistently meet the required cleanliness levels.

In real-world situations, industries such as pharmaceuticals demonstrate the importance of such careful monitoring. In pharmaceutical manufacturing facilities, cleanrooms play an important role in ensuring that pharmaceutical production is free from contaminants that can affect quality and effectiveness. By regularly monitoring and auditing air purity, pharmaceutical companies can protect the integrity of their products, ensure compliance with regulatory standards, and ultimately ensure the safety of consumers who rely on their medicines.

 

Additionally, industries such as semiconductor manufacturing also rely heavily on cleanroom technology. In this context, careful monitoring of air quality is essential to prevent the introduction of the smallest particles that can affect the precision and performance of sensitive electronic components. Deviations from the required cleanliness standards in these environments can lead to defects in semiconductor devices and potentially malfunctions in electronic devices and systems.

 

In essence, continuous monitoring of cleanrooms and controlled environments goes beyond theoretical compliance. Ensuring product quality, regulatory compliance, and ultimately user well-being is a practical necessity across a variety of industries.

 

Air Quality:

Air quality in production areas is the another Environmental Monitoring Critical Areas, is continuously monitored to control particulate matter, microbial contamination, and volatile organic compounds (VOCs). Ventilation systems are tested regularly to verify efficiency and proper filtration.

Continuous monitoring of air quality in production environments plays an important role in managing various air pollutants such as fine dust, micropollutants, and volatile organic compounds (VOCs). This continuous monitoring not only ensures compliance with regulatory standards, but also protects the health and well-being of both workers and the surrounding community.

For example, imagine a pharmaceutical manufacturing plant where strict quality control is essential. It is important to continuously monitor air quality to prevent the release of particulate and microbial contaminants that can impact the production of sterile pharmaceutical products. Advanced air quality monitoring systems allow facilities to immediately detect deviations from acceptable levels, allowing rapid corrective action to be taken to maintain a controlled and sterile manufacturing environment.

Monitoring also goes beyond simple detection and includes regular testing of ventilation systems. This includes evaluating the efficiency and adequacy of air filtration processes, which are critical to maintaining a clean and contamination-free workplace. Practical applications for this include semiconductor manufacturing plants, where microchip production requires extremely clean environments. Regularly testing your ventilation system will ensure that your air filter elements are operating optimally and prevent the introduction of particles that can affect the accuracy and performance of sensitive electronic components.

In essence, continuous monitoring of air quality in production areas through regular testing of ventilation systems is an example of a proactive approach to environmental protection and regulatory compliance. This not only improves the overall quality of our manufacturing processes, but also highlights our commitment to creating a safe and sustainable work environment.

 

Water Systems:

Monitors the quality of water used in pharmaceutical processes, including purified water and water for injection. Regular testing for microbial contamination, endotoxins and chemical contamination.
Ensuring the quality of water used in pharmaceutical operations, whether for purified or injectable purposes, is critical to maintaining product integrity and patient safety. Compliance monitoring includes rigorous testing to detect microbial contamination, endotoxins, and chemical contaminants to ensure the reliability of pharmaceutical products.

In fact, this rigorous quality control process involves the use of advanced analytical techniques and sophisticated equipment to assess the purity of the water. For example, microbiological testing may involve using special culture media to cultivate and identify potential microbial contaminants. This ensures that the water meets rigorous standards set by regulatory bodies such as pharmacopoeia or health authorities.

To illustrate this concept further, consider a pharmaceutical manufacturing facility that produces injectable drugs. The water used to make these medications must be carefully tested. Regular testing for endotoxins, potentially harmful substances secreted by some bacteria, is essential. An example of a real-world scenario is the detection of endotoxin levels in water samples using the Limulus amoebocyte lysate (LAL) test, a common method in the pharmaceutical industry. This test helps ensure the safety and effectiveness of the final drug product by ensuring that the water used in the manufacturing process is free of endotoxins.

Chemical contaminants in the water, such as heavy metals and organic compounds, are also carefully tested. This may include using advanced analytical tools such as high-performance liquid chromatography (HPLC) or mass spectrometry to identify and quantify contaminants present. By performing these comprehensive analyses, pharmaceutical companies maintain the highest standards of water quality, contributing to the overall safety and effectiveness of their products.

In summary, careful monitoring of water quality in pharmaceutical processing through comprehensive testing for microbial contamination, endotoxins, and chemical contaminants is important to ensure the safety and efficacy of pharmaceutical products. Specific examples, such as the use of the LAL test to detect endotoxins and advanced analytical techniques to evaluate chemical contaminants, highlight the pharmaceutical industry’s commitment to maintaining rigorous quality standards in the use of water.

 

Temperature and Humidity Control:

Monitor and control temperature and humidity in storage areas to ensure the stability of pharmaceutical products. Validation of temperature-controlled storage and transport systems.
Monitoring and controlling temperature and humidity in storage facilities plays a critical role in maintaining the integrity and effectiveness of pharmaceutical products. The purpose of this rigorous oversight is to ensure the safety of these sensitive medicines and ensure that they meet the rigorous standards required for their intended use. A key aspect of this process is validating temperature-controlled storage and transportation systems to meet the pharmaceutical industry’s commitment to quality and safety.

A real-world scenario shows a pharmaceutical warehouse equipped with sophisticated sensors and control systems to carefully monitor temperature and humidity. These facilities use advanced technology to continuously monitor environmental conditions and immediately detect and correct deviations from prescribed parameters. For example, pharmaceutical companies can use integrated monitoring systems that communicate directly with storage devices and adjust temperature controls in real time to maintain optimal conditions required for product stability.

The verification process extends beyond static storage areas to the transport phase, recognizing the critical role it plays in maintaining the integrity of pharmaceutical products. Imagine a scenario where vaccines are transported across continents using temperature-controlled shipping containers. These containers undergo a rigorous verification process to ensure they can maintain specified temperature ranges throughout their travel. The container’s advanced monitoring devices enable real-time adjustments during transport with sophisticated control systems and protect medicines from possible environmental fluctuations.

In essence, careful monitoring and verification efforts for temperature and humidity control not only highlight the pharmaceutical industry’s commitment to product quality, but also how technological advances are used to maintain the integrity of pharmaceutical products from storage to transportation and ultimately ensure their effectiveness. It shows that it works. And safety. This is for end users.

 

Environmental Microbiology:

Regularly monitor surfaces, equipment and personnel for microbial contamination. Identify and control potential sources of contamination in your production environment.
Continuous surveillance of surfaces, equipment, and personnel is essential to effectively detect and address microbial contamination. Continuous monitoring of these components is critical to maintaining the integrity of the production environment. By carefully monitoring and eliminating potential sources of contamination, companies can ensure the production of high-quality, pollution-free products.

In a real-life scenario, imagine a pharmaceutical company maintaining strict protocols in its manufacturing plant. Surfaces, production facilities and employees are regularly inspected for signs of microbial contamination. This careful monitoring includes regular swab testing of machines, sampling to disinfect surfaces, and health checks of workers working in production areas.

For example, if routine inspections reveal germs on critical equipment, immediate action is taken to isolate the contaminated area, conduct a thorough investigation, and take corrective action. This proactive approach helps prevent the spread of contamination that impacts the quality of manufactured medicines.

Moreover, identifying and controlling potential sources of contamination goes beyond the physical aspects of the manufacturing process. This includes assessing and improving employee hygiene practices, ensuring appropriate hygiene clothing is worn, and implementing strict hygiene measures. In this way, the company reduces the risk of contaminants entering the production process and ensures a clean and controlled environment.

In summary, careful and systematic monitoring of surfaces, equipment and personnel combined with identifying and controlling potential sources of contamination is not only a theoretical best practice, but also a practical and important aspect of ensuring the quality and safety of products in medicinal industry.

 

Personnel Monitoring:

Monitor and audit employee hygiene practices, including dressing procedures and hand hygiene. Regularly test employees working in areas where microbial contamination is significant.

Monitoring and reviewing employee hygiene practices is an essential part of maintaining germ-free conditions and includes careful dressing procedures and strict hand hygiene. Additionally, regular testing is essential to identify and minimize the risk of microbial contamination for people working in critical areas.

In a real-world scenario, imagine a pharmaceutical manufacturing facility where maintaining strict hygiene protocols is critical. Cleanroom personnel must follow specific dressing procedures and wear sterile clothing to prevent the introduction of contaminants. Hand hygiene, including proper hand washing and use of disinfectants, is becoming an important factor in reducing the risk of bacterial infection.

Regular testing for microbial contamination includes regular assessments of employees working in critical areas such as cleanrooms and laboratories. This may include cleaning surfaces, monitoring air quality, and monitoring workers for microorganisms. For example, in the pharmaceutical industry, workers are regularly tested for microbiology to ensure compliance with hygiene standards and to identify potential sources of contamination.

By continuously implementing and monitoring these hygiene practices, companies can maintain rigorous quality standards that ensure the integrity of their processes and the safety of their products. This method is suitable not only for the pharmaceutical industry, but also for a variety of other industries where maintaining a sterile or controlled environment is important, including biotechnology, food manufacturing, and electronic manufacturing.

 

Utility Systems:

Monitor critical supply systems such as compressed air, gases, and steam to prevent microbial and particulate contamination. Check the performance and cleanliness of your utility systems.

Continuous monitoring of critical supply systems is essential to detect and mitigate potential microbial and particulate contamination, including but not limited to compressed air, gases, and vapors. This continuous monitoring protects the integrity of a variety of industrial processes by verifying the functionality and cleanliness of utility systems.

In fact, imagine a pharmaceutical manufacturing facility where compressed air plays a critical role in maintaining a sterile environment. Regular monitoring of your compressed air system can detect microbial contaminants or particulates that can affect pharmaceutical quality. By verifying the efficiency and cleanliness of the delivery system, facilities ensure compliance with regulatory standards and ensure safe and effective drug production for end users.

Continuous monitoring of steam quality is also essential in the food and beverage industry, where steam is used in a variety of processes. Detecting and removing microbial contaminants or particulates in vapors ensures food integrity and maintains rigorous quality and safety standards. This proactive approach not only helps maintain your brand’s reputation, but also increases consumer confidence in product safety.

Fundamentally, careful monitoring and validation of ICU systems goes beyond compliance requirements. This is essential to maintain the reliability, efficiency and safety of industrial processes across a variety of sectors, thereby preserving product quality and ensuring the well-being of end users.

 

Waste Management:

Properly dispose and monitor pharmaceutical waste to prevent environmental contamination. Comply with regulations regarding disposal of hazardous materials.
Proper disposal and careful monitoring of pharmaceutical waste is essential to protect the environment from potential contamination. This includes adhering to strict regulations on the disposal of hazardous substances to minimize the impact of pharmaceutical waste on the environment.

In real-world situations, pharmaceutical waste includes expired drugs, unused drugs, and other materials generated during manufacturing and distribution. Improper disposal of these materials can contaminate soil, water and air, posing a serious threat to human and environmental health.

To illustrate, imagine a pharmaceutical manufacturing plant that produces a variety of drugs. Waste generated during manufacturing, including chemicals and unused by-products, can remain in the environment if not properly managed and disposed of. This pollution can impact local water resources, harm aquatic life, and potentially enter the food chain.

To prevent such situations, it is essential to comply with the regulations regarding mediation. Neutralizing or segregating hazardous pharmaceutical waste requires the introduction of safe and environmentally friendly disposal methods, such as incineration or safe landfilling. Regular monitoring will help ensure consistent compliance with these disposal practices and detect and correct any deviations that may cause harm to the environment.

In summary, careful management and monitoring of pharmaceutical waste is essential to minimize environmental impact. By strictly adhering to regulations and implementing responsible waste management practices, we can protect ecosystems and public health from the harmful effects of improper disposal of pharmaceuticals.

 

Environmental Control during Transportation:

Environmental conditions are monitored and verified during pharmaceutical transport to prevent decomposition.

It is important to ensure the integrity of pharmaceutical products during transport to prevent quality degradation due to fluctuations in environmental conditions. Monitoring and validating these conditions plays a critical role in maintaining the effectiveness and safety of medicines from the point of manufacture to the end user.

For example, imagine a scenario where a pharmaceutical company ships a temperature-sensitive vaccine to a remote location. Without proper monitoring and verification procedures, vaccines may be exposed to extreme temperatures during transport, compromising their quality and effectiveness. Using rigorous monitoring systems, including temperature sensors and data loggers, companies can actively monitor and record temperature fluctuations during operation. This real-time data allows immediate action to be taken in case of deviations from recommended storage conditions.

Additionally, our verification process ensures that the selected shipping method complies with industry standards and regulatory requirements. This involves ensuring that the packaging materials and separation methods effectively protect the drug from external influences, and in our example validation would involve testing the delivery of the vaccine under various simulated conditions to ensure that the selected packaging complies with the required temperature range. can.

By focusing on monitoring and validating environmental conditions, pharmaceutical companies can ensure product quality, comply with regulatory guidelines, and ultimately contribute to the overall effectiveness of medical interventions. This commitment to quality assurance is critical in the pharmaceutical industry, where minor deviations in environmental conditions can have serious impacts on the health and well-being of end users.

Regulatory Compliance:

Ensure compliance with relevant regulatory standards and guidelines, such as: to meet Good Manufacturing Practices (GMP) quality and safety requirements.

Effective environmental monitoring programs in these focus areas contribute to overall pharmaceutical quality assurance and regulatory compliance, mitigate risks associated with contamination, and ensure the safety and effectiveness of manufactured pharmaceutical products.

To maintain quality and safety standards in the pharmaceutical industry, compliance with relevant regulatory standards and guidelines, especially Good Manufacturing Practices (GMP), is essential.

For example, careful adherence to GMPs ensures that pharmaceutical companies adhere to strict procedures throughout the manufacturing process, including aspects of facility cleanliness, equipment maintenance, and employee training. This helps companies maintain consistent, high-quality pharmaceutical production to meet regulatory expectations.

Additionally, implementing an effective environmental monitoring program in key operational areas will significantly improve quality assurance and compliance in pharmaceutical manufacturing. Imagine a scenario where a pharmaceutical facility uses advanced monitoring systems to assess air and water quality, temperature, and humidity. These real-time monitoring efforts reduce potential contamination risks by quickly detecting and correcting deviations from established standards.

In essence, a robust environmental monitoring program acts as a proactive measure to address potential contaminants before they threaten the integrity of the pharmaceutical product. This not only meets legal requirements, but also protects end users by ensuring that the medicines produced are always safe and effective.

Environmental Monitoring Procedure as per Pharmacopeia

In summary, combining a comprehensive environmental monitoring program with strict compliance with regulatory standards such as GMP is critical to ensuring the quality and safety of pharmaceutical products. These measures not only reduce the risks associated with contamination, but also contribute significantly to maintaining the effectiveness of medicines and are consistent with the pharmaceutical industry’s overall goals of regulatory compliance and consumer protection.

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Environmental Monitoring Procedure as per Pharmacopeia

Environmental Monitoring Procedure in accordance to Pharmacopeia, The British Pharmacopoeia (BP) provides guidelines for environmental monitoring procedures to ensure the quality and safety of pharmaceutical products. Here’s an overview of environmental monitoring procedures as per the BP:

  • Scope
  • Microbial Monitoring
  • Particulate Monitoring
  • Sampling Methods
  • Analysis and Testing
  • Acceptance Criteria
  • Documentation and Record Keeping
  • Quality Control and Assurance

 

Scope

BP outlines environmental monitoring requirements for pharmaceutical manufacturing facilities, including clean rooms, sterile manufacturing areas, and other critical areas where product quality can be affected by environmental conditions.

The business plan (BP) outlines the stringent requirements for monitoring environmental parameters in a pharmaceutical manufacturing facility. This guidance covers several important areas such as clean rooms, sterile manufacturing areas, and other critical areas where environmental conditions affect product quality.

Specifically, let’s assume that a pharmaceutical company starts producing a new vaccine. Within manufacturing facilities, it is important to comply with environmental monitoring requirements. For example, clean rooms must maintain a certain level of air purity to prevent contamination of sensitive biological materials. Aseptic manufacturing areas require precise temperature and humidity control to ensure product integrity. Failure to comply with these environmental standards can impact vaccine effectiveness and safety, potentially leading to regulatory upheaval or even public health concerns.

We also consider the implications of environmental monitoring from the perspective of real-world events. Imagine a scenario where environmental conditions in a pharmaceutical facility deviate from prescribed values due to equipment malfunction. Without timely detection and intervention, hazardous substances can enter the manufacturing process, jeopardizing the quality and safety of the pharmaceutical products produced. This can lead to costly product recalls, damage a company’s reputation, and more importantly, pose health risks to patients.

Therefore, careful implementation of the environmental monitoring protocols outlined in your business plan will not only ensure compliance but also protect against potential risks to both product quality and public health.

 

Microbial Monitoring: 

BP emphasizes the importance of microbial monitoring to detect and control microbial contamination in production environments. This includes regular air, surface and personnel sampling to determine microbial levels and identify potential sources of contamination.

The importance of microbial monitoring highlighted by BP cannot be overemphasized, especially in ensuring product quality and safety in manufacturing environments. Microbial contamination poses a significant threat to industries ranging from medicine to food production. By implementing rigorous microbial monitoring protocols, companies can effectively identify and contain potential sources of contamination, protecting both consumer health and brand reputation.

For example, imagine a pharmaceutical manufacturing plant that produces life-saving drugs. Microbial contamination during manufacturing may affect the effectiveness and safety of this medication and put patients at risk. Regular sampling of air, surfaces and personnel allows companies to proactively monitor microbial levels and quickly detect any deviations from acceptable standards. By identifying the source of contamination, such as inadequate sterilization procedures or improper handling practices, immediate corrective action can be taken to prevent further spread and preserve product quality.

Additionally, microbial monitoring in the food industry plays an important role in preventing food poisoning. Imagine a food processing plant that produces prepared foods. Failure to monitor microbial contamination can lead to widespread outbreaks and costly recalls due to the presence of harmful bacteria such as salmonella or listeria. Regular sampling of your production environment and workforce can help you identify and proactively address potential sources of contamination, such as cross-contamination of raw materials or poor hygiene practices, to protect consumers.

In essence, microbial monitoring is not just a regulatory requirement but a fundamental aspect of manufacturing quality assurance. By prioritizing these aspects of manufacturing, companies can maintain the highest standards of safety and integrity, ultimately increasing trust among both consumers and stakeholders.

 

Particulate Monitoring: 

Particle monitoring is also important for maintaining cleanliness in production areas. BP provides guidance on sampling methods and acceptable limits for particulate contamination in various cleanroom classifications.

It is essential to ensure cleanliness of the production site through careful monitoring of fine dust. This careful monitoring is important not only to maintain optimal production conditions, but also to ensure product quality and workplace safety.

Imagine a pharmaceutical manufacturing plant producing sensitive drugs. Here, even the smallest particles can affect the performance and safety of the final product. Therefore, implementing rigorous particulate monitoring protocols is essential.

The British Pharmacopoeia (BP) provides valuable guidance on this topic by describing sampling methods and setting acceptable thresholds for particulate contamination in various cleanroom classifications. These standards serve as a benchmark for industries around the world and provide a framework for assessing and maintaining the level of cleanliness required to meet regulatory requirements and quality standards.

For example, meeting BP’s stringent particulate limits in a cleanroom dedicated to the production of sterile injectable drugs helps ensure that the final product is free of contaminants that could pose a risk to patient health. Regularly monitoring and following these guidelines not only ensures compliance but also increases consumer confidence in the integrity of manufactured products.

Additionally, the importance of monitoring goes beyond compliance. Emphasizes excellence in the manufacturing environment and a commitment to continuous improvement. By regularly assessing and mitigating particulate contamination risks, companies can optimize production processes, reduce waste, and increase operational efficiency.

In essence, active particulate monitoring in production areas, regulated by standards such as BP, serves as the basis for quality assurance and emphasizes our commitment to excellence in product manufacturing.

 

Sampling Methods: 

BP specifies sampling methods for environmental monitoring, including active air sampling, sediment sampling, and surface swabbing. Sampling location and frequency are determined by risk assessment and production area classification. Best Practices (BPs) describe comprehensive techniques for conducting environmental monitoring and include a variety of sampling methods such as active air sampling, sediment sampling, and surface swabbing. These methods serve as important tools for assessing and mitigating potential environmental risks in industrial environments. To illustrate, let us consider a pharmaceutical manufacturing facility that follows these protocols.

These situations may require the use of special equipment to capture airborne particles and contaminants at specific locations within an active air sampling facility. Sediment plate sampling may require strategically placing sterile plates in various areas to collect sedimented particles over time. Surface cleaning involves systematically cleaning surfaces to detect contamination or microbial residues.

The choice of sampling location and frequency is not arbitrary and is based on rigorous risk assessment. For example, areas where sensitive materials must be handled during the manufacturing process or where there is a high risk of contamination may require more frequent monitoring. Conversely, spaces with lower risk profiles may require less frequent sampling.

Additionally, the classification of production areas plays an important role in determining the intensity and focus of monitoring efforts. For example, clean rooms typically require rigorous monitoring because they play a critical role in maintaining product quality and safety. In contrast, administrative areas may require minimal monitoring due to their lower risk exposure.

By following these guidelines, pharmacy facilities can proactively identify potential environmental hazards, implement targeted interventions, and maintain rigorous quality standards. This highlights the importance of strong environmental monitoring practices in industrial environments, not only ensuring regulatory compliance but also protecting public health and environmental integrity.

 

Analysis and Testing: 

Samples collected as part of environmental monitoring are analyzed using BP’s specific microbiology and analytical techniques. Microbial counting methods, such as agar plate counting and membrane filtration, are often used to measure microbial contamination levels. During environmental monitoring, samples are analyzed using microbiological and analytical methods described in Best Practice (BP) guidelines. These technologies play an important role in assessing the quality and safety of a variety of environments, from water bodies to industrial sites. For example, when monitoring microbial contamination at a wastewater treatment plant, samples are collected at various stages of the treatment process.

The collected samples undergo extensive analysis using techniques such as agar plate counting and membrane filtration. In agar plate counting, samples are spread on an agar medium in a Petri dish, microbial colonies are grown, and then counted to determine the concentration of microorganisms present. This method provides information about the overall microbial load of the sample.

During membrane filtration, the sample passes through a filter with a defined pore size that captures microorganisms. These microorganisms are then transferred to growth media where they form visible colonies that can be counted and analyzed. This technique is particularly useful for quantifying specific types of microorganisms or pathogens present in a sample.

These microbiological enumeration methods allow environmental scientists and regulators to accurately measure levels of microbial contamination in a variety of environmental samples. This information is important for making informed decisions about managing and protecting environmental resources, ensuring public health, and meeting regulatory requirements.

 

Acceptance Criteria: 

BP sets acceptance criteria for microbial and particulate contamination based on manufacturing area classification and product requirements. This standard sets maximum allowable contamination limits to ensure product quality and safety. The biopharmaceutical (BP) industry sets stringent acceptance criteria to protect against microbial and particulate contamination, which vary depending on the classification of production area and specific product requirements. These criteria play an important role in ensuring the quality and safety of the final product by determining the upper contamination threshold that is considered acceptable.

To illustrate, imagine a pharmaceutical company that produces sterile injectable drugs. Within a facility, various areas are classified based on cleanliness and potential risk of contamination. For example, critical areas such as clean rooms where pharmaceuticals are manufactured will have more stringent acceptance criteria than areas such as hallways or administrative offices.

The type of product manufactured also affects acceptance criteria. Products designed to be injected directly into the bloodstream, such as insulin, require extremely low limits for microbial and particulate contamination to prevent potential risk to patients. In contrast, topical creams may have slightly higher tolerance limits because they do not enter the bloodstream directly.

These acceptance criteria are not arbitrary. This is carefully determined through rigorous scientific analysis and takes into account factors such as product durability, shelf life and potential health risks. For example, if a cleanroom is assigned ISO Class 5, this means that only a limited number of particles of a certain size are allowed per cubic meter of air. This ensures that the environment is strictly controlled to prevent contamination of the products produced.

In essence, compliance with these acceptance criteria is essential to maintain product integrity and ensure patient safety. Failure to meet these standards can result in product recalls and regulatory fines, and most importantly, it can put consumers’ health at risk. Therefore, pharmaceutical companies invest significant resources into monitoring and maintaining compliance with these standards throughout the manufacturing process.

 

Documentation and Record Keeping: 

Pharmaceutical companies are required to keep detailed records of their environmental monitoring activities in accordance with BP guidelines. This includes documentation of sampling procedures, test results, corrective actions, and deviations from established standards. BP guidelines require pharmaceutical companies to maintain accurate records of their environmental monitoring efforts. These records include complete documentation of various aspects, including sampling procedures, test results, corrective actions taken, and deviations from predetermined standards. To further explore this requirement, let’s look at a real-world example.

Consider XYZ Pharmaceuticals, a pharmaceutical company that operates a manufacturing plant that produces a variety of drugs. As part of our commitment to environmental sustainability and compliance, XYZ Pharmaceuticals strictly adheres to the BP Directive, which requires rigorous environmental monitoring practices.

Within the facility, some staff members perform routine environmental sampling, collecting air, water, and soil samples from specific areas inside and outside the facility. These samples undergo rigorous testing to assess various parameters such as contamination levels, microbial contamination and overall environmental quality.

The documentation process begins with recording detailed information about the sampling method used, including the exact sampling location, sampling technique used, and equipment calibration details. Each sample is carefully labeled and recorded to ensure traceability and accountability throughout the process.

After analyzing the samples, test results are carefully documented and parameters such as contaminant concentration, presence of contaminants and compliance with legal limits are recorded in detail. When deviations from established standards are detected, appropriate corrective action is initiated.

For example, during routine monitoring of air quality, XYZ Pharmaceuticals detected a slight increase in particulate matter levels in its manufacturing area. They immediately find the root cause, which is a fault in the filter system. Corrective action will include immediate repair of the filtration system and additional sampling to determine the effectiveness of the corrective action taken.

It is best to keep complete records during this process. These documents are not only a historical record of environmental monitoring activities, but also an important testimony of the company’s commitment to environmental protection and regulatory compliance. In the event of a regulatory audit or investigation, these records provide transparency and assurance that the organization is carefully monitoring and managing its environmental impacts in accordance with established guidelines.

 

Quality Control and Assurance: 

Environmental monitoring procedures are an integral part of the quality control and assurance system implemented by pharmaceutical companies. Regular audits and inspections are carried out to ensure compliance with BP requirements and regulatory standards. Environmental monitoring procedures are an integral part of the quality control and assurance system implemented by pharmaceutical companies. Regular audits and inspections are carried out to ensure compliance with BP requirements and regulatory standards.

Environmental monitoring systems play an important role in the quality control and assurance systems established by pharmaceutical companies. These procedures include comprehensive measures to assess and control environmental factors that can potentially affect the quality and safety of the medicinal product.

To illustrate, consider a hypothetical pharmaceutical company called XYZ Pharmaceuticals that specializes in producing sterile injectable drugs. Throughout the manufacturing process, XYZ implements rigorous environmental monitoring protocols in line with guidance from regulatory authorities such as the British Pharmacopoeia (BP).

Environmental Monitoring Sop

As part of these procedures, XYZ periodically conducts audits and inspections of its manufacturing facilities to ensure compliance with BP requirements and regulatory standards. This includes parameters such as air quality, surface cleanliness, temperature, humidity and microbial contamination in critical areas such as cleanrooms and production areas.

For example, XYZ’s environmental monitoring program involves using specialized equipment such as air samplers, particle counters, and surface swabs to systematically assess the cleanliness and sterility of the manufacturing environment. By carefully following the protocols outlined in BP, XYZ can effectively reduce contamination risks and maintain product integrity.

Additionally, these monitoring methods are not limited to the production phase. XYZ Pharmaceuticals extends its environmental monitoring efforts to storage facilities, transportation processes, and distribution channels to ensure product quality throughout its life cycle. In essence, adhering to environmental monitoring procedures outlined in regulatory standards such as BP can help pharmaceutical companies like there is.

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Granulation Method Advancements

Granulation Method, During granulation, a critical step in pharmaceutical manufacturing, particles are enlarged using agglomeration techniques. This process is very important in the production of pharmaceutical dosage forms, especially tablets and capsules. By converting fine powders into free-flowing, dust-free granules, granulation allows them to be more easily compressed. However, this presents numerous challenges, mainly due to the stringent quality requirements for cast granules, covering aspects such as content uniformity and physicochemical properties such as granule size, bulk density, porosity, hardness, moisture content and shrinkage. Moreover, the physical and chemical stability of the drug makes the granulation process more complex.

There are two main types of granulation processes: wet granulation, which uses liquid, and dry granulation, which occurs without the use of liquid. Choosing an appropriate process requires, among other things, in-depth knowledge of the drug’s physicochemical properties, excipients, and desired flow and release characteristics.

Several technologies play an important role in granulation, including spray drying, roller compaction, high shear mixing, and fluid bed granulation. These techniques have proven effective in overcoming the challenges posed by fragmented processes. However, the field of pharmaceutical granulation technology is dynamic and constantly evolving with the introduction of new and innovative technologies.

This review highlights recent advances in granulation techniques and techniques and covers pneumatic dry granulation, Reverse wet granulation, steam granulation, moisture activated dry granulation, heat bond granulation, freeze granulation and expanded bond foam granulation. Provides insight. Each development is discussed with a brief description that highlights its importance and limitations and provides a comprehensive overview of the current pharmaceutical granulation technology landscape. For example, the advent of steam granulation represents an innovative way to obtain granulated structures by harnessing the power of steam, offering potential advantages in terms of efficiency and product quality. However, issues related to process control and scalability may limit widespread adoption in pharmaceutical manufacturing.

Granulation, a key technology in pharmaceutical manufacturing, involves particle growth through agglomeration and is considered one of the most important steps in the production of pharmaceutical dosage forms, especially tablets and capsules. This process converts small, fine or coarse particles into larger aggregates called granules. The initiation of granulation typically occurs after initial dry mixing of the powder ingredients and active pharmaceutical ingredient (API) to ensure uniform distribution throughout the powder mixture.

In the pharmaceutical industry, granules with a particle size of 0.2 to 4.0 mm are typically used as intermediate products in the 0.2 to 0.5 mm size range. These granules are packaged directly into dosage forms or mixed with other excipients before compressing tablets or filling into capsules. Granule production serves several purposes: B. Improved API uniformity, increased mixture density to improve storage and transportation efficiency, facilitate dosing or dose distribution, and reduce dust during granulation to reduce exposure to toxic substances and risks associated with the process and final product. The overall picture.

Ideal granule characteristics include a spherical shape for improved flowability, a narrow particle size distribution for uniform content and volume dosing, sufficient fineness to fill voids between granules for good compaction and compaction properties, and a fine particle size to prevent breakage and dusting. These include moisture content and sufficient hardness. Receive training in manufacturing.

Granulation is an example of particle design, and the properties of the particles after granulation include particle size of drug and excipients, type, concentration and volume of binder and/or solvent, granulation time and type of granulator, and drying rate (temperature and time). ). Composite particles are formed through processes such as solid bridging, sintering, chemical reaction, crystallization, colloidal particle deposition, adhesion, and cohesion using a high-viscosity binder. Processes involved in particle formation include wetting and nucleation, coalescence or growth, agglomeration, and attrition or cracking.

In tablet compression, a powder mixture containing pharmaceutical excipients and API can be compressed into tablets either directly or using agglomeration or granulation techniques after granulation. Granulation technology can be broadly divided into two types: dry granulation and wet granulation. Dry granulation involves mechanical compaction (screw) or compaction (roller compaction) to bring the dry powder particles together, while wet granulation uses a granulating fluid (binder/solvent) to form a wet mass through the members. Promotes coagulation. Despite the complexity, time and cost associated with multiple process units such as wet massage, drying and sieving, wet granulation remains the most widely used technique in pharmaceutical granulation, requiring a lot of space and multiple equipment.

Process selection for pharmaceutical granulation requires in-depth knowledge of the drug’s physicochemical properties, excipients, and desired flow and release characteristics. Over the years, granulation technologies such as roller compaction, spray drying, supercritical fluids, low/high shear mixing, fluidized bed granulation, extrusion/spheronization, etc. have proven successful in the production of various pharmaceutical dosage forms.

For example, consider roller compaction, a proven technology that compacts dusty materials between two counter-rotating rollers. This process is often used to produce granular pellets because it efficiently produces uniform particle sizes and improves flow characteristics. In real-world scenarios, pharmaceutical companies can use roller compression to improve the structure of tablets to ensure consistent drug release and optimal therapeutic effect.

The pharmaceutical granulation environment is dynamic and subject to continuous development and innovation. Over time, many improvements, modifications, and new techniques and technologies have emerged, reflecting the industry’s efforts to improve the pharmaceutical manufacturing process. These advances contribute to the development of more effective and patient-friendly medicines.

The purpose of this review is to provide readers with information about the latest technologies and techniques related to pharmaceutical granulation. By exploring ongoing developments in granulation technology, the pharmaceutical industry can keep abreast of advancements that can impact the efficiency, quality, and overall success of the drug manufacturing process.

 

Recent advances in wet granulation

Wet granulation is the most important and most used technology in pharmaceutical production. In this method, a granulating liquid, which may or may not contain a binder, is used to wet mix excipients and an active pharmaceutical ingredient (API) to form granules. Over time, wet granulation has undergone numerous developments, both from a technical and technical perspective, demonstrating its adaptability and versatility in pharmaceutical processes.

An important innovation in wet granulation is the introduction of steam granulation. This technology uses steam as the granulation medium, providing a controlled and efficient granulation medium. Applying steam improves the cohesion of the granules, improving the uniformity and quality of the final product. This innovation solves problems related to moisture content and distribution and contributes to the overall efficiency of the granulation process.

Another important advancement, moisture-activated dry granulation, involves using moisture to accelerate granulation without adding liquid binders. This technology offers the advantage of reducing processing time and energy consumption, making it a more sustainable and cost-effective option. Pharmaceutical manufacturers can leverage these innovations to streamline manufacturing processes and increase overall efficiency.

Heat adhesive granulation is a further development of wet granulation technology. This method produces granulation by promoting adhesion between particles through controlled heating. Precise application of heat ensures optimal binding and cohesion, resulting in granules with the desired properties. These innovations are examples of industry efforts to improve and optimize manufacturing processes for pharmaceutical formulations.

Melt granulation, a state-of-the-art method, uses a molten binder to bind particles into granules. This technology offers advantages in terms of better homogeneity and dissolution properties of the final product. Pharmaceutical formulations developed using melt granulation exhibit improved stability and bioavailability, demonstrating the potential of this approach to revolutionize drug delivery systems.

Freeze granulation is another innovative technology that produces granules by freezing. In this method, ice bridges are formed between particles, resulting in the development of well-defined and uniform particles. The freeze granulation process is particularly convenient for sensitive or heat labile substances and ensures the therapeutic integrity of the active ingredients.

Expanded binder or foam granulation represents a unique innovation in wet granulation in which a blowing agent is introduced to form a foam and then acts as a binder in the granulation process. This technology offers benefits such as improved flow properties and compressibility of the granules and contributes to the overall efficiency of downstream processing and tablet production.

Counter-wet granulation is an advanced variant in which dry powder is added to the wet mass to form granules. This method provides a controlled and efficient way to achieve granulation while minimizing the use of liquid binders. The Reverse wet granulation process provides better control of particle size distribution and better control of powder flow characteristics.

The continuous development of innovative wet granulation technologies such as steam granulation, moisture-activated dry granulation, heat adhesive granulation, melt granulation, freeze granulation, expanded binder or foam granulation and Reverse wet granulation is driving the pharmaceutical industry. is promising. We proceed with the production process. These innovations not only address the challenges of traditional wet granulation, but also provide solutions that improve the efficiency, product quality, and stability of pharmaceutical manufacturing.

 

  • Freeze granulation
  • Foam granulation
  • Melt granulation
  • Moisture-Activated Dry Granulation (MADG)
  • Reverse wet granulation
  • Steam Granulation
  • Thermal Adhesion Granulation (TAG)
Freeze Granulation

Freeze-drying technology, following cutting-edge spray freezing and freeze-drying methods, is revolutionizing granule production through the seamless integration of liquid nitrogen and advanced drying technology. This innovative process begins by carefully spraying small droplets of a slurry or suspension into liquid nitrogen to quickly condense them into granules. In the subsequent freeze-drying step, in which the frozen droplets are sublimated, spherical and free-flowing particles are formed without separation effects.

To understand the importance of this technology, let us consider its application in the pharmaceutical industry. Protects organic compounds from damage in mild environments through low temperature and freeze-drying, improving stability and solubility. The versatility of freeze-drying extends to a wide range of materials in disperse form, making it suitable for mixing fine powders with appropriate additives. What makes this process special is its unique ability to preserve the structure and homogeneity of the particles in the original slurry or suspension, which provides a major advantage for granulation where precise particle size and homogeneity are required.

Real-world applications demonstrate the wide-ranging benefits of this technology. Redispersible parenteral formulations, nanomaterials, and solid self-emulsifying drug delivery systems benefit greatly from granulation via freezing as they maintain size and homogeneity, which are critical for performance. Companies such as Powderpro AB, a spin-off of the Swedish Ceramic Institute, have been developing, producing and selling freeze granulation equipment using this technology since 2000.

This process is characterized by the following important advantages: B. Because there is no particle movement or molecular bonding, the concentration of particles can be controlled through suspended solids, void-free particles are produced, and high homogeneity is possible. The gentle drying process makes heat-sensitive compounds easier to use and broadens their application range. Additionally, the environmentally friendly use of water as a process medium contributes to sustainability, although it may suffer from the low solubility of some drugs and processing aids.

Freeze granulation technology has proven to be an innovative approach with far-reaching implications, shaping the granule manufacturing landscape across various sectors, especially the pharmaceutical industry. The ability to maintain particle size, homogeneity and structural integrity is an important tool in the arsenal of modern materials processing technologies.

Cold granulation, also known as cold granulation or cold casting, is a unique granulation technology that involves freezing a liquid suspension and then sublimating the freezing solvent to form a porous granule structure. Like any other process, cold granulation has advantages and disadvantages.

Advantages of Freeze Granulation

  • Porous Structure
  • Preservation of particle shape
  • Low shear
  • Particle size distribution control
  • Environmentally friendly
Porous Structure:

One of the main advantages is creating a very porous structure. The freeze-drying process forms a network of interconnected pores within the granules, which can improve properties such as dissolution rate and surface area in pharmaceutical and materials science applications.

 

Preservation of particle shape:

During freeze granulation, the original particle shape of the granulated material is often maintained. This can be important in applications where maintaining raw material properties is critical to product performance.

 

Low shear:

This process requires minimal shear force on the particles during granulation, which is beneficial in maintaining fine material properties that can be damaged by traditional granulation methods.

 

Particle size distribution control:

Granulation via freezing allows for more effective control of particle size distribution, resulting in more uniform granules. This is particularly advantageous for industries where particle size plays an important role in the properties of the final product.

 

Environmentally friendly:

This process generally uses water as a solvent, and the solvent can be recovered and reused, making freeze granulation relatively environmentally friendly compared to other granulation technologies that may use organic solvents.

 

Disadvantages of Freeze Granulation

  • Longer processing time
  • Equipment Complexity
  • Scalability Challenge
  • Energy intensive
Longer processing time:

Freeze granulation processes often require longer processing times than traditional granulation methods. Freezing and sublimation steps can increase overall production time and affect efficiency and productivity.

 

Equipment Complexity:

The equipment required for freeze granulation can be more complex and expensive. Special freezers and control systems are required to ensure a successful granulation process.

 

Scalability Challenge:

Scaling cryogranulation from laboratory scale to industrial scale can be difficult. As volumes increase, it becomes more difficult to achieve consistent results and maintain control over process variables.

 

Energy intensive:

This process can be energy intensive, especially during the freezing and sublimation steps. These aspects must be considered both in terms of operating costs and environmental impact.

 

Foam granulation

Foam granulation, an innovative technology similar to spray agglomeration, has revolutionized the process of incorporating liquid or water-based binders into powder particles. Unlike the traditional method of spraying or pouring a liquid binder onto the powder, foam granulation uses a foam binder. This innovative method was introduced by the Dow Chemical Company in 2003 and involves using a foam generator in a binder solution tank with a high shear or fluidized bed granulator. By introducing the binder into the foam rather than spraying or casting, this technology eliminates problems associated with inconsistent binder distribution that can affect tablet hardness and drug release in high shear and fluid bed wet granulation applications.

The unique advantage lies in the superior surface and volume properties of foamed binders compared to sprayed water. This technology uses these properties to improve binder distribution in the powder particles using lower amounts of binder than traditional spray granulation methods. Traditional spray methods often pose problems such as uneven wetting, excessive wetting, requiring excessive amounts of water and binder, and complex drying processes to remove excess water. In comparison, the expandable binder has high wettability, so the particles are well coated and do not overmoisten. The result is less binder, greater distribution, improved reproducibility and shorter processing times. Eliminating spray nozzles also reduces process fluctuations and clogging problems.

In addition to these advantages, foam granulation has proven to be useful for high potency/low dose drug formulations as it ensures uniform distribution of the drug. Additionally, minimal water consumption and short processing times make it suitable for water-sensitive formulations as well as immediate controlled release formulations. Standard equipment such as high/low shear mixers and fluid bed granulators combined with foam generators facilitate the smooth introduction of this technology.

Despite the numerous advantages, further research is needed to understand aspects such as foam quality, process parameters, device dynamics, flow patterns, and mixing behavior. Overcoming regulatory approval challenges is a significant hurdle and highlights the need for continued research and development in this innovative sector.

Advantages of foam granulation:

  • Improved delivery
  • Improved diffusion/absorption rate
  • Reduce processing time
  • Reduce the amount of binder
  • Spray nozzle troubleshooting
Improved delivery:

Compared to traditional spray granulation methods, foam granulation distributes the binder more uniformly and predictably into the powder particles.
Example: In pharmaceutical manufacturing, uniform tablet hardness and uniform binder distribution are critical to drug release.

 

Improved diffusion/absorption rate:

Foam binders have a high dispersion-wetting ratio, which is better for particle coating rather than overwetting. This contributes to increased efficiency and a more controlled process.
Example: In pesticide production, precise coating of granules is essential for efficient and targeted application.

 

Reduce processing time:

Foam granulation typically reduces overall processing time compared to traditional methods, increasing production efficiency.
Example: Rapid processing can be advantageous in industries such as food production, where it can increase overall productivity by reducing the time required for granulation.

 

Reduce the amount of binder:

This technology ensures effective granulation while using small amounts of binder. This helps you save money and reduce your environmental impact.
Example: The use of low-grade binders may be particularly advantageous for pharmaceutical products where reduced amounts of excipients are required.

 

Spray nozzle troubleshooting:

Eliminates problems associated with foam granulation spray nozzles such as clogging and processing variability, providing a more reliable and efficient manufacturing process.
Example: Avoiding nozzle problems is important when producing detergents where consistent granule size is critical to product performance.

Disadvantages of foam granules:

  • Device compatibility
  • Limited application
  • Regulatory barriers
  • Research and development requirements
Device compatibility:

Foam granulation adjustments may require modifications to existing equipment or additional components (e.g., foam generators), which may increase initial implementation costs.
Example: In the agricultural sector, adapting existing granulation systems to foam technology may require investment in new machinery.

 

Limited application:

Foam granulation may not be suitable for all materials or formulations, limiting its application to certain industries or processes.
Example: When producing certain specialty chemicals, traditional granular methods may still be preferred due to specific material properties.

Foam granulation offers many advantages in terms of improved binder distribution, reduced binder volume, and increased efficiency, but also presents challenges such as regulatory barriers, ongoing research requirements, equipment compatibility issues, and limited applicability of certain materials or processes.

 

Regulatory barriers:

This technology may have difficulty gaining regulatory approval and may require extensive documentation and validation to ensure compliance with industry standards.
Example: In the pharmaceutical industry, all new manufacturing methods must undergo rigorous regulatory review to ensure the safety and effectiveness of the product.

 

Research and development requirements:

More research is needed to fully understand foam quality, process parameters, and device dynamics. This can cause problems during the initial implementation phase.
Example: In the chemical industry, where new processes are constantly being developed, further research is essential to optimize and validate new production technologies.

 

Melt Granulation

Melt granulation, also called thermoplastic granulation, is a cutting-edge technology that uses soluble binders to promote fusion of powder particles. These binders have the unique property of melting or softening at relatively low temperatures (usually 50-90°C). The granulation process is a process in which the mixture of drug, binder, and other excipients is heated to dissolve or soften the binder, and then the solidified powder is cooled to solidify the molten binder to complete the granulation process.

For practical applications, consider the pharmaceutical industry, where fusion granulation has proven to be an invaluable tool. For example, in a melting process, a mixture of drug, binder, and other ingredients is heated to a temperature above the melting point of the binder. This process allows the incorporation of low melting point binders into solid particle form, making in situ melt granulation possible. However, the spray-on process involves spraying a molten binder, which may contain active ingredients, onto the heated powder, offering a variety of options for adjusting the properties of the final granules.

An important advantage of cast granules is their environmental friendliness. Unlike traditional wet granulation techniques, the melt granulation process does not require organic or aqueous solvents. This solves environmental problems by eliminating the need to capture and recycle organic solvents. Additionally, the absence of water in the process eliminates the wetting and drying steps, making the overall process less expensive in energy and time.

Melt granulation is a promising alternative for water-sensitive materials as it provides stability to moisture-sensitive drugs while improving the physical properties of the drug substance. However, it is important to recognize the biggest drawback of this process: the high temperatures required during operation. These high temperatures can lead to decomposition and oxidative instability of the components, especially for heat labile drugs.

The choice of binder plays an important role in melt granulation. Choices range from hydrophilic to hydrophobic. The choice of soluble binder with specific hydrophilic or hydrophobic properties becomes an important factor affecting the dissolution behavior of the drug.

When it comes to equipment, high shear mixers and fluidized bed granulators have proven to be key tools to effectively perform melt granulation. Interest in melt granulation has increased significantly in recent years due to its several advantages over conventional wet granulation processes and represents a significant advancement in pharmaceutical manufacturing.

Advantages of Melt Granulation:

  • Controlled release formulations
  • Improved stability
  • Simplified process
  • Shorter processing time
  • Uniform particle size distribution
Controlled release formulations:

Melt granulation is suitable for developing controlled release formulations. Water-soluble binders bind drug particles and enable prolonged, controlled release of the active ingredient.

Improved stability:

The use of water-soluble binders can improve the stability of some active pharmaceutical ingredients (APIs) that may be sensitive to moisture. The absence of water in the granulation process can improve the stability of the final product and extend its shelf life.

Simplified process:

Melt granulation requires fewer processing steps than traditional wet granulation methods, for example no liquid binders are required. This simplification can lead to cost savings and improved production efficiency.

 

Shorter processing time:

The processing time of melt granulation is generally shorter than that of other granulation technologies. The lack of liquid binder and no drying step makes the overall process faster.

Uniform particle size distribution:

Melt granules often produce granules with uniform particle size distribution, which has a positive impact on subsequent processing steps and the overall quality of the final product.

Disadvantages of enamel granulation

  • Difficulty in scaling up
  • Equipment complexity
  • Heat sensitivity
  • Potential API degradation
  • Solubility limitations
Difficulty in scaling up:

Scaling up the fusion granulation process for large-scale manufacturing can be difficult due to the need for specialized equipment and the potential for increased energy consumption. This may limit the scalability of the technology in certain production environments.

 

Equipment complexity:

Handling molten granular materials may require special equipment. This may increase capital costs and limit the accessibility of this technology to some manufacturing facilities.

 

Heat sensitivity:

Molten granules expose the formulation to high temperatures, which may not be suitable for some heat-sensitive drugs or excipients. These limitations may affect the choice of materials for the formulation.

 

Potential API degradation:

Exposure of active ingredients to high temperatures during granulation poses a risk of decomposition of heat-sensitive drugs, potentially impacting the overall quality of the final product.

 

Solubility limitations:

Some excipients or active ingredients may have limited solubility in the fusion binder, limiting the range of formulations that can be successfully formulated using fusion granulation.

Melt granulation offers numerous advantages, including process simplification and reduced processing times, but limitations such as potential heat sensitivity and equipment complexity must be carefully considered when selecting a granulation technique to achieve a specific pharmaceutical formulation. This is important. Calculating.

 

Moisture-Activated Dry Granulation (MADG)

Moisture-activated dry granulation (MADG) technology represents a significant departure from traditional wet granulation methods by using minimal water to trigger binder activation and initiate consolidation. This innovative process consists of two important steps: wet agglomeration of dust particles and subsequent moisture absorption and distribution. For example, consider the use of MADG in the pharmaceutical industry to produce immediate controlled release dosage forms.

In the initial stages of MADG, a small amount of water, typically less than 5% (initial 1-4%), is incorporated into the mixture of drug, binder, and other excipients. This water acts as a granulating fluid, activating the binder and promoting flocculation. Once agglomerated, hygroscopic materials such as microcrystalline cellulose or silica are added to absorb excess moisture. These adsorbents play an important role in redistributing moisture within the powder mixture, resulting in a relatively dry granular mixture. Importantly, this process does not require expensive drying steps and the water consumption is much lower than traditional wet granulation techniques, preventing the formation of larger agglomerates.

During moisture redistribution, some aggregates retain their size, but larger aggregates may break apart, contributing to a more uniform particle size distribution in the 150–500 μm range. Despite the misleading nomenclature, it is important to clarify that MADG is not synonymous with traditional dry granulation techniques, including compression or roll forming. Because MADG uses small amounts of water, the term ‘dry granulation’ was deemed inappropriate and the term ‘wet granulation’ was introduced.

The application of MADG in immediate-release and controlled-release dosage forms has been demonstrated to have many advantages over wet granulation, including larger particle size, improved flow, and improved compressibility. Additionally, MADG has wide applicability, time efficiency, and requires low power consumption. The process involves few process variables and is therefore suitable for continuous processing. However, several limitations exist as MADG is not suitable for high drug loadings and moisture-sensitive or hygroscopic drugs due to associated stability and processing issues.

To expedite the MADG process, a high shear mixer with a nebulizer is recommended as the ideal equipment. These machines should be equipped with efficient impellers, blades and grinders to ensure optimal movement of the mass and correct mixing of the granule mass, contributing to the overall success and efficiency of the technology. The term “MADG (Moisture-Activated Dry Granulation)” was coined by the inventor in 1987 and captures the essence of this innovative pharmaceutical granulation method.

Benefits of Moisture-Activated Dry Granulation (MADG)

  • Energy efficiency
  • Improved drug stability
  • Improved powder flow
  • Reduced water usage
  • Short processing time
Energy efficiency:

MADG often requires lower energy consumption than wet granulation processes, which require significant energy input for drying. Eliminating or reducing drying steps in MADG contributes to energy efficiency and cost savings.

 

Improved drug stability: Because MADG uses less water, it reduces the risk of chemical degradation or hydrolysis of moisture-sensitive drugs, improving drug stability during the granulation process.

Improved powder flow: Water activation of MADG can improve the flow characteristics of granular powder. This is particularly useful in downstream processes such as tablet compression and ensures a smoother, more uniform powder flow during production.

 

Reduced water usage:

MADG typically requires less water than traditional wet granulation processes. This reduction in water consumption is beneficial for moisture-sensitive drugs or formulations where excess moisture may cause performance degradation or instability.

 

Short processing time: MADG has a shorter processing time than wet granulation methods, resulting in higher production efficiency and productivity.

Disadvantages of Moisture-Activated Dry Granulation (MADG)

  • Limited control of granule size
  • Potential for excessive humidity
  • Equipment Sensitivity
  • Scalability challenges
  • Limited applicability
Equipment Sensitivity:

MADG may require special equipment designed to handle moisture activation processes. The sensitivity of equipment to moisture content and different processing conditions can be complex and require precise control and monitoring.

 

Limited applicability:

MADG may not be suitable for all drug formulations or substances. Some drugs or excipients do not respond well to water activation, which may limit the applicability of MADG in certain pharmaceutical manufacturing processes.

 

Limited control of granule size:

Accurate control of granule size in MADG can be difficult compared to wet granulation methods. These limitations can affect the uniformity of the final product, especially in formulations where particle size distribution is important.

 

Potential for excessive humidity:

MADG may be exposed to excessive humidity if moisture content is not carefully controlled. If the humidity is too high, the powder may clump or harden, which will affect the particles and quality of the final product.

 

Scalability challenges: Scaling up the MADG process from laboratory to industrial scale can present challenges in keeping moisture content, particle size, and other critical parameters constant. Ensuring scalability without compromising product quality can be a complex task.

MADG offers numerous advantages, such as reduced water consumption and increased energy efficiency, but also presents challenges related to granule size control, potential for overheating, device sensitivity, scaling issues, and limited applicability of the specific agents attached. Manufacturers should carefully evaluate product characteristics and expected outcomes before selecting MADG with a granular approach.

 

Reverse wet granulation

Reverse wet granulation, also called reverse-phase wet granulation, represents a breakthrough in wet granulation technology. In this innovative method, the dry powder formulation is soaked in a binding liquid and then carefully ground to form granules. The process begins with preparing a binding solution to which dry powder excipients are added during mixing in a granulator. Alternatively, a hydrophilic polymer and/or binder can be mixed with the solution to form a drug-polymer/binder suspension that acts as a granulation fluid. A mixture of different dry excipients is then soaked in the drug polymer/binder suspension to form wet granules, which are dried and then milled.

In practice, a specific example of Reverse wet granulation is the production of pharmaceutical tablets. Using this technology, tablets exhibit improved flow and handling characteristics compared to traditional wet granulation processes. In particular, tablets manufactured by the reverse wet granulation method showed more uniform disintegration in the dissolution test than tablets manufactured by the conventional method. Controlled fracture is the key mechanism of granule formation in Reverse wet granulation, providing a unique method to achieve desired granulation characteristics.

The main reason for the development of Reverse wet granulation is its potential to improve the dissolution properties of poorly soluble drugs. This is achieved by evenly distributing a binder that acts as a wetting agent. Additionally, this technology promotes adequate wetting of the drug during granulation, resulting in better dissolution. In this process, the tight bond between the drug and the hydrophilic polymer increases the likelihood of substantial and uniform contact, which helps improve dissolution characteristics.

Compared with traditional wet granulation, Reverse wet granulation has many advantages. Produces small, round granules with excellent flow properties that ensure uniform wetting and erosion. The close connection between drugs and polymers makes this technique particularly suitable for drugs that are poorly soluble in water. B. You can use readily available equipment, such as high-speed mixers, while also enjoying the convenience and appeal of this innovative granulation method.

Despite its advantages, it is important to note that Reverse wet granulation can produce granules with larger average bulk diameters and fewer intragranular voids than conventional wet granulation, especially at low binder concentrations. These subtleties highlight the need to carefully consider formulation parameters to optimize the process based on specific drug properties and desired outcomes.

 

Advantages of Reverse wet granulation

  • Advanced Ingredient Blending
  • Controlled particle size distribution
  • Minimized exposure to heat and moisture
  • Reduced processing time
Advanced Ingredient Blending:

It involves carefully mixing the active ingredients, excipients and binders and mixing dry powders with liquid binders for uniform distribution. This can improve content consistency in the final product.

Controlled particle size distribution: Counter-wet granulation allows precise control of particle size distribution. This is very important in pharmaceutical manufacturing as particle size can affect the properties of the final product.

Minimized exposure to heat and moisture: Unlike traditional wet granulation methods, Reverse wet granulation minimizes exposure to heat and moisture during the initial mixing stage. This can be useful for heat- or moisture-sensitive active pharmaceutical ingredients (APIs) that may degrade under conventional wet granulation conditions.

 

Reduced processing time:

This process typically involves fewer steps than traditional wet granulation, resulting in shorter processing times and potentially increased production efficiency.

Disadvantages of Reverse wet granulation

  • Application limitations for certain formulations
  • Binder Distribution Issues
  • Potential for dust generation
  • Sensitivity of equipment
  • Susceptibility to separation
Binder Distribution Issues:

Achieving uniform binder distribution in powder mixtures can be difficult, especially for cohesive or low flow powders. Improper binder distribution can cause uneven grain, affecting the quality of the final product.

Application limitations for certain formulations: Rewetting granules may not be suitable for all types of formulations. Some formulations may benefit more from traditional wet granulation methods or other granulation techniques due to the specific properties of the ingredients used.

 

Potential for dust generation:

Dust can be generated during the first dry mixing step of Reverse wet granulation, which can cause problems in terms of handling, control and potential operator exposure. Dust-related issues can also affect the overall cleanliness of the production environment.

 

Sensitivity of equipment:

Processes can be sensitive to the type of equipment used, so selecting the right equipment is important. Special equipment may be required to achieve the desired granule properties, which may increase initial installation costs.

 

Susceptibility to separation:

Some powder mixtures may separate during the mixing and granulation steps, causing fluctuations in granule formation. Minimizing the risk of separation requires careful formulation and process optimization.

 

Reverse wet granulation offers advantages such as controlled particle size distribution and minimal exposure to heat and moisture, but also presents challenges related to dust formation, equipment sensitivity, binder distribution, separation, and limited application of certain formulations. The suitability of Reverse wet granulation depends on the specific requirements and characteristics of the process.

 

Steam granulation

The innovative example of steam granulation, a sophisticated wet granulation technology, departs from the traditional practice of using liquid water as a binder. Instead, the state-of-the-art method uses water vapor as a binder, offering numerous advantages that redefine the granulation process.

In its basic state, vapor represents a transparent gas capable of dispersing dust at high speeds. These unique properties create conditions for an innovative granulation experience together with a more favorable heat balance in the subsequent drying steps. During condensation, the vapor forms a thin, hot film on the dust particles that requires minimal additional energy to remove and evaporates smoothly.

A significant advantage of this innovative technology is the improved ability of vapors to disperse and diffuse evenly through dust particles. The result is spherical particles with a larger surface area, a property that not only increases the dissolution rate but also contributes to the overall efficiency of the process. In particular, this method implements ecological principles by eliminating the need for organic solvents and adapting to sustainable practices.

Implementing this technology in practice requires devices such as high-shear mixers connected to steam generators, highlighting the simplicity and feasibility of integration into existing pharmaceutical or manufacturing facilities. However, it is important to recognize that the energy-intensive nature of steam generation is demanding and requires significant energy input.

Additionally, it is important to note that while steam granulation represents a paradigm shift from wet granulation, it is not a one-size-fits-all solution. This technique is sensitive to thermolabile drugs and may not be universally compatible with all binders. These brief considerations highlight the need for a sophisticated approach to select an appropriate granulation method based on the specific properties of the materials involved.

Using steam as a binder in granulation offers several advantages, including better dispersion, formation of spherical granules, reduced processing time, and respect for the environment. However, the energy requirements and selectivity of this method highlight the importance of tailored applications and careful consideration of compatibility with a variety of materials in pharmaceutical and manufacturing environments.

 

Thermal Adhesion Granulation (TAG)

Wei-Ming Pharmaceutical Company, based in Taipei, Taiwan, has developed an innovative technology called heat bond granulation. This process, similar to wet granulation, is revolutionizing the pharmaceutical industry by using a unique combination of granulating fluids and heat for coagulation.

Unlike moisture-activated dry granulation, which uses only water as the granulation fluid, Wei-Ming technology introduces both water and solvent into the process. Thermal integration plays an important role in promoting the coalescence of dust particles. The mixture of drug and excipients is heated in a closed system in a controlled manner using tumbling rotation while maintaining a temperature range of 30–130°C.

One of the main advantages of this technology is that it does not require a drying process. Efficiency is ensured by adding a minimum amount of granulating liquid, most of which is absorbed into the powder particles during coagulation. After heating, cooling and sieving, granules of the desired particle size can be obtained.

The simplicity and convenience of this method is surprising, especially due to the low moisture and binder content. Because it operates in a closed system, it is very effective in producing highly compressible ingredients or modifying unwanted properties of excipients.

A practical example is the development of new pharmaceutical formulations using heat-adhesive granulation by Wei-Ming. This process produces granules with good particle size, excellent flow properties and high tensile strength. These properties allow direct compression into tablets and ensure that the final product has the required hardness and low brittleness.

However, it is important to recognize the limitations of this technology. Challenges include significant energy consumption and the need for special equipment to generate and control heat. Additionally, this technique is not universally applicable to all binders and is sensitive to heat-labile drugs.

Wei-Ming Pharmaceutical Company’s heat-bonded granulation technology represents a breakthrough in pharmaceutical manufacturing. Although this innovative approach offers numerous benefits, including efficiency, simplicity, and improved product properties, it is important for researchers and manufacturers to consider the limitations associated with it.

Thermal Adhesion Granulation (TAG) is a process used in pharmaceutical manufacturing that uses heat to form adhesive bonds between powder particles, causing granulation. Like any other technology, TAG has its advantages and disadvantages.

 

Advantages of Thermal Adhesion Granulation (TAG)

  • Continuous processing potential
  • Improved flow characteristics
  • Reduced use of excipients
  • Simplified Process
Continuous processing potential:

TAG can be applied in continuous manufacturing processes to improve the scalability and efficiency of pharmaceutical manufacturing.

 

Improved flow characteristics:

TAG can help improve the flow characteristics of granules, making downstream processes such as tablet compression more efficient. Granules produced from TAG tend to have good compressibility and good flow properties.

 

Reduced use of excipients:

Because TAG relies on heat for granulation, it may require fewer excipients or binders than other granulation methods. This may be advantageous for formulations where it is desirable to minimize the use of additional ingredients.

 

Simplified Process:

TAG simplifies the granulation process by often eliminating the need for traditional binders and liquid solutions. This reduces the number of processing steps, making the method simpler and more efficient.

Disadvantages of Thermal Adhesion Granulation (TAG):

  • Changes in particle size
  • Equipment Complexity
  • Energy consumption
  • Limited applicability
  • Temperature sensitivity
Changes in particle size:

Achieving a uniform particle size distribution may be difficult with TAG as particle size may change when heated. This may affect the overall quality and performance of the final formulation.

Energy consumption: The use of heat in TAG requires energy input and the process can be more energy intensive than some alternative granulation methods. These aspects must be considered in terms of economic and environmental sustainability.

 

Equipment Complexity:

Implementing TAG may require specialized equipment to precisely control and apply heat. The initial investment and maintenance requirements for such equipment can increase production costs.

 

Limited applicability:

TAG may not be suitable for all drug formulations or products. The effect may depend on the specific properties of the active pharmaceutical ingredient (API) and excipients used in the formulation.

 

Temperature sensitivity:

TAG requires the application of heat, which can be detrimental to heat-sensitive materials or formulations. Some drugs or excipients may decompose or cause unwanted reactions at high temperatures.

 

TAG offers several advantages:

B. Simplifies the granulation process and potentially reduces the need for excipients; however, it has limitations related to temperature sensitivity, particle size control, equipment complexity, and energy consumption. The choice of granulation method depends on the specific requirements and characteristics of the pharmaceutical formulation.

 

 

Recent advances in dry granulation

Dry granulation, an essential method in pharmaceutical manufacturing, can be performed in two main ways: roller compaction or slugging. Wet granulation has historically surpassed dry granulation in terms of technological advancement and advancement, but significant progress has been made with the pneumatic dry granulation technology developed by Atacama Labs.

Pneumatic Dry Granulation (PDG) features an innovative technology that seamlessly combines roller compaction and a proprietary air fractionation system to produce granules featuring an exceptional combination of flowability and compressibility. In this innovative process, light compression forces are first applied by compression rollers to produce a compact mass consisting of a mixture of fine particles and granules. The fractionation chamber then uses a pneumatic system to separate fine and small particles from particles of the desired size.

Once particles of the desired size pass through a fractionation chamber and are compressed into tablets, the accompanying fine and small particles are sent to a cyclone-like device. This is where you come across an important decision point. Immediate reprocessing through recycling or reprocessing in roller compactors or storage in the desired granular form for subsequent reprocessing.

The versatility of PDG technology is evident as it has proven adept at producing well-flowing granules for a variety of formulations to produce compact products with tensile strengths of approximately 0.5 MPa. Additionally, compared to conventional roller compaction processes, this technology offers the advantage of high active material loadings of around 70 to 100%, as noticeable smoothness can be achieved even at low roller compaction forces (low solids content).

In addition to the benefits of smoothness, PDG technology offers many additional benefits, including accelerated processing speeds, cost-effectiveness, minimal material waste, and reduced dust due to the drive’s closed design. However, despite these advantages, several challenges remain, such as the impact of recycling on granule quality, compatibility with low-volume formulations, and fragility issues.

Pneumatic dry granulation technology not only represents a significant advance in dry granulation engineering, but also an innovative solution that has the potential to transform pharmaceutical manufacturing processes with the potential to deliver higher efficiency, lower costs and better product quality. represents .

Aerodynamic dry granulation is a pharmaceutical manufacturing process that forms granules without the use of liquid binders. A roller compactor is used to apply compressive force to the dry powder particles and then reduce them to pulverized size. Like any other technology, pneumatic dry granulation has advantages and disadvantages.

  • Advantage
  • Binder-free process
  • Cost savings
  • Faster processing
  • Uniform granule size
Binder-free process:

Pneumatic dry granulation does not require liquid binders, making it suitable for moisture-sensitive materials. The result is a final product with increased stability and durability.

Cost savings: By eliminating the purchase, storage and disposal of liquid binders, pneumatic dry granules can reduce costs on raw materials and related processing steps.

 

Faster processing:

This process is generally faster than wet granulation methods because it does not require the drying time associated with liquid binders. This can help increase productivity and efficiency in pharmaceutical manufacturing.

 

Uniform granule size:

Aerodynamically, dry granulation can produce granules with uniform size and distribution. This uniformity is important to ensure consistent drug content and potency in the final dosage form.

Disadvantage

  • Dust generation
  • Equipment Complexity
  • Energy consumption
  • Limited powder flow characteristics
  • Tablet hardness issues
Dust generation:

Fine dust particles or dust may be generated due to drying of the process. Dust control is essential to maintain a safe working environment and prevent cross-contamination between batches.

 

Equipment Complexity:

Pneumatic dry granulation usually requires the use of special equipment such as roller compactors and mills. The initial investment and maintenance costs of these devices can be expensive.

Energy consumption: Roller compaction requires energy to utilize the compaction force and the overall energy consumption of the process must be considered. However, the goal of technological advancements is to optimize the energy efficiency of pneumatic dry granulation systems.

 

Limited powder flow characteristics:

The properties of the powder material can affect the success of dry pneumatic granulation. Materials with poor flow characteristics may not compress efficiently and may have difficulty achieving the desired particle size.

 

Tablet hardness issues:

It can be difficult to achieve the desired tablet hardness without using liquid binders. Additional steps or process changes may be required to ensure that the tablets have the required mechanical strength.

Dry pneumatic granulation offers many advantages, especially in terms of binder absence, speed and uniformity. However, challenges such as dust generation and tablet hardness must be carefully addressed and methods selected based on the specific properties of the material to be processed and the desired properties of the final product.

 

Choosing a Wet Granulation Method

The choice of wet granulation method depends on the specific characteristics of the product to be manufactured, the desired characteristics of the final granulation, and the efficiency and cost-effectiveness of the process. We briefly discuss each approach and provide examples where appropriate.

 

  • Freeze granulation
  • Foam Granules
  • Melt granulation
  • Moisture-activated dry granulation (MADG)
  • Reverse-wet granulation
  • Steam granulation
  • Thermal Adhesion Granulation (TAG)
Freeze Granulation:

The process involves precipitating a liquid binder into a powder mixture.
Example: In the ceramics industry, freeze-drying can be used to produce granules for the production of high-performance ceramics with improved sintering properties.

Foam Granulation:

Liquid or water-based binders are added into the foam to improve binder distribution.
Example: In the pharmaceutical industry, foam granulation can be useful to produce tablets with consistent drug release profiles and better reproducibility.

 

Melt Granulation:

Granulation occurs by dissolving the binder, which solidifies upon cooling.
Example: The plastics industry can use melt granulation to produce polymer granules of controlled size and shape.

Moisture-activated dry granulation (MADG):

This method involves dry granulation followed by water activation for agglomeration.

Example: In detergent production, moisture-activated dry granulation can produce free-flowing granules that are easy to handle and package.

 

Reverse-wet granulation:

In this method, the powder is wetted with a liquid binder after the dry mixing step is initiated.

Example: Pharmaceutical tablet formulations where the active pharmaceutical ingredient (API) is sensitive to moisture and binders must be added carefully after initial mixing.

 

Steam granulation:

The use of steam conditions causes dust particles to coagulate.
Example: Steam granulation can be used in the fertilizer industry to produce granules with improved flow characteristics and reduced dust.

 

Thermal adhesion Granulation (TAG):

With TAG, heat is applied to create the adhesion needed to form granules.
Example: TAG can be used in the food industry to granulate ingredients in the production of grain products to improve texture and flavor.

The choice of the most appropriate method depends on factors such as product type, required granularity, sensitivity of the material, and overall efficiency of the production process. For example, in the pharmaceutical industry, foam granulation may be preferred for drugs that are more sensitive to wetting, while steam granulation may be applied in fertilizer production to improve the fluidity of granules. It is important to carefully consider the specific requirements of each product and the benefits offered by each granulation method.

Granulation Method Advancements Read More »

What is Lean Six Sigma?

What is Lean Six Sigma?, Lean Six Sigma is an approach that combines two powerful process improvement methods: Lean and Six Sigma. Although both originated in the manufacturing sector, they are widely used in a variety of industries to increase efficiency, reduce defects, and improve overall performance.

  • Lean
  • Six Sigma
Lean:

Lean focuses on increasing efficiency by eliminating waste and optimizing processes. It is derived from the Toyota Production System and aims to maximize customer value while minimizing waste. Key principles include identifying and eliminating non-value-added activities, reducing lead times, and optimizing resource use.

Lean, a management philosophy based on the principles of efficiency and continuous improvement, is committed to increasing efficiency by eliminating waste and improving processes. This approach is derived from the Toyota Production System, an innovative approach in the automotive industry that has become the standard for organizational excellence.

Fundamentally, Lean pursues the ultimate goal of maximizing customer value and minimizing waste. The emphasis on customer value is reflected in the continuous effort to achieve greater satisfaction by providing products or services that closely match customers’ expectations. Waste reduction, a core principle of Lean, involves identifying and eliminating activities that do not add value within a production or service process.

 

Notable examples of implementing Lean principles can be seen in the manufacturing sector, particularly on automotive assembly lines. Toyota, the originator of lean thinking, has implemented a variety of lean strategies in its production lines. One of the key practices is to systematically identify and eliminate steps or activities that do not directly contribute to the value of the final product from the customer’s perspective. This includes eliminating excess inventory, reducing unnecessary material movement or transportation, and optimizing the use of manufacturing resources.

 

Reducing delivery times is another important aspect of Lean. This includes streamlining processes to reduce the time between process start and completion. For example, in a lean manufacturing environment, the time from receipt of a customer order to delivery of the finished product is carefully considered and shortened where possible, resulting in faster, more customer-centric operations.

 

Lean also attaches great importance to optimizing resource use. This includes using all resources, including labor, materials and equipment, efficiently and without waste. For example, a lean healthcare organization might focus its efforts on reducing patient waiting times, optimizing the use of medical equipment, and using staff time effectively to improve patient care.

That said, Lean’s multifaceted approach, based on the Toyota Production System that promotes a culture of continuous improvement, customer focus, and resource efficiency, finds fertile ground in a variety of industries. By adopting Lean principles, companies can not only optimize their processes, but also increase overall customer satisfaction and lay the foundation for sustainable operational excellence.

 

Six Sigma:

Six Sigma is a data-driven methodology that aims to reduce errors and process variation. Six Sigma was developed by Motorola and popularized by companies such as General Electric. The goal is to achieve high quality and consistency.

This includes the Define, Measure, Analyze, Improve and Control (DMAIC) process to ensure that customer expectations are met or exceeded.
Six Sigma represents a powerful, data-driven approach designed to systematically reduce errors and reduce process variation. Originally conceptualized by Motorola and later promoted by industrial giants such as General Electric, Six Sigma focuses on achieving high levels of quality and consistency in organizational processes.

This approach is based on a systematic and comprehensive approach called DMAIC (Define, Measure, Analyze, Improve and Control). Each step plays a fundamental role in the continuous improvement journey and ensures that the process is fully aligned with customer expectations and company goals.

Define:

At this stage, the project objectives, scope, and stakeholder requirements are clearly formulated. This forms the basis of the overall improvement plan and ensures a focused and targeted approach.

Example: In a manufacturing environment, the definition phase may involve identifying specific product defect issues, such as irregularities in critical component dimensions that negatively impact the overall quality of the product.

Measure:

Metrics and data are collected to measure the current state of the process. This includes understanding baseline performance and identifying areas requiring improvement.

Example: Using statistical tools, measurements are taken to assess changes in the levels of the above elements, providing a quantitative understanding of existing quality levels.

 

Analyze:

In this step, the collected data is analyzed to identify root causes of errors and inconsistencies. Statistical methods are used to identify specific factors that affect process performance.

Example: Statistical analysis shows that temperature fluctuations during the manufacturing process significantly affect the dimensional variation of a material.

 

Improve:

Based on the analysis, improvements and optimizations are implemented to address the root causes identified. The purpose of this step is to improve the process and eliminate sources of error.

Example: Implementing a controlled environment with controlled temperature settings during the manufacturing process to reduce material dimensional variations.

 

Control:

The final step focuses on defining control and monitoring processes to maintain improvements over time. This ensures that your processes are consistently reliable and always meet or exceed customer expectations.

Example: Implement regular quality checks and integrate a real-time monitoring system to maintain a controlled production environment and prevent recurrence of dimensional errors.

 

Through the DMAIC framework, Six Sigma provides a structured path for continuous improvement that not only solves existing problems but also leads to sustainable, high-quality results that meet customer expectations and business goals. The success of this approach lies in its commitment to data-driven decision making and a systematic approach to process improvement.

 

Integration of Lean and Six Sigma:

Lean Six Sigma combines Lean and Six Sigma principles to provide a comprehensive approach to process improvement. The goal is to minimize defects and provide high-quality products or services through efficient processes. Lean tools are used to eliminate waste and simplify processes, while Six Sigma tools are used to reduce variation and errors.

Lean Six Sigma is a holistic approach that combines the fundamental principles of Lean and Six Sigma to create a powerful framework for systematic and sustainable process improvement. The overall goal is to optimize product or service delivery by ensuring high quality, minimizing errors, and promoting efficiency in operational processes.

Basically, Lean Six Sigma leverages the strengths of Lean, which is based on the pursuit of efficiency and reducing waste, and Six Sigma, which focuses on accuracy and error reduction. By integrating these methods, companies pursue a balanced and comprehensive approach to process improvement.

  • Lean Contributions
  • Six Sigma Contributions
  • Practical Integration
  • Culture of continuous improvement
Lean Contributions:

Derived from the Toyota Production System, Lean focuses on identifying and eliminating activities that do not add value. Tools such as value stream mapping (VSM) allow companies to gain insight into their entire process flow, allowing them to identify and eliminate inefficiencies. For example, in a manufacturing environment, lean principles may include optimizing production line layout, reducing excess inventory, reducing unnecessary work movement, etc., which can ultimately lead to streamlining operations.

 

Six Sigma Contributions:

Developed by companies such as Motorola, Six Sigma focuses on statistical analysis to reduce variability and errors in processes. For example, Six Sigma tools can be used to analyze data about document errors, turnaround times, or customer satisfaction scores in transaction processes within a financial institution. By identifying root causes and implementing data-driven solutions, Six Sigma ensures more consistent and error-free results.

 

Practical integration:

Imagine a healthcare organization adopting Lean Six Sigma to improve patient care processes in a real-world scenario. Lean tools can help you optimize the patient journey, reduce wait times, reduce unnecessary steps, and improve the overall flow within your facility. At the same time, Six Sigma methods will be used to analyze medical errors, standardize treatment protocols, and reduce variability in clinical outcomes to ensure high-quality treatment.

 

Culture of continuous improvement:

A key part of Lean Six Sigma is the continuous improvement concept known as Kaizen. This includes creating a culture where teams regularly evaluate processes, collect feedback, and implement incremental changes. By adopting Kaizen, companies ensure that the gains achieved through Lean Six Sigma are maintained over time and adaptable to changing business needs and customer expectations.

Simply put, Lean Six Sigma provides a comprehensive and dynamic framework for companies looking to improve performance. By combining the efficiency-based principles of Lean with the precision-based techniques of Six Sigma, companies can achieve the twin goals of delivering high-quality products or services while maintaining optimal process efficiency and minimizing defects. there is. This integration fosters a culture of continuous improvement and helps companies succeed in today’s competitive and rapidly evolving business environment.

 

Key elements of Lean Six Sigma:

DMAIC: Define, Measure, Analyze, Improve, and Control is a structured approach to problem solving used in Lean Six Sigma projects.
The DMAIC methodology, which includes define, measure, analyze, improve and control, is the cornerstone of the Lean Six Sigma framework and serves as a structured problem-solving approach needed to achieve process excellence. Each stage of DMAIC is carefully designed to guide an organization through a systematic journey of identifying problems, measuring performance, analyzing root causes, implementing improvements, and establishing controls.

For example, let’s say a manufacturing company is implementing DMAIC to improve its manufacturing process. During the definition phase, organizations can establish specific goals such as reducing defects, improving cycle times, and improving product quality. In the “Measure” phase, companies quantitatively assess the current state of their processes by collecting relevant data on error rates, cycle times, and other key performance indicators.

Value Stream Mapping (VSM): A technique used in Lean to visualize and analyze the steps required to deliver a product or service to identify areas for improvement.
Value Stream Mapping (VSM), a foundational technology of Lean, complements the DMAIC approach by providing a visual representation of the end-to-end process of product or service delivery. Let’s look at a real-life example from the healthcare industry. Hospitals can use VSM to map the patient journey from admission to discharge. This visualization helps you identify bottlenecks, delays, or unnecessary steps, paving the way for improved goals.

Kaizen: Japanese for “continuous improvement” and emphasizes the philosophy of making small, incremental improvements over time.
In the spirit of continuous improvement, kaizen, a Japanese word meaning “continuous improvement,” emphasizes small, incremental changes over time. Real-world examples of application can be found in software development companies where teams regularly participate in Kaizen events to improve coding practices, collaboration, and project management methods.
Statistical Tools: Six Sigma uses statistical methods to analyze and improve processes such as control charts, histograms, and regression analysis.
Lean Six Sigma Statistical tools play an important role in the Six Sigma approach. Businesses often use control charts, histograms, and regression analysis to identify patterns, trends, and deviations in their processes. For example, financial institutions implementing Six Sigma can use statistical tools to analyze transaction data, identify outliers, and streamline processes to reduce errors and increase accuracy.

Companies use Lean Six Sigma to increase efficiency, reduce costs, increase customer satisfaction, and achieve sustainable performance improvement. This applies to a variety of industries including manufacturing, healthcare, finance, and services.

The overall goal of Lean Six Sigma is to enable companies to increase efficiency, reduce costs, and increase customer satisfaction through sustainable performance improvement. The versatility of this approach is evident across a variety of industries, including manufacturing, healthcare, finance, and services. Because it provides a comprehensive and adaptable framework for achieving operational excellence for continuous improvement in all aspects of a company’s operating organization.

 

What are the main differences between Lean Six Sigma and Six Sigma?

Although Lean Six Sigma and Six Sigma are related methods, there are important differences between them. The main differences are:

  • Philosophy and origin
  • Opportunities for improvement
  • Waste management
  • Tools and techniques
  • Customer orientation
  • Implementation speed

 

Philosophy and origin:

Six Sigma: Six Sigma was created by Motorola in the 1980s and popularized by companies such as General Electric. It primarily focuses on reducing errors and process variation. The goal is to achieve a high level of quality and consistency using statistical methods and a structured approach to problem solving (DMAIC: Define, Measure, Analyze, Improve, Control).

Lean Six Sigma: While Six Sigma focuses on quality, Lean Six Sigma combines the principles of Six Sigma and Lean. Lean is derived from the Toyota Production System and focuses on eliminating waste and optimizing processes. Incorporating lean principles improves the efficiency and flow of processes and reduces errors.

 

Opportunities for improvement:

Six Sigma: Focuses primarily on reducing errors and changing processes. Waste and process flow issues cannot be addressed as comprehensively as Lean.
Lean Six Sigma: Expands beyond error reduction to eliminate waste, reduce cycle times, and optimize overall processes. It covers both quality and efficiency aspects of the process.

 

Waste management:

Six Sigma: Does not explicitly focus on eliminating different types of waste from processes.
Lean Six Sigma: Explicit integration of Lean principles to identify and eliminate various types of waste, such as overproduction, waiting time, unnecessary transportation, overprocessing, excessive inventory, and errors.

 

Tools and techniques:

Six Sigma: Relies heavily on statistical tools and techniques for data analysis and problem solving.
Lean Six Sigma: Six Sigma integrates both statistical tools and lean tools such as value stream mapping (VSM) and 5S to eliminate waste and optimize processes.

 

Customer orientation:

Six Sigma: Meeting customer specifications and expectations primarily by reducing defects.
Lean Six Sigma: Expands focus on increasing customer value by not only delivering defect-free products but also optimizing processes for efficiency and responsiveness to customer needs.

 

Implementation speed:

Six Sigma: Changes and improvements may take longer to implement.
Lean Six Sigma: Emphasizes rapid implementation of improvements, particularly through the Lean philosophy of continuous flow and minimal delay.

Basic Principle of Six Sigma

In summary, while Six Sigma focuses on improving quality and reducing errors, Lean Six Sigma combines this with Lean principles to create a more comprehensive approach that considers both quality and efficiency aspects of the process, a powerful approach for overall business improvement. Create a way.

What is Lean Six Sigma? Read More »

Basic Principle of Six Sigma?

Basic principle of Six Sigma, Six Sigma is a set of process improvement techniques and tools first developed by Motorola in the 1980s. The basic principles of Six Sigma aim to reduce defects, improve quality, and improve overall business processes. The basic principles of Six Sigma are:

  • Customer focus
  • Data-driven decision making
  • Process improvement
  • DMAIC methodology
  • Reduce deformation
  • Leadership Participation
  • Employee engagement and training
  • Project-based approach
  • Statistical tools and techniques
  • Continuous monitoring and control
Customer focus:

Identify and understand customer needs. Define processes aimed at meeting customer needs and expectations.

To be successful and increase customer satisfaction, it is important for businesses to carefully identify and understand their customers’ individual needs. It’s about going beyond superficial expectations and exploring the deep, often unexpressed needs and preferences of your customer base. A comprehensive understanding of customer requirements allows companies to seamlessly adapt products, services, and processes to customer expectations.

To effectively implement this policy, companies can adopt a variety of strategies, including conducting in-depth market research, customer surveys, and conducting feedback processes. For example, a technology company looking to improve customer experience can conduct surveys and interviews to discover not only the functional requirements of its products, but also the emotional aspects that contribute to customer satisfaction. This may include user interface preferences, responsiveness, and overall user experience.

Once customer needs are identified, the next important step is to define and structure processes within the organization focused on meeting those needs. This requires strategic alignment of internal workflows, resource allocation, and quality standards to clearly align with customer expectations. This can be applied in practice in the hospitality industry, where hotels carefully design their service delivery processes to meet different customer preferences. From the check-in process to in-room amenities to personalized service, every aspect of the guest experience is designed to meet or exceed guests’ expectations.

This customer-centric approach also requires continuous monitoring and flexibility to adapt processes to changing customer requirements. For example, e-commerce platforms can use data analytics to continuously analyze customer behavior and preferences. Taking into account ever-changing trends and customer feedback, the platform improves processes such as website navigation, product recommendations, and customer support to ensure it continues to meet and exceed customer expectations in a dynamic market.

In other words, identifying and understanding customer needs is the foundation of a company’s success. Achieving these goals requires a multifaceted approach that includes market research, customer engagement, and continuous process improvement. By proactively designing processes around customer needs, companies can build a solid framework for sustainable customer satisfaction and loyalty.

 

Data-driven decision making:

Use data and statistical analysis to make informed decisions. Use data to understand and improve your processes rather than relying solely on intuition.

In the Six Sigma realm, a fundamental principle is that decisions should be based on concrete evidence and statistical analysis, avoiding the problems that arise when relying solely on intuition. This includes harnessing the power of data as a compass for organizational navigation and strategic improvement. The emphasis on data-driven decision-making highlights the importance of deriving meaningful insights from empirical observations to inform and guide action.

In real-world situations, companies often face complex problems, one of which is the manufacturing sector. Imagine a production line where defects are constantly occurring in the final product. Intuition may suggest possible causes, but the actual cause of the problem may still be elusive. However, by collecting and analyzing data from various stages of the manufacturing process, Six Sigma professionals can pinpoint specific problem areas, identify patterns of variation, and unravel a complex web of error sources.

For example, you can use statistical tools such as control charts to track variations in a manufacturing process over time. By examining data trends, anomalies, and correlations, companies can gain a deeper understanding of the factors that impact product quality. This data-driven approach not only eliminates the guesswork, but also provides a solid foundation for implementing targeted improvements.

In essence, information dependence is about more than just decision making. Be a catalyst for continuous improvement. By understanding the complexity of the process from a statistical perspective, companies can proactively initiate changes that increase efficiency, reduce errors, and ultimately increase customer satisfaction. The shift from insight-driven decision-making to a data-driven paradigm demonstrates the transformative impact Six Sigma approaches have on organizational performance and highlights the effectiveness of powerful, evidence-based technologies in achieving operational excellence.

 

Process improvement:

Continuous efforts to improve processes. Identify and eliminate sources of deviations and errors in the process.

Building a culture of continuous process improvement is essential to continuously pursue organizational excellence. This requires a dynamic and continuous effort to identify, analyze and improve various aspects of operational processes. A key aspect of this project is to systematically identify and eliminate sources of deviations and errors in these processes, with the ultimate goal of achieving greater efficiency, consistency and customer satisfaction.

For example, consider a manufacturing company that produces electronic components. We regularly evaluate the manufacturing processes involved in PCB assembly while looking for process improvements. By carefully monitoring the production line, we identify deviations in the welding process that lead to defects such as incomplete connections or misalignment.

To solve this problem, the company implemented a Six Sigma initiative and used statistical tools to analyze data related to the welding process. Through rigorous measurement and analysis, we identify specific variables that contribute to deviations and errors. This may be caused by temperature fluctuations during welding or compatibility issues with the welding equipment.

Based on this knowledge, the company makes targeted improvements. They invest in temperature control systems, maintain welding equipment, and provide additional training to operators. This means that error-causing deviations are systematically addressed and eliminated. Overall PCB quality is improved and defects are significantly reduced, making the manufacturing process more robust.

This real-life example highlights the importance of not only recognizing the need for continuous process improvement, but also actively engaging in a structured approach to identifying and eliminating sources of deviations and errors. These activities not only improve the reliability and quality of the product or service, but also contribute to the company’s overall competitiveness and success in the market.

 

DMAIC methodology:

DMAIC stands for Define, Measure, Analyze, Improve and Control. A structured problem-solving method used in Six Sigma. Define project issues and goals, measure current performance, analyze data to identify root causes, improve processes, and audit improved processes to ensure sustainability.
DMAIC, an acronym that summarizes the key steps of “Define, Measure, Analyze, Improve and Control,” serves as the foundation of the Six Sigma methodology, a systematic, data-driven approach to process improvement. Let’s look at each step with real examples to understand what they mean.

  • Define
  • Measure
  • Analyze
  • Improve
  • Control
Define:

In this initial phase, the organization clearly articulates the problem at hand and sets project goals. By clearly defining the scope, boundaries, and goals, your team can accurately understand the challenges it will face.

Example: A manufacturing company discovered recurring defect issues in a particular product line, resulting in increased customer complaints and warranty claims. The “Define” phase involves describing the problem in detail, including defect type, frequency, and impact on customer satisfaction.

 

Measure:

Once the problem is defined, the focus shifts to measuring the current state of the process. Measurable indicators are used to evaluate performance and identify key areas for improvement.

Example: In a manufacturing scenario, teams measure defect rates, production cycle times, and other relevant metrics. Accurate measurements provide a basic understanding of current performance levels and form the basis for subsequent analysis.

 

Analyze:

The analysis phase aims to use measured data to find the root cause of the identified problem. Statistical tools and methods are used to analyze patterns and relationships in data.

Example: Statistical analysis may reveal that variations in raw material quality contribute significantly to errors. These insights help your team focus on addressing the root cause rather than simply treating the symptoms.

 

Improve:

Based on the analysis, improvement steps include the development and implementation of solutions to address the identified root causes. The goal is to optimize processes and increase performance based on the knowledge gained.

Examples: Implementing a better quality management system, reviewing supplier selection criteria, and improving manufacturing equipment are potential improvements to address the root causes of defects in a manufacturing scenario.

 

Control:

The final step, control, ensures that the improvements achieved are maintained over time. Control measures, including standard operating procedures and ongoing monitoring, are in place to prevent problems from recurring.

Examples: Conducting regular quality checks, establishing ongoing training programs, and incorporating feedback loops for continuous improvement are steps taken during the control phase. These actions will help you maintain progress during the improvement process.

By systematically going through these DMAIC steps, organizations can not only solve specific problems, but also build a culture of continuous improvement to ensure sustainable excellence in processes and results.

 

Reduce deformation:

Reduce process variation to achieve consistency and predictability of results. Control the factors that contribute to change to achieve more consistent and reliable results.

Reducing process variation is a critical effort to achieve organizational excellence because it improves consistency and predictability of results. By systematically controlling the factors that contribute to change, companies can create an environment where operations are more stable and results consistently align with desired goals. Let’s explore these principles in more detail through a real-world example.

Imagine a manufacturing company that produces electronic components used in a variety of applications. The company recognizes process diversity as an important challenge in meeting quality standards and customer expectations. An important aspect of the manufacturing process is soldering the components to the printed circuit board.

To solve this problem, companies apply Six Sigma methods to reduce process variability. They analyze data from the welding process and identify key factors contributing to changes in solder joint quality, including: B. Temperature fluctuations, operating technology and device settings. By fully understanding these variables, companies can systematically control and optimize them.

For example, companies install temperature control systems to minimize fluctuations in soldering temperature. Provide workers with in-depth training in standardized welding techniques to ensure consistency across the production line. We also implement an equipment maintenance program to ensure machines are operating at optimal settings.

As a result of these efforts, the manufacturing company experienced a significant reduction in process variation. Welded connections consistently meet or exceed quality standards, resulting in more predictable and reliable manufacturing processes. This means that the electronic components supplied are of better quality and adhere more accurately to specifications, resulting in higher customer satisfaction.

In short, reducing process variation by systematically controlling contributing factors is not simply a theoretical principle, but a practical necessity for organizations pursuing excellence. A real-life example from a manufacturing company demonstrates how Six Sigma methods can be applied to achieve consistency, predictability, and reliability in operational results, ultimately contributing to overall business success.

 

Leadership Participation:

Leadership plays a critical role in the success of any Six Sigma initiative. Management commitment and active participation are essential to creating a culture of continuous improvement.
Effective leadership is critical to the success of a Six Sigma initiative and acts as a lever to drive an organization’s success toward continuous improvement. Executive commitment and active participation are not just enablers, but the cornerstone for instilling and sustaining a culture that thrives on continuous improvement.

Let’s imagine a manufacturing company that has decided to implement Six Sigma methods to actually improve product quality. Leadership teams, starting with senior management, recognize the need to adopt Six Sigma principles. Their commitment goes beyond just formal service. Provides financial and human resources to support Six Sigma projects.

Leaders actively collaborate with Six Sigma teams to provide guidance, remove obstacles, and emphasize the importance of the initiative at all levels of the organization. It conveys the strategic importance of Six Sigma in achieving overall business goals and meeting customer expectations.

Managers also instill a spirit of continuous improvement in employees by modeling desired behaviors. Participate in training programs, prominently advocate and support Six Sigma methodology, and celebrate positive project results. This commitment creates far-reaching effects and fosters a culture where all employees are not only empowered but committed to contributing to continuous improvement efforts.

In these situations, leadership commitment is not a one-time announcement but a sign of ongoing support. They establish systems for regular communication about Six Sigma progress, celebrate successes, and address any challenges transparently. This consistent integration makes it clear to the entire organization that Six Sigma is not a temporary initiative, but a core part of the company’s identity.

The impact of leadership in this context is profound. This sets the tone for organizational behavior and influences how employees perceive and embrace Six Sigma. When leaders prioritize and actively participate in Six Sigma initiatives, they become an integral part of the company’s DNA and create a sustainable culture of continuous improvement that goes beyond specific projects and becomes the way we do business.

 

Employee engagement and training:

Engage and empower employees at all levels of the organization. Provide training to ensure staff have the skills necessary to contribute to improvement efforts.

Engaging and empowering employees at all levels within an organization is a key aspect of fostering a culture of continuous improvement. By actively involving employees in the decision-making process and empowering them to contribute to various aspects of the organization’s operations, companies can gain diverse perspectives and skills. This integrated approach not only boosts morale but also fosters a sense of belonging and commitment among employees.

A specific way to implement this policy is through extensive training programs. By providing the necessary skills and knowledge, employees can become active participants in process improvement initiatives. This training can cover a wide range of concepts, from technical skills relevant to a specific role to problem-solving methods and statistical analysis techniques. For example, a manufacturing organization may provide training in quality control procedures, while a service-oriented organization may focus on improving customer service and communication skills.

A specific example is the Toyota production method, which is considered a precursor to Six Sigma. Toyota places great emphasis on employee engagement and empowerment. Team members are encouraged to actively participate in identifying and reporting problems, as well as proposing and implementing solutions. This approach has been a key element of Toyota’s success and has contributed to its reputation for efficiency, quality and innovation.

Additionally, technology companies such as Google and Microsoft place great importance on continuous learning and development. Provide opportunities for your employees to continually train and improve their skills, ensuring your workforce can adapt and contribute to the evolving technological environment. This investment in employee empowerment not only contributes to individual career growth, but also to the overall success and innovation of the company.

Simply put, engaging and empowering employees through comprehensive training not only strengthens individual capabilities but also promotes a collaborative and innovative organizational culture. Examples of this approach include successful companies that recognize the enormous potential of their employees and actively invest in their further development, ultimately contributing to sustainable process improvement and organizational success.

 

Project-based approach:

Six Sigma projects are typically undertaken to solve a specific problem or improve a specific process. Projects are selected based on customer satisfaction and potential impact on overall business goals.

Six Sigma projects are carefully designed strategic initiatives to solve a specific challenge or optimize a targeted process within an organization. These projects are carefully selected based on in-depth analysis of their potential impact on both customer satisfaction and overall business goals.

In real-world situations, companies often initiate Six Sigma projects to improve the quality of their products or services and meet or exceed customer expectations. For example, imagine a manufacturing company that has discovered recurring defects in its product line based on customer feedback and internal quality ratings. In response, the company launched a Six Sigma project focused on eliminating the root causes of defects to improve overall product quality and reliability.

Six Sigma project selection is a strategic decision-making process that comprehensively evaluates factors such as the importance of the problem, potential impact on customer experience, and alignment with broader business goals. For example, a financial institution can undertake a Six Sigma project to streamline the loan approval process by addressing specific bottlenecks. Optimizing this can significantly increase customer satisfaction by reducing processing times.

By aligning Six Sigma projects with customer-centric goals and broader business goals, companies can not only solve immediate problems, but also contribute to long-term sustainability and competitiveness. This approach ensures that improvements achieved through Six Sigma initiatives are strategic improvements that align with the company’s overall goals and vision, rather than individual solutions.

 

Statistical tools and techniques:

Six Sigma uses statistical methods to analyze data and make informed decisions. Common statistical tools include control charts, histograms, regression analysis, and capability analysis.
Six Sigma, a widely used process improvement methodology, emphasizes using statistical methods to analyze critical data and promote informed decision-making within organizations. This strategic approach is critical to identifying areas for improvement, reducing errors, and improving overall operational efficiency. Integrating statistical tools into the Six Sigma framework provides a systematic, data-driven way to understand, control, and optimize various processes.

The main statistical tool used in Six Sigma is the use of control charts. These graphs allow companies to monitor process variations over time to detect early deviations from desired performance. For example, during manufacturing, control charts can track the dimensions of a product to ensure it always meets certain standards. If inconsistencies suddenly increase in the graph, a proactive response is initiated to investigate and resolve the underlying problem before it becomes a defect or quality issue.

Histograms are another valuable statistical tool in the Six Sigma toolkit. Graphical representations of these data distributions help companies visualize and understand the frequency and patterns of variation within their processes. For example, customer service can use histograms to analyze customer response times. Using histogram analysis to identify and resolve outliers or trends can help you improve service efficiency and customer satisfaction.

Regression analysis is used to understand the relationships between variables and their impact on the outcome of a process. For example, in the healthcare industry, Six Sigma experts can use regression analysis to determine factors that affect patient waiting times. By identifying and accounting for key variables like scheduling and staffing, healthcare providers can streamline processes, reduce wait times, and improve the overall patient experience.

Capability analysis is a statistical tool for evaluating how well a process meets specified requirements. For example, in the context of software development, process capability analysis can be applied to assess the consistency and accuracy of the coding process. By analyzing and improving the performance of coding processes, companies can reduce errors, improve software quality, and more effectively meet customer expectations.

Fundamentally based on statistical methods, Six Sigma allows companies to transform raw data into actionable information. This makes it easier to identify inefficiencies in your processes as well as implement targeted improvements, improving overall performance and customer satisfaction.

Continuous monitoring and control:

Monitor processes and establish controls to ensure long-term improvements and implement control plans to prevent errors or inconsistencies from recurring.

Building control mechanisms represent the basic steps of the Six Sigma approach, which aims to carefully monitor processes to ensure long-term sustainability of improvements. These controls act as vigilant safeguards, ensuring that hard-won improvements in operational efficiency and product quality are maintained over time. To reinforce this commitment to sustainable excellence, companies implement robust control plans designed to proactively respond if potential defects or deviations in their processes recur.

A specific example of the importance of control and planning processes can be found in the manufacturing sector. Consider a company that has successfully applied Six Sigma to improve the manufacturing of key components of its products. The DMAIC process identified and eliminated inefficiencies, reduced defects, and optimized manufacturing processes.

To ensure the sustainability of these improvements, the company is currently putting in place control systems such as real-time monitoring of key process parameters, regular audits and statistical process control charts. These processes act as a continuous monitoring system and immediately report any deviations from the optimized process.

At the same time, the organization develops and implements a comprehensive control plan. These plans describe preventive actions and responses to potential problems and serve effectively as a proactive defense strategy. For example, if a particular machine parameter reaches a critical threshold, the control plan may require immediate adjustments, preventive maintenance, or temporary production interruption to investigate and address the root cause.

What is Six Sigma?

By carefully adhering to these principles and the DMAIC methodology, organizations ensure that the improvements achieved are permanent changes, not temporary wins. A combination of careful monitoring and preventative control planning helps create a culture of continuous improvement and a dynamic, adaptive environment where the pursuit of quality and efficiency is rooted in the company’s DNA. This holistic approach not only reduces the risk of process slowdowns, but also provides a sustainable path for companies to improve overall business performance. This is all about the Basic principle of Six Sigma.

Basic Principle of Six Sigma? Read More »

What is Six Sigma?

What is Six Sigma?, Six Sigma is a systematic, data-driven approach and method for eliminating defects (aiming for six standard deviations between the mean and the nearest specification limit) in all processes, from manufacturing to trading, products to services. It was developed by Motorola and popularized by General Electric (GE) in the mid-1980s.

The main goal of Six Sigma is to reduce the variability of manufacturing and business processes, identify and eliminate the causes of defects, and improve the quality of process results. This approach uses a set of statistical and quality control tools, such as DMAIC (Define, Measure, Analyze, Improve, Control) or DMADV (Define, Measure, Analyze, Design, Verify), to systematically improve processes and eliminate the possibility of errors or defects.

Six Sigma professionals are typically trained in a variety of statistical methods and tools and work in organizations to carry out improvement projects, optimize processes, and achieve measurable results in terms of cost reduction, quality improvement, and customer satisfaction.

Six Sigma follows a structured approach called DMAIC, which stands for Define, Measure, Analyze, Improve, and Control. Each step plays an important role in the overall process improvement effort. A brief description of each step follows:

  • Define
  • Measure
  • Analyze
  • Improve
  • Control
Define:

In this first step, the project team defines the problem or improvement opportunity. The team clarifies the project’s goals, scope, stakeholders, and outcomes. It is important to develop a clear understanding of what needs to be improved and why it is important.

In the critical first phase of project initiation, the project team begins the journey to carefully define the underlying problem or exploit opportunities for improvement. This requires in-depth research to formulate project goals, define scope, identify key stakeholders involved, and outline expected outcomes.

To illustrate, let’s consider the scenario of a software development project that aims to improve the user experience of a popular mobile application. The project team begins by identifying specific weaknesses or areas for improvement within the current application interface. This could be an issue with navigation efficiency, loading speed, or user engagement metrics. By carefully defining these aspects, the team sets clear goals to: B. Reduce user churn, increase time spent in app, and ultimately improve overall customer satisfaction.

Additionally, it is essential at this stage that the team develops a broad understanding of why solving these problems is so important. For example, you can analyze user feedback, conduct market research, and compare competitor products to understand the importance of improving the user experience of your application. This understanding not only serves as a guide throughout the project, but also ensures that subsequent steps are closely aligned with the overall goals and objectives initially set.

 

Measure:

Once the problem is defined, the team collects data related to the process being studied. Quantitative data is collected to understand the current state of the process and establish key performance indicators. The accuracy and precision of the measurement system are evaluated to ensure reliable data collection.

After clearly defining the problem at hand, the team begins a comprehensive data collection phase focused on the process at hand. This involves collecting quantitative data to gain insight into the current state of the process and set benchmarks for key performance indicators. An important aspect of this step is to ensure the reliability of data collection by assessing the accuracy and precision of the measurement system.

For example, imagine a manufacturing company that wants to optimize its production line to meet increasing demand while maintaining quality standards. Once various manufacturing performance issues are identified, the team begins collecting data on various aspects of the manufacturing process. This includes quantitative information such as production rate, downtime, error rate, and asset utilization.

For example, teams can use sensors and monitoring devices installed on machines to collect real-time data on production rates and downtime. Additionally, manual observations and measurements can be performed to evaluate factors such as product quality and resource consumption.

At the same time, the team evaluates the measurement system used to collect this data. We ensure sensors are properly calibrated and calibrated regularly to maintain accuracy. Likewise, manual measurement equipment is calibrated and standardized to minimize data collection errors.

Studies can also be conducted to assess the reliability of data collected with these measurement systems. For example, you can compare data collected from different sensors or measurement devices to ensure consistency and reliability.

Overall, this thoughtful approach to data collection and measurement system evaluation ensures your team has a solid foundation of reliable data from which to analyze and make informed decisions about process improvement initiatives.

 

Analyze

At this stage, the team analyzes data to identify root causes of process errors or deviations.
Statistical tools and techniques are used to analyze data trends, patterns, and relationships. The goal is to better understand why processes are not reaching desired performance levels and to prioritize areas for improvement.

At this stage, the team conducts a comprehensive examination of the data to identify root causes of any defects or deviations in the process. Using a variety of statistical tools and techniques, the team examines data trends, patterns, and relationships to gain valuable insights. This analysis process is similar to solving a complex puzzle in which a team analyzes data to find why a process is not achieving the desired level of performance.

For example, consider a manufacturing situation where a company is experiencing a higher than acceptable rate of product defects. The analysis phase examines production data, uses statistical methods to identify correlations, and investigates potential factors contributing to errors. This may include variables such as machine settings, raw material quality, or operator performance. By carefully analyzing the data, the team gained a deeper understanding of the complex dynamics occurring in the manufacturing process.

The ultimate goal of this analysis effort is to identify current deficiencies as well as prioritize areas for improvement. By identifying root causes, teams can develop targeted strategies to improve overall process efficiency and performance. This lays the foundation for meaningful, sustainable improvement and ensures that your organization consistently meets or exceeds its performance goals.

 

Improve

Based on the results of the analysis phase, the team develops and implements solutions to address the identified root causes. A variety of improvement techniques and tools are used to optimize processes and eliminate errors. Pilot testing can be conducted to verify the effectiveness of the proposed solution prior to full implementation.

After an extensive analysis phase, the team strategically formulates and implements solutions to identify root causes. This complex process requires the use of a variety of carefully selected improvement techniques and tools to optimize the overall workflow and eliminate system errors. Imagine a manufacturing plant that receives in-depth analysis of the inefficiencies in its production line to find parallels with real-world situations. Based on the information gained from this analysis, the team introduces and tests various techniques, such as lean manufacturing principles or Six Sigma methods, to improve manufacturing processes and solve identified problems. Additionally, before beginning full implementation, teams can conduct pilot testing to carefully test the effectiveness of proposed solutions and ensure that improved processes actually lead to desired improvements and outcomes. This thoughtful, iterative approach not only prevents potential disruptions, but also promotes a culture of continuous improvement within the organizational structure.

 

Control

The final step is to establish controls to sustain improvement. Control and monitoring systems are in place to ensure that processes remain stable and performance objectives are consistently achieved. Standard operating procedures, training programs, and ongoing data collection are implemented to support continuous improvement efforts.
The final stage of the improvement process involves implementing strong controls to maintain and sustain the improvements achieved. This requires the establishment of comprehensive control and monitoring systems to ensure sustainable stability of the process and consistent alignment with performance targets. Several strategies are taken to facilitate this, including formalizing and adhering to standard operating procedures, introducing structured training programs, and collecting relevant data on an ongoing basis. Together, these elements form a dynamic framework that not only ensures improvements but also promotes a supportive environment for continuous improvement.

For example, consider a manufacturing company that has successfully optimized its production process to increase efficiency and reduce defects. As a final step, the company implements a strict control system, including standardized operating procedures for each production step. At the same time, employees receive regular training to keep up to date on optimized processes and best practices. In addition, a sophisticated monitoring system is incorporated that continuously collects and analyzes production data to detect deviations from established standards. This comprehensive approach ensures reliable production processes, achieves performance goals, and lays the foundation for continuous improvement in productivity and product quality.

Throughout the DMAIC process, Six Sigma teams use a combination of problem-solving methods, statistical analysis, and quality management tools to drive systematic improvement and achieve measurable results. The ultimate goal is to provide a product or service that consistently meets customer needs and minimizes errors and variability in the process.

In the DMAIC (Define, Measure, Analyze, Improve, Control) process, Six Sigma teams take a comprehensive approach that integrates a variety of problem-solving methods, statistical analysis, and quality control tools. This multifaceted strategy contributes significantly to achieving systematic improvement and tangible results. The overall goal is to ensure consistent delivery of products or services that meet customer requirements and minimize errors and variability in the process.

For example, imagine a manufacturing scenario where a Six Sigma team is tasked with improving the production of specific electronic components. During the definition phase, the team clearly describes the problem and identifies potentially high defect rates in the current manufacturing process. The measurement phase uses statistical analysis to quantify the problem and establish baseline metrics.

In the next “analysis” phase, the team investigates deeper into the cause of the error. Use statistical tools such as Pareto charts or fishbone diagrams to identify important factors contributing to deviations and errors. Armed with this knowledge, the team moves to the “advanced” stage and implements targeted changes in the production process. This may include adjusting machine settings, improving quality control protocols, or introducing new technology.

To ensure the continued success of the improvement, the team moves into the “Control” phase. Quality management tools, such as control charts and process maps, are used to monitor and maintain improved processes over time. This iterative approach within the DMAIC framework allows for a continuous cycle of improvement that minimizes defects and increases consistency in the final product that meets or exceeds customer expectations.

Simply put, Six Sigma teams strategically use the DMAIC process to leverage a variety of problem-solving methods, statistical analysis, and quality control tools. This holistic approach not only solves immediate problems, but also creates a framework for continuous improvement, ultimately achieving the goal of delivering a high-quality product or service that consistently meets the needs of our customers.

 

How to implement Six Sigma in the pharmaceutical industry?

Implementing Six Sigma in the pharmaceutical industry requires a systematic approach to improve processes, reduce errors, and increase overall efficiency. Six Sigma is a data-driven methodology that aims to achieve near-perfect performance by reducing variation and eliminating defects. Here are the steps to implement Six Sigma in the pharmaceutical industry:

  • Commitment to leadership
  • Training and education
  • Identify critical processes
  • Define key indicators (Y) and process indicators (X)
  • DMAIC Methodology
  • Cross-functional team
  • Use of statistical tools
  • Documentation and standardization
  • Risk Management
  • Culture of continuous improvement
  • Compliance and regulatory considerations
  • Measurement and evaluation
Commitment to leadership:

Maintain top management’s commitment to support and promote Six Sigma initiatives. Leadership involvement is critical to success.

To ensure the success and effectiveness of these efforts, it is important to ensure an ongoing commitment from senior management to actively support and advance Six Sigma initiatives. Leadership engagement plays a critical role in aligning an organization to a culture of continuous improvement and operational excellence.

In fact, let’s imagine a manufacturing company that wants to improve its production process through Six Sigma methodology. Top management commitment is similar to the CEO publicly supporting and prioritizing Six Sigma initiatives, demonstrating a strong commitment to their implementation. This commitment can manifest itself in a variety of ways, including allocating resources, providing necessary training, and integrating Six Sigma principles into the company’s strategic vision.

Additionally, leadership involvement is more than just support. This includes being an active participant in the Six Sigma journey. For example, business leaders can lead by example by participating in improvement projects or working regularly with Six Sigma teams to understand problems and provide guidance. This hands-on approach not only motivates employees, but also demonstrates leadership’s true commitment to the initiative.

By ensuring top management commitment and active leadership involvement, companies can create an environment conducive to Six Sigma success. This commitment extends throughout the organizational hierarchy and promotes a culture of accountability, continuous improvement, and ultimately achieving real and sustainable operational excellence.

 

Training and education:

Ensure that employees at all levels receive appropriate training in Six Sigma methodology. This includes training employees at different levels: yellow belt, green belt, black belt, etc.
It is important to ensure comprehensive training in Six Sigma methodology for employees at all levels within the organization. This includes offering Yellow Belt, Green Belt and Black Belt training programs tailored to the diverse needs and skill levels of our employees.

More specifically, investing in employee training at all levels of the organization will ensure that Six Sigma principles are understood and applied consistently. For example, introducing “yellow belt” training for young professionals can provide them with the basic knowledge to actively contribute to improvement plans. These employees can identify and solve underlying problems, fostering a culture of bottom-up continuous improvement.

Green Belt training moves up the hierarchy and deepens the understanding of Six Sigma tools and methods for mid-level employees. This will help drive participation in project management and data-driven decision-making, as well as drive process improvement initiatives within the department.

At the highest levels of an organization, black belt training is important for senior executives and key decision makers. This training provides you with the skills to execute large-scale process improvement projects and align your business goals with Six Sigma principles for maximum impact. For example, a manufacturing company can significantly improve production efficiency and product quality by implementing a black belt initiative.

In essence, a structured and step-by-step Six Sigma training program ensures that employees at all levels are not only proficient in the methodology but also contribute significantly to the company’s overall efficiency, quality and strategic goals. This approach fosters a culture of continuous improvement across the entire organization, driving sustainable success and competitive advantage in a dynamic business environment.

 

Identify critical processes:

Identify and prioritize critical processes that have a significant impact on quality, efficiency, and customer satisfaction. This may include manufacturing processes, quality control, and supply chain processes.
Identify and prioritize critical processes that have a significant impact on overall quality, efficiency, and customer satisfaction. These critical processes include a variety of activities such as manufacturing processes, quality control procedures, and supply chain management protocols. These factors collectively determine a company’s success and reputation, so it’s important to evaluate and prioritize them carefully.

For example, in a manufacturing process, a company must identify the critical steps that contribute to the quality and performance of the final product. This includes testing at every stage, from raw material procurement to final assembly, to ensure stringent quality standards are met at every step.

Quality management systems play an important role in maintaining and improving the overall quality of your products. By closely inspecting and testing products at various stages of production, companies can detect defects or deviations from desired specifications, thereby preventing substandard products from reaching the market. This not only ensures brand reputation but also increases customer trust and satisfaction.

Additionally, optimizing supply chain processes is important to ensure timely and cost-effective product delivery. A real-world example of this is a global e-commerce giant that strategically manages its supply chain to speed delivery times, reduce costs, and improve the overall customer experience. By increasing the priority of critical aspects such as inventory management, transportation logistics, and supplier relationships, companies can efficiently meet customer expectations.

Identifying and prioritizing inherently critical processes is not simply a theoretical exercise, but a practical approach that has a direct impact on the success and sustainability of an organization. Practical examples demonstrate the importance of these processes in various sectors.

 

Define key indicators (Y) and process indicators (X)

Clearly define key performance indicators (Y) aligned with company goals. Identify process indicators (X) that can impact the results and performance of critical processes.

Clearly formulate and outline key performance (Y) indicators that align with the organization’s overall goals. Identify process metrics (X) that impact the outcomes and efficiency of critical operational processes through comprehensive analysis. This requires careful study of the interactions between various organizational parameters and goals to improve strategic direction.

For example, imagine a manufacturing company that strives to improve product quality and customer satisfaction as its primary business goals. In this context, a key performance indicator (Y) might be the percentage of defect-free products delivered to customers. To identify relevant process indicators (X), companies can scrutinize their manufacturing processes, considering factors such as raw material quality, machine availability, and employee training as their potential impact on product quality. This deeper analysis allows organizations to directly link selected metrics to broader goals and promotes a more targeted and effective approach to measuring and improving performance.

 

DMAIC Methodology:

Drive your development projects forward using the Define, Measure, Analyze, Improve, Control (DMAIC) methodology at the heart of Six Sigma. Definition: Clearly describe the problem, project scope, goals, and customer requirements. Measure: Collect and analyze data to measure current process performance. Analysis: Identify the root causes of deviations and errors in your processes. Improvement: Develop and implement solutions to address root causes and improve processes. Control: Establish control systems to maintain improvements over time.

The use of the DMAIC methodology, a fundamental Six Sigma framework, has proven to be an invaluable guide to successfully managing improvement initiatives. This approach includes five key steps: define, measure, analyze, improve, and control, each of which plays a key role in streamlining and improving the process. Real-life examples illustrate the importance and practical application of each step.

  • Define
  • Measure
  • Analyze
  • Improve
  • Control
Define

At this early stage, it is important to carefully outline the parameters of the project. Imagine a manufacturing company struggling with poor product quality. The definition phase allows the company to properly formulate the problem, define the project scope, set clear goals, and capture the customer’s requirements. This may include identifying specific product defects, understanding customer expectations, and scoping the manufacturing process for testing.

Measure

Once the problem is accurately defined, the next step is to quantify the current state. In the manufacturing example, companies can collect and analyze data on defect rates, production times, and other relevant metrics. These careful measurements provide organizations with a quantitative understanding of process performance and provide a solid foundation for subsequent analysis.

 

Analyze

Based on the available information, the analysis phase begins to find the root causes of process deviations and errors. Continuing with the manufacturing scenario, this may include detailed statistical analysis to identify patterns, correlations, and outliers that impact product quality. Identifying these root causes is critical to developing effective solutions in the next steps.

 

Improve

Armed with the information gained through analysis, the advanced phase focuses on developing and implementing solutions to address the identified root causes. For manufacturing, this may mean introducing new machinery, improving production protocols, or improving employee training to eliminate or mitigate sources of error. The goal is to optimize processes and achieve measurable improvements.

 

Control

The final step, control, is about maintaining the improvements achieved through the improvement plan. On the manufacturing side, this may include establishing control systems such as continuous monitoring of key performance indicators, implementing standard operating procedures, and providing regular training to ensure improvements are sustained over time. This step acts as a safeguard against regression and ensures the continued success of the optimized process.

By exploring the DMAIC methodology, businesses can create a culture of continuous improvement by regularly solving problems, increasing efficiency, and delivering value to customers.

 

Cross-functional team:

Build cross-functional teams with members from various departments to ensure a holistic approach to problem solving.

Building cross-functional teams that involve people from different departments is essential to encourage a holistic and comprehensive approach to problem solving. By bringing together teams with diverse skills and perspectives, companies can gain a wealth of knowledge and experience that leads to more innovative and effective problem solving.

Basically, imagine a scenario where a company is solving a complex business problem, such as improving customer satisfaction. Rather than relying solely on insights from your customer service department, it’s important to build a cross-functional team that includes customer service, marketing, product development, and finance. Your customer service team can provide insight into common customer issues, your marketing team can provide data on customer preferences, your product development team can provide ideas for product improvements, and your finance team can provide suggestions. Evaluate the commercial viability of your solution.

This collaborative approach allows organizations to approach problems from multiple angles to achieve more comprehensive and strategic solutions. Additionally, cross-functional teams encourage effective communication, break down silos between departments, and foster a culture of collaboration, ultimately increasing the overall efficiency and effectiveness of the problem-solving process.

 

Use of statistical tools:

Use statistical tools and techniques to analyze data and make informed decisions. Common tools include process mapping, control charts, regression analysis, and experimental design.
Use statistical methods and tools to comprehensively analyze data and make informed decisions. A variety of statistical techniques, including process mapping, control charts, regression analysis, and experimental design, facilitate in-depth investigation and understanding of complex data sets. These tools have become essential tools in a variety of fields, helping professionals gain meaningful insights, identify patterns, and make data-driven decisions that contribute to business success.

For example, in manufacturing, process mapping allows detailed visualization of each production step to identify potential bottlenecks and optimize workflow. Control charts help you monitor and maintain the stability of your production process, ensuring consistency and quality. Regression analysis can be used in marketing to develop targeted strategies by evaluating the impact of various variables on sales performance. Additionally, experimental designs have proven valuable in research and development settings because they allow scientists to systematically examine various factors and interactions to optimize results.

By incorporating these statistical tools into their decision-making processes, professionals in a variety of fields can improve their ability to draw meaningful conclusions from data, enabling them to make more effective and strategic decisions in their fields.

 

Documentation and standardization:

Document processes and standardize best practices to ensure consistency and repeatability.
Systematic documentation of processes and standardization of best practices are key steps in ensuring uniformity and reproducibility of positive results. By carefully documenting each step of the process and creating a standardized set of best practices, companies can streamline operations, increase efficiency, and reduce errors. This approach not only promotes a consistent and structured work environment, but also allows for continuous improvement.

In a real-world scenario, imagine a manufacturing company trying to improve its production line. By documenting each step of the manufacturing process using specific instructions, parameters, and quality management systems, organizations can ensure that each product meets desired standards. In this context, standardizing best practices may include identifying the most efficient and effective methods for assembly, quality assurance, and packaging. Not only does this ensure consistency in the final product, but it also makes it easier to hire new employees following established guidelines.

Similarly, in service-centric industries such as customer support, standardizing documentation processes and best practices can help deliver a more consistent and reliable customer experience. By defining steps to manage customer requests, resolve issues, and maintain high service standards, the organization ensures that all customer interactions meet established standards. This approach not only increases customer satisfaction, but also allows companies to identify opportunities for improvement and systematically implement change.

In essence, standardizing documented processes and best practices is a strategic investment that pays off in terms of operational efficiency, quality assurance, and adaptability to changing circumstances. It provides a foundation for continuous improvement, provides clear guidance to employees, and ultimately contributes to the overall success and sustainability of the organization.

 

Risk Management:

Integrate risk management principles into Six Sigma projects to anticipate and mitigate potential problems.
Incorporating risk management principles into Six Sigma projects is important to proactively identify and resolve potential problems. By seamlessly integrating risk management practices, companies can increase the overall effectiveness and success of their Six Sigma initiatives. This strategic approach includes a comprehensive assessment of potential risks throughout the project life cycle to take timely corrective action and ensure smooth project delivery.

For example, imagine a manufacturing company that uses Six Sigma methods to improve its production process. Without risk management integration, projects can encounter unexpected problems such as supply chain disruptions, machinery failures, or changing regulatory requirements. By actively incorporating risk management principles, project teams can systematically evaluate these potential challenges, develop contingency plans, and take preventive actions to minimize their impact on project plans and outcomes.

Therefore, incorporating risk management not only aligns with Six Sigma process improvement goals, but also adds a level of resilience to the project, allowing it to better adapt to external variables. This comprehensive approach contributes to the long-term success of the organization by encouraging a culture of continuous improvement and risk-based decision-making within Six Sigma.

 

Culture of continuous improvement:

Promote a culture of continuous improvement that encourages employees to continually identify and solve problems.
By fostering a work environment focused on continuous improvement, we not only empower our employees but also actively motivate them to continuously identify and solve problems. This involves developing a mindset to continually improve and improve various aspects of work processes, productivity, and overall organizational effectiveness.

In this dynamic culture of continuous improvement, employees make a critical contribution to improving operational processes and identifying bottlenecks. By instilling a sense of ownership and responsibility, people are not only encouraged, but they feel a real sense of responsibility for evaluating solutions, proposing solutions, and implementing improvements to streamline workflows and increase the quality of results.

A clear example of this approach is the automotive industry. Leading automobile manufacturers promote a culture of continuous improvement in their pursuit of excellence. Assembly line workers are encouraged to identify inefficiencies or potential improvements in the production process. This can range from advice on coordinating orders on the assembly line to innovative solutions to reduce waste. Through regular team meetings and feedback sessions, these organizations create an environment where all employees are not only actively engaged, but also a catalyst for continuous improvement, contributing to the company’s overall success and innovation.

By incorporating this philosophy into the company’s DNA, a culture of continuous improvement becomes more than just a buzzword. Be an engine of sustainable growth, innovation and adaptability. This approach allows employees to not only respond to immediate problems but also actively identify opportunities for improvement, creating a thriving work environment in a cycle of continuous development and excellence.

 

Compliance and regulatory considerations:

Ensure Six Sigma initiatives comply with industry regulations and standards. Compliance with regulatory requirements is very important in the pharmaceutical industry.
It is important to ensure that your Six Sigma initiatives are fully compliant with industry norms and standards. Compliance with regulatory requirements is especially critical in the dynamic environment of the pharmaceutical industry, where strict compliance is not only a best practice but a non-negotiable requirement.

In the pharmaceutical industry, aligning Six Sigma initiatives with industry regulations is like a compass guiding a ship in choppy waters. For example, regulatory authorities such as the US Food and Drug Administration (FDA) or the European Medicines Agency (EMA) establish guidelines and standards that must be carefully followed during drug development and manufacturing. Deviating from these regulations not only jeopardizes patient safety, but also jeopardizes the reputation and reputation of pharmaceutical companies.

Imagine a scenario where a pharmaceutical company implements Six Sigma methodology in its manufacturing process. Compliance with regulatory requirements requires systematically optimizing processes to meet quality standards while adhering to strict pharmaceutical manufacturing guidelines. This may include implementing statistical process controls to monitor critical parameters, conducting thorough risk assessments, and maintaining comprehensive documentation throughout the manufacturing life cycle.

Failure to align Six Sigma initiatives with pharmaceutical industry regulations can have serious consequences. Potential consequences include product recalls, legal consequences, and loss of company credibility. Therefore, fully understanding and integrating compliance into Six Sigma initiatives not only improves performance, but also protects the integrity of the entire pharmaceutical supply chain. Inherently linking Six Sigma and compliance is not just a procedural imperative, but a strategic imperative for the sustainable success of the pharmaceutical industry.

 

Measurement and evaluation:

We continuously measure and evaluate the success of Six Sigma projects using key performance indicators and stakeholder feedback.
We continuously measure and evaluate the effectiveness of our Six Sigma initiatives by applying a comprehensive approach, including carefully monitoring key performance indicators (KPIs) and obtaining valuable feedback from a variety of stakeholders. This continuous evaluation process serves as an important mechanism to ensure the continued success and improvement of Six Sigma projects.

From a practical perspective, let us consider a real-life example of a manufacturing company applying Six Sigma principles to improve its production processes. Companies can quantitatively measure the impact of their Six Sigma initiatives by setting KPIs such as defect rates, production cycle times, and customer satisfaction scores. Regularly collecting and analyzing data on these metrics allows companies to track improvements over time and identify areas requiring further optimization.

Additionally, involving stakeholders, including employees, customers, and management, in the feedback loop can provide valuable qualitative insights. For example, manufacturing employees can provide insight into the real-world challenges and successes of implementing Six Sigma methods, and customer feedback can provide insight into how improvements translate into improved product quality and satisfaction.

Basic principle of Six Sigma?

By combining quantitative metrics and qualitative feedback, organizations gain a holistic view of Six Sigma project success. This iterative process of measurement and evaluation forms the basis for continuous improvement and allows the company to adjust its strategy, improve its processes and promote sustainable operational excellence.

Remember that successful implementation of Six Sigma requires a commitment to continuous improvement, ongoing commitment, and cultural change within the organization. Regular reviews and feedback loops are essential to sustain long-term improvements.

What is Six Sigma? Read More »

Data Integrity with 21 CFR

Meaning of Data Integrity

Data Integrity with 21 CFR, Data integrity, as defined in 21 Code of Federal Regulations (CFR), particularly in the context of pharmaceutical and related industries, refers to the completeness, consistency, and accuracy of data throughout its life cycle. Ensuring data integrity is critical to maintaining the quality, safety, and efficacy of medicines.

The U.S. Food and Drug Administration (FDA) emphasizes the importance of data integrity in a variety of regulations, including 21 CFR Part 11 (electronic records, electronic signatures) and 21 CFR Part 211 (Current Good Manufacturing Practices for Drug Products). These regulations establish requirements for the creation, modification, maintenance, retrieval and storage of documents and electronic signatures, as well as documentation practices for production processes.

The key principles related to data integrity according to 21 CFR are:

  • Attributable
  • Legible
  • Contemporaneous
  • Original
  • Accurate
  • Complete
  • Enduring
 
Attributable:

Data must belong to the person who performed the action or recorded the information, ensuring accountability and traceability of the data.

To maintain accountability and traceability throughout the process, it is important to assign data to those responsible for creating or recording it. By linking data to specific individuals, organizations can establish a clear chain of accountability, increase transparency, and promote effective decision-making. This approach not only promotes integrity, but also helps identify errors, resolve discrepancies, and comply with legal requirements.

Let’s consider a real medical scenario. When a nurse administers medication to a patient, this action should be attributed to the nurse who performed it. Healthcare facilities ensure accountability by recording the names of healthcare workers along with records of medication administration. If a problem such as an adverse reaction or medication error occurs, the nurse in charge can be immediately identified and corrective action can be taken quickly. Additionally, during regulatory audits or inspections, clear data attribution can help demonstrate that a facility complies with established protocols and standards.

Additionally, in industries such as finance or manufacturing, connecting data with the people involved in key transactions or processes is equally important. For example, a financial institution must be able to track the specific employee who initiated or approved each financial transaction. This mapping not only helps detect fraudulent activity, but also allows companies to analyze performance, identify training needs and optimize processes.

Connecting data to people provides the foundation for accountability and traceability across domains. Whether in healthcare, finance, manufacturing, or other fields, this practice improves data integrity, promotes effective decision-making, and ensures regulatory compliance.

 
Legible:

Data should be clear and easy to read. Permanent records must be made to prevent changes, and any changes must be documented with appropriate approval.

It is essential to ensure transparency and readability as well as integrity and security of data by permanently recording and properly documenting changes with approved approvals. This means that data must be presented in a way that is easy to understand and access, as well as stored securely to prevent unauthorized alteration.

Imagine a real-life scenario in a financial institution where customer transaction records are kept. Each transaction must be recorded clearly and accurately so that authorized personnel can understand all relevant details. For example, when a customer makes a deposit or withdrawal, the transaction details, including amount, date, and account information, must be clearly and accurately recorded.

Additionally, any changes or updates to the data must be carefully documented to maintain the integrity of these records. For example, if a customer objects to a transaction and requests a correction, the change in the transaction record must be clearly stated, the reason for the change, and whether or not a specific person, such as a manager or supervisor, has authorized it. This document not only ensures transparency but also serves as an audit trail for accountability.

By adhering to the principles of transparency, readability, integrity, and documentation, organizations can maintain the trustworthiness and trustworthiness of their data, ultimately increasing stakeholder trust and promoting informed decision-making.

 
Contemporaneous:

Data should be recorded at the time of observation or action and not entered retroactively. This helps ensure accuracy and reliability.

To maintain accuracy and reliability, it is important to collect data concurrently with observations or actions rather than entering them after the facts have been confirmed. This approach ensures that data reflect the actual circumstances in which they occur and minimizes the risk of errors, omissions, or distortions that may arise due to memory errors or subjective interpretations.

For example, imagine a medical situation where a nurse is administering medication to a patient. Recording the dose, time of administration, and reactions observed immediately after the event ensures the accuracy of the medical record. Entering this information later increases the likelihood of errors due to the passage of time, the need for multitasking, and confusion with other patient information. This can have serious consequences, including incorrect treatment planning and reduced patient safety.

Even during the manufacturing process, real-time data recording during the production process allows deviations or errors to be quickly detected and corrected. Once information is collected, discrepancies may go unnoticed and lead to poor product quality, production delays, or safety hazards. Timely data collection serves as the basis for informed decision-making, process optimization and quality assurance in a variety of fields and prevents loss of subsequent data entry.

 
Original:

Data must be original or a faithful copy, and any copy made must preserve the content and meaning of the original data.
Data integrity requires that data remain reliable and unchanged throughout its lifecycle. This means that the data must be the original or master copy, and any duplicates must maintain the accuracy and validity of the original dataset.

For example, in the context of scientific research, maintaining data integrity is important to ensure the reliability of research results. Consider a scenario where a team of researchers is conducting an experiment to test the effectiveness of a new drug. Data collected during testing, including patient responses, doses, and observations, must be original and accurately recorded. If your research team needs to share this data with other scientists or regulatory agencies, you can make copies for distribution. However, such copies must reproduce the original dataset without modifications or omissions. Deviations from the original data can lead to misinformation or interpretation of test results, potentially affecting the validity of the study and influencing future treatment decisions.

Likewise, maintaining the integrity of financial information in a business environment is critical to decision-making and regulatory compliance. Let’s say a company prepares financial reports based on transactions recorded in its accounting system. These reports are used as a basis for evaluating company performance and making strategic decisions. Copies or extracts of this financial information, including reports or regulatory documents distributed to stakeholders, must accurately reflect the information contained in the original documents. Failure to maintain the integrity of financial information can result in reporting errors that can mislead investors, regulators and other stakeholders and result in loss of financial influence and trust.

Whether in scientific research, business operations, or other fields, maintaining the integrity of information by ensuring its originality or maintaining reliable copies is important to maintain its reliability, reliability, and usefulness.

 
Accurate:

Data must be accurate, consistent, and reliable. Any errors or discrepancies must be immediately identified, investigated and documented.
Ensuring data integrity is critical and requires accuracy, consistency, and reliability at all times. Imagine a situation where financial institutions rely on data to make important investment decisions. Correct information ensures the robustness and profitability of your investments. Data consistency ensures that trends and patterns can be reliably identified and managed, while reliability builds trust between stakeholders and investors. However, even in systems that are managed with the utmost care, errors and inconsistencies can occur. For example, inconsistencies in financial information can lead to poor investment decisions that can result in significant losses. Therefore, it is important to immediately detect, investigate, and document these errors or anomalies to quickly resolve them and prevent further negative impacts.

This rigorous approach not only protects data integrity, but also strengthens trust in the decision-making process and ultimately contributes to the success of the company.

 
Complete:

Data must be complete and contain all relevant information necessary to understand its context and meaning.
It is important to ensure that the data is complete and includes all relevant information needed to understand its context and meaning. In practice, this means that each dataset should contain not only the underlying data, but also additional details that provide a broader understanding of the content.

Consider a sales report from a retail company. A comprehensive dataset not only lists total sales data, but also includes additional relevant information such as the time period, region, specific products sold, pricing details, customer demographics, marketing campaigns conducted during the time period, and external information. These are factors that affect sales, such as economic trends or seasonal fluctuations. By incorporating this additional data, stakeholders can understand the broader context surrounding sales statistics and support accurate analysis, decision-making, and strategic planning.

Moreover, integrity extends beyond purely quantitative aspects to qualitative aspects. For example, comprehensive data from a physician’s office includes not only numerical measurements but also qualitative descriptions such as patient demographics, medical history, lifestyle factors, and treatment protocols. This holistic approach allows researchers to thoroughly analyze data and make reliable decisions by considering all relevant factors that may affect results. Data integrity allows users to gain meaningful insights, make informed decisions, and take appropriate actions with a full understanding of the underlying information.

 
Enduring:

Data must be stored for as long as legally required and protected from loss, damage, or unauthorized access during storage and retrieval.
To maintain integrity and compliance within your organization, it is important to ensure that data retention complies with regulatory requirements and protects data from loss, corruption, or unauthorized access throughout its lifecycle. Compliance regulations, such as GDPR in Europe or HIPAA in the United States, require specific retention periods for different types of data, from financial records to personal health information. Compliance with these requirements not only reduces legal risks, but also strengthens trust between customers and stakeholders.

For example, consider a healthcare organization responsible for managing patient medical records. HIPAA regulations require that patient health information (PHI) be retained for at least six years from the date it was last created or used. Failure to comply may result in serious penalties, including fines and legal penalties. Therefore, healthcare providers must implement strict data retention policies and use secure storage solutions to ensure that protected health information remains accessible for as long as needed and is protected from breach or data loss.

Data Integrity and Why Is It So Important?

Data protection also goes beyond legal compliance and includes protecting confidential information that could harm individuals or jeopardize business operations. In the age of digital transformation, data breaches are becoming increasingly common and can have far-reaching consequences, including financial loss and reputational damage. Implementing encryption protocols, access control, and regular data backup are essential strategies for strengthening your data security system.

Organizations must take a proactive approach to data management, balancing regulatory obligations with data integrity and privacy needs. This not only helps mitigate legal risks, but also fosters a culture of trust and accountability among stakeholders, ultimately increasing competitive advantage in an increasingly data-driven environment.

Adhering to these principles ensures that data generated, recorded and managed in the pharmaceutical manufacturing process is reliable, verifiable and meets legal requirements. Failure to adhere to data integrity principles may result in regulatory action, including warning letters, fines, and product recalls. Therefore, pharmaceutical companies must establish robust data management systems and procedures to ensure data integrity throughout their operations. This is all about the Data Integrity with 21 CFR.

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What are the leading pharmaceutical companies globally?

Leading pharmaceutical companies s as of the last update in January 2022, the world’s  are:

  • Johnson & Johnson (J&J)
  • Pfizer Inc.
  • Novartis AG
  • Roche Holding AG
  • Merck & Co., Inc. (MSD outside North America)
  • AbbVie Inc.
  • Sanofi
  • GlaxoSmithKline plc (GSK)

 

Johnson & Johnson (J&J):

J&J does not prefer a diversified portfolio that includes drugs, medical devices, and consumer health products. It is well known for its pharmaceutical products such as Remicade, Stelara, and Xarelto, as well as consumer brands such as Band Aid and Tylenol.
Johnson & Johnson (J&J) is widely known for its diverse products, including pharmaceuticals, medical devices, and consumer health products. This diverse portfolio not only highlights the company’s resilience, but also promises to address different aspects of healthcare challenges.

In the pharmaceutical sector, J&J has an impressive portfolio of drugs that have had a significant impact on global health outcomes. For example, consider Remicade, an innovative biologic drug used to treat autoimmune diseases such as rheumatoid arthritis and Crohn’s disease. Its impact has transformed the lives of millions of patients, alleviating debilitating symptoms and improving quality of life.

Stellara also represents another significant achievement in J&J’s pharmaceutical space. These innovative biological drugs have revolutionized the treatment of diseases such as psoriasis and psoriatic arthritis, providing patients with new experiences and effective long-term treatment options.

J&J has left an indelible mark on consumer engagement with iconic brands such as Band-Aid and Tylenol. These renowned brands have become synonymous with trust and reliability, providing consumers with essential medical solutions for everyday illnesses and injuries. For example, Band-Aid’s innovative band-aids have been in first aid kits for generations, providing a quick and convenient solution for treating minor cuts and scrapes. Likewise, Tylenol is the anti-inflammatory drug of choice for millions of people and is effective in relieving headaches, muscle pain, and fever.

Through its diverse portfolio, Johnson & Johnson implements a holistic approach to healthcare, meeting the needs of patients and consumers at every stage of their healthcare journey. J&J continues to make a significant impact on health and well-being around the world, whether through breakthrough pharmaceutical advancements or trusted brands in consumer health.

 

Pfizer Inc.:

Pfizer is known for conducting groundbreaking research in vaccines, including the COVID-19 vaccine developed in collaboration with BioNTech. It also produces widely used medicines such as Lipitor, Viagra, and Lyrica.
Pfizer is acclaimed globally for its groundbreaking advancements in vaccine development, particularly its tremendous achievements in developing the COVID-19 vaccine in collaboration with BioNTech. Additionally, Pfizer’s influence extends beyond vaccines through its broad portfolio of widely used medicines, including Lipitor for cholesterol control, Viagra for erectile dysfunction, and Lyrica for neuropathic pain. This broad range of medicines highlights Pfizer’s commitment to meeting a variety of healthcare needs and improving the quality of life for millions of people around the world.

For example, consider Pfizer’s cholesterol-lowering drug Lipitor. It has played a key role in reducing the risk of heart disease and stroke for millions of patients around the world. By effectively controlling cholesterol levels, Lipitor helped people live healthier lives and highlighted Pfizer’s commitment to cardiovascular health. Likewise, Pfizer’s erectile dysfunction drug Viagra has revolutionized treatment options for this condition, providing a solution that significantly improves the quality of life for countless people and their partners. These real-life examples demonstrate the tremendous impact Pfizer’s innovative medicines can have on healthcare.

 

Roche Holding AG:

Roche is a Swiss multinational company known for its innovative oncology treatments such as Herceptin and Avastin. The company also has a strong presence in the diagnostics sector with products such as the Cobas series.

Roche, a renowned Swiss multinational, has shaped its identity through proven oncology innovation through innovative treatments such as Herceptin and Avastin. This drug has revolutionized cancer treatment, giving hope and extending the lives of countless patients around the world. In addition to therapeutics, Roche has also established a significant presence in diagnostics, particularly through its well-known Cobas series. These diagnostic tools allow healthcare providers to quickly and accurately diagnose diseases, make treatment decisions, and improve patient outcomes. For example, imagine a scenario where a patient presents with symptoms suggestive of breast cancer. Roche’s diagnostic solutions enable physicians to quickly determine the presence of specific biomarkers indicative of disease and develop targeted treatment plans tailored to a patient’s individual needs. Roche’s diverse contributions to treatment and diagnostics therefore play an important role in shaping the modern healthcare landscape and providing concrete solutions that have a positive impact on lives.

 

Novartis AG:

Novartis is known for a variety of drugs, including blockbusters such as multiple sclerosis treatment Gilenia and psoriasis treatment Cosentyx. The company also has a strong portfolio in ophthalmology and generic pharmaceuticals through its subsidiary Sandoz.

Novartis stands out in the pharmaceutical industry by offering a variety of drugs for a variety of medical needs. Notable successes include innovative drugs such as Gilenia, a leading treatment for multiple sclerosis, and Cosentyx, a powerful treatment for psoriasis. These drugs have significantly improved the quality of life and eliminated debilitating diseases for countless patients around the world.

Novartis also maintains a strong presence in ophthalmology and demonstrates its commitment to solving a variety of health problems by ensuring access to cutting-edge treatments for eye diseases. In addition, through our subsidiary Sandoz, we provide a variety of generic drugs at reasonable prices, contributing to improved accessibility to medical care by improving convenience and accessibility for patients around the world.

For example, consider a patient diagnosed with psoriasis, a chronic skin disease that severely impacts quality of life. Thanks to Novartis’ innovative drug Cosentyx, this patient now has significant relief from his psoriasis symptoms and can live a more comfortable and fulfilling life. Likewise, patients with multiple sclerosis can benefit from Gilenia by experiencing better symptom control and potentially slowing the progression of the disease, thanks to Novartis’ commitment to breakthrough pharmaceutical solutions.

 

Merck & Co., Inc. (MSD outside North America):

Merck is known for its contributions to medicine, including the first measles vaccine and the discovery of statins such as Lipitor. Key products include Keytruda for cancer and Gardasil for HPV.

Merck has an outstanding reputation in the field of medicine, particularly through groundbreaking advances that have had a significant impact on healthcare around the world. A notable achievement was the development of the first measles vaccine, making a significant contribution to saving countless lives around the world by stopping the spread of this highly contagious disease. Additionally, Merck’s statin discoveries, including drugs such as Lipitor, have revolutionized the treatment of cardiovascular disease, providing patients with effective solutions to control cholesterol levels and reduce heart disease risk.

Additionally, Merck continues to drive innovation through its core products. Keytruda, a groundbreaking immunotherapy, has revolutionized cancer treatment by harnessing the body’s immune system to attack and fight cancer cells, bringing new hope to patients battling various types of cancer. Likewise, Merck’s Gardasil is considered a breakthrough vaccine against human papillomavirus (HPV), a leading cause of cervical cancer and other related diseases. Through the large-scale administration of Gardasil, Merck has played an important role in preventing HPV infection and reducing the incidence of related cancers, resulting in significant advancements in public health.

To illustrate, let’s consider Gardasil’s effects in real life. Since its launch, Gardasil has helped reduce HPV infection rates and contributed to a reduction in cervical cancer cases in many countries where vaccination programs have been implemented. These tangible achievements highlight Merck’s commitment to advancing medicine and improving health outcomes for people around the world.

 

AbbVie Inc.:

AbbVie rose to fame with its blockbuster drug Humira, one of the world’s best-selling autoimmune disease drugs. Drugs are also being developed for diseases such as cancer, hepatitis C, and Parkinson’s disease.
AbbVie is best known for its globally acclaimed pharmaceutical giant Humira, a treatment for autoimmune diseases. This outstanding performance not only strengthened AbbVie’s reputation but also placed the company at the forefront of pharmaceutical innovation. In addition to the groundbreaking success of Humira, AbbVie is committed to developing pioneering treatments across a variety of diseases. From cancer to hepatitis C to Parkinson’s disease, AbbVie’s relentless pursuit of therapeutic innovation is redefining medical possibility and providing hope and cures to the millions battling these devastating diseases.

For example, AbbVie’s development of a hepatitis C treatment has transformed the landscape of liver disease treatment. The drug they invented revolutionized the standard of care and gave patients more effective and tolerable options to fight this terrifying virus. Through careful research and development, AbbVie has not only improved outcomes for patients with hepatitis C, but also significantly reduced the burden of the disease on healthcare systems around the world.

Sanofi:

Sanofi is known for its broad portfolio that includes vaccines, rare diseases, diabetes, and cardiovascular diseases. Products such as Lantus for diabetes and Dupixent for eczema and asthma have contributed to its reputation.
Sanofi is widely recognized for providing a broad range of products across critical healthcare areas, including vaccines, rare diseases, diabetes, and cardiovascular disease. The company’s product portfolio includes innovative and important solutions such as Lantus, a leading drug for the treatment of diabetes, and Dupixent, which treats conditions such as eczema and asthma. These innovative treatments have not only strengthened Sanofi’s position in the pharmaceutical industry, but have also significantly improved patient outcomes globally.

To illustrate, consider the case of Lantus. This long-acting insulin has revolutionized diabetes management by providing patients with a reliable and effective way to control their blood sugar levels. With millions of people relying on Lantus to lead healthy lives, Sanofi’s commitment to developing cutting-edge treatments highlights Sanofi’s commitment to meeting the needs of the growing number of chronic disease patients.

Likewise, Dupixent’s effectiveness goes beyond existing treatments for asthma and eczema. By targeting the underlying mechanisms of these diseases, Dupixent offers a new approach to managing patients’ symptoms and improving their quality of life. Through ongoing research and development efforts, Sanofi demonstrates its commitment to innovation, ultimately improving health outcomes and solidifying its reputation as a leader in the pharmaceutical industry.

GlaxoSmithKline plc (GSK):

GSK is known for its vaccines, respiratory products, and consumer healthcare products. It manufactures vaccines such as Flurix and Boostrix, as well as medications such as Advair for asthma and Breo for COPD.
GSK stands out in the pharmaceutical industry with a prominent presence in vaccines, respiratory treatments and consumer health solutions. This renowned company has made significant contributions to public health through the development and distribution of important vaccines such as Flurix and Boostrix. These vaccines play an important role in preventing infectious diseases and protecting populations around the world.

Additionally, GSK’s commitment to respiratory health is demonstrated through innovative medicines such as Advair for asthma and Breo for chronic obstructive pulmonary disease (COPD). These treatments have transformed the lives of millions of people suffering from respiratory disease, providing relief and improving quality of life.

For example, consider a patient named Sarah who has suffered from asthma for many years. Despite taking a variety of medications, he continued to experience frequent illnesses and limitations in his daily activities. But after her doctor prescribed Advair, Sara noticed a significant improvement in her symptoms. He was able to breathe more easily, participate in physical activities without difficulty, and felt better overall.

Likewise, John, a COPD patient, had difficulty overcoming his condition. Constant coughing and difficulty breathing often leave you feeling tired and unable to do simple tasks. But after starting Breo treatment, John felt tremendous relief. He was able to breathe more easily, engage in activities he had previously avoided, and regain a sense of normalcy in his life.

These examples demonstrate how GSK products such as Advair and Breo are making a real impact on people’s lives by effectively treating respiratory diseases. This highlights the company’s commitment to meeting critical healthcare needs and improving public health outcomes.
These companies are known for their innovative research and development efforts, developing innovative drugs and treatments for a wide range of diseases. They also have a global reach and significant marketing capabilities, allowing them to distribute their products widely. Many of these companies also engage in philanthropy and partnerships to improve health outcomes around the world.

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Principle of PICS Guideline

Principle of PICS Guideline, The Cooperative Program on Pharmaceutical Inspection (PIC/S) provides guidance and standards for the manufacturing and distribution of pharmaceutical products. The basic principles of the PIC/S Directive can be summarized as follows:

  • Quality Assurance
  • Good Manufacturing Practices (GMP)
  • Risk-based approach
  • Compliance and Inspection
  • Documentation and Records
  • Continuous Improvement
  • Training and competency
Quality Assurance:

The PIC/S guidance emphasizes the importance of implementing a strong quality assurance system throughout the entire pharmaceutical manufacturing process. This includes strict control measures to ensure consistent quality of raw materials, intermediate products and finished products.

For example, compliance with stringent quality assurance measures in the production of common painkillers such as ibuprofen tablets ensures that raw materials, including active ingredients and excipients, meet predetermined standards of purity and potency. Additionally, strict controls are applied throughout the manufacturing process to ensure consistency and efficiency of the final product by monitoring factors such as temperature, humidity, and mixing time. By complying with the PIC/S guidelines, pharmaceutical manufacturers can increase confidence in the reliability and safety of their products, increasing trust among healthcare professionals and patients.

 

Good Manufacturing Practices (GMP):

PIC/S guidelines are based on internationally recognized GMP standards that establish minimum requirements for manufacturing, testing, storage, and distribution of pharmaceutical products. Adhering to GMP principles helps ensure that products are consistently manufactured and controlled according to quality standards.

In real-world situations, pharmaceutical companies diligently follow PIC/S guidelines and GMP standards to maintain product quality and safety. For example, pharmaceutical manufacturers carefully monitor manufacturing environments and ensure cleanliness and proper calibration of equipment to prevent contamination and maintain product purity. Likewise, a stringent quality control system is implemented throughout the manufacturing process to ensure the quality and capacity of each batch produced. By adhering to these standards, pharmaceutical companies protect public health and build trust among consumers. This highlights the important role of regulatory compliance in ensuring the integrity of medicines.

 

Risk-based approach:

PIC/S promotes a risk-based approach to pharmaceutical manufacturing and quality control. The goal is to identify potential risks to product quality and patient safety and implement appropriate measures to mitigate these risks. Risk assessment and management are an integral part of PIC/S guidance.

In real life, this approach manifests itself in a variety of ways in the pharmaceutical industry. For example, when manufacturing a drug, a company may perform a thorough risk assessment to identify potential sources of contamination, such as raw materials and manufacturing equipment, that could affect the quality or safety of the product. We then reduce these risks by implementing rigorous quality control systems and investing in technologies such as advanced filtering systems or automated monitoring.

Similarly, when developing a new drug, pharmaceutical companies carefully analyze the potential risks associated with the various stages of research, development, and clinical trials. This may include evaluating the safety profile of a new compound, identifying potential side effects, and anticipating regulatory hurdles. Strategic risk management can help companies address these issues more effectively to ensure that safe and effective medicines ultimately reach the market.

Overall, by emphasizing a risk-based approach, PIC/S promotes a culture of responsibility and care within the pharmaceutical industry, ultimately protecting both the well-being of patients and the integrity of medicines around the world.

 

Compliance and Inspection:

Compliance with PIC/S guidelines is important for pharmaceutical companies to ensure the quality, safety, and effectiveness of their products. Regulatory authorities conduct inspections to ensure compliance with PIC/S standards and regulations. These inspections evaluate the manufacturer’s facilities, processes, documentation and quality control systems.

The importance of PIC/S compliance in real-world situations can be clearly illustrated through examples where compliance improves product quality and leads to patient safety. For example, imagine a pharmaceutical company that carefully follows PIC/S guidelines when developing a major drug to treat a fatal disease. By adhering to these rigorous standards, manufacturers ensure that each batch of drug is produced consistently according to predetermined specifications, reducing the risk of contamination or dosing discrepancies. As a result, patients relying on these medications can have greater confidence in their safety and effectiveness, ultimately leading to better health outcomes.

Conversely, failure to comply with PIC/S guidelines can have serious consequences. For example, consider a pharmaceutical manufacturer that does not maintain proper documentation or implement appropriate quality control systems in its manufacturing process. These failures can lead to regulatory fines, product recalls, and most importantly, compromise patient safety. In extreme cases, non-compliance can result in substandard or adulterated medicines being distributed, posing a serious risk to public health.

PIC/S compliance serves as a cornerstone for pharmaceutical manufacturers, ensuring the supply of high-quality, safe and effective medicines to patients around the world while strengthening trust in the healthcare system.

Documentation and Records:

Proper documentation and records are an essential part of PIC/S guidelines. Manufacturers must maintain complete documentation of all aspects of drug manufacturing, including manufacturing processes, quality control testing, equipment maintenance, and dispensing records. Accurate and complete records are important to demonstrate compliance with legal requirements.

For example, in a pharmaceutical manufacturing plant, detailed documentation of the manufacturing process helps trace the path from raw materials to finished product. This includes accurately recording the dimensions, temperature and duration of each individual production step. Documenting quality control testing is important to ensure the integrity and efficacy of the final drug product and ensure it meets rigorous regulatory standards before reaching consumers.

Additionally, complete records of equipment maintenance schedules and procedures ensure that production machinery operates at optimal efficiency and product quality is maintained. These records allow you to immediately identify any discrepancies or discrepancies so that corrective action can be taken immediately to ensure compliance with production standards.

Distribution records also play a critical role in ensuring that pharmaceuticals are transported and stored under appropriate conditions, ensuring durability and efficiency throughout the supply chain. Documenting shipping details, storage temperatures, and handling procedures is essential to maintaining product integrity and regulatory compliance. Careful documentation practices not only promote regulatory compliance, but also maintain the integrity, safety, and efficacy of medicines, ultimately protecting public health.

 

Continuous Improvement:

PIC/S guidelines encourage a culture of continuous improvement in pharmaceutical manufacturing facilities. Manufacturers are encouraged to regularly review and evaluate their processes, systems and procedures to identify areas for improvement and implement corrective actions where necessary. Continuous improvement helps improve product quality, efficiency, and compliance.

For example, imagine a pharmaceutical company that regularly evaluates its manufacturing processes. Through regular assessments, the company identifies bottlenecks in the production line that slow down overall production. By taking corrective action, such as reorganizing work processes or investing in newer machinery, companies can increase production efficiency and meet demand more effectively.

Imagine if a manufacturer regularly reviewed its quality control procedures. During the analysis, the company discovered recurring problems with certain test methods that produced inconsistent results. By addressing this issue in a timely manner through improved staff training or the use of advanced testing techniques, manufacturers can strengthen the reliability of their quality assurance processes to ensure consistently high product quality.

In both situations, the commitment to continuous improvement required by the PIC/S guidance not only improves product quality but also enhances operational efficiency and regulatory compliance, contributing to the continued success of drug manufacturing efforts.

 

Training and competency:

People involved in the production of pharmaceuticals must be appropriately trained and have the necessary skills to perform their jobs effectively. The training program should include GMP principles, quality management systems, regulatory requirements, and related skills. Ensuring employee competency is essential to maintaining product quality and compliance.

For example, imagine a pharmaceutical company whose employees receive extensive training in GMP principles. You will learn the importance of maintaining a clean environment, properly documenting manufacturing processes, and following strict sanitation protocols to prevent contamination. This type of training allows your staff to consistently produce high-quality pharmaceutical products and reduces the risk of errors or deviations that could lead to regulatory violations or reduce product effectiveness.

Additionally, in another scenario, let’s say a regulatory agency is inspecting a pharmaceutical manufacturing facility. They note that all employees have undergone rigorous training in the quality management system, which allows them to effectively implement monitoring and control procedures at all stages of production. As a result, the facility always meets legal standards and ensures the safety and effectiveness of the medicines produced there.

Overall, the guiding principles of the PIC/S guidelines focus on ensuring the quality, safety, and effectiveness of pharmaceutical products through a comprehensive quality management system, compliance with GMP standards, a risk-based approach, regulatory compliance, continuous improvement, and qualified personnel. This is all about the Principle of PICS Guideline.

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Importance of Powders and Granules in Pharmaceutical Sector

Importance of Powders and Granules in Pharmaceutical Sector, In fact, powders and granules play an important role in the pharmaceutical industry due to their diverse applications and importance in drug formulation and manufacturing. Here are some key points that highlight its importance:

  • Drug Formulations
  • Uniform Dosing
  • Ease of handling and processing
  • Customization and Flexibility
  • Stability and Shelf Life
  • Improved bioavailability
  • Taste masking and palatability
  • Versatility of delivery systems
  • Quality Control and Assurance
  • Cost-effectiveness
Drug Formulations:

Powders and granules are used as essential ingredients in manufacturing various pharmaceutical dosage forms such as tablets, capsules, reconstituted powders and granules for oral administration.

Powders and granules play an essential role in the development and formulation of a wide range of pharmaceutical dosage forms. These forms include tablets, capsules, powders for reconstitution, and granules for oral administration.

Tablet preparations are made with powders and granules as main ingredients and are converted into hard, easy-to-take tablets through processes such as tableting and gluing. These tablets are popular with patients because they offer accurate dosage and convenient administration features.

Capsules, another common dosage form, consist of powders or granules enclosed in a gelatin or vegetarian shell. This encapsulation ensures accurate dosing and facilitates swallowing, improving patient compliance with the medication.

Powders formulated for reconstitution provide a convenient alternative for drugs that require storage stability or precise dosing. When these powders are mixed with a suitable solvent such as water, they are converted into an administrable liquid dosage form. Examples of this include antibiotics and pediatric medicines, where precise dosing is critical to therapeutic efficacy.

Granules formulated for oral administration offer advantages such as improved taste masking, controlled release, and improved stability. These granules can be formulated as multiparticulate systems, allowing for tailored release profiles and improved bioavailability. For example, sustained-release analgesic formulations use granules to provide long-term pain relief by reducing the frequency of administration.

In fact, consider having a simple pain reliever like ibuprofen on hand. Manufacturers can use powders or granules to make tablets for immediate relief, extended-release capsules, powders for reconstitution in pediatric patients, and orally disintegrating tablets that are difficult to swallow. Each formulation optimizes drug delivery to meet specific patient needs, highlighting the essential role of powders and granules in pharmaceutical development.

 

Uniform Dosing:

These solid forms provide the ability to ensure uniform dosing and consistent administration of the drug, which is important for drug effectiveness and safety.

Solid forms of drugs offer several advantages in that they allow maintaining consistent dosages and ensuring consistent administration of the drug. This consistency is important for the effectiveness and safety of pharmaceutical treatments.

First, solid forms, such as tablets or capsules, are formulated with precise doses of the active ingredient. This precision ensures that each dose contains the intended amount of drug, reducing the risk of underdosing or overdosing. For example, analgesic 500 mg tablets provide 500 mg of the active ingredient with each dose, giving patients and caregivers precise control over their dosing schedule.

Additionally, the controlled release mechanism of solid dosage forms contributes to sustained administration of the drug over long periods of time. For example, extended-release tablets or capsules release the drug into the bloodstream in a slow, controlled manner while maintaining therapeutic concentrations in the body. These extended releases are particularly useful for drugs that require sustained action or have a narrow therapeutic window, where fluctuations in drug levels may cause side effects or reduced efficacy.

Additionally, solid forms often offer greater stability than liquid formulations. This stability helps maintain the integrity of the drug during storage and transportation and reduces the risk of quality degradation or loss of effectiveness. For example, some antibiotic tablets remain effective for long periods of time under a variety of environmental conditions, ensuring patients receive their medicines with optimal efficacy.

Additionally, the convenience and ease of administration associated with solid dosage forms contribute to improved patient compliance with treatment plans. Solid dosage forms, such as tablets or capsules, that are easy to transport and administer are more likely to adhere to prescribed treatment regimens than preparations that require precise dosing or special handling, such as suspensions or injections. Improved compliance ultimately improves treatment outcomes and reduces the likelihood of treatment failure or, in the case of antimicrobial agents, the development of drug-resistant strains.

The advantages of solid dosage forms, including precise dosing, controlled release, stability, and convenience, play an important role in ensuring the effectiveness and safety of pharmaceutical treatments. These characteristics are reflected in a variety of medicines in different therapeutic areas and generally help to improve patient outcomes and health care.

 

Ease of handling and processing:

In pharmaceutical manufacturing, powders and granules are often preferred because of their ease of handling and processing. Can be efficiently mixed, compressed, encapsulated and coated to produce final dosage forms.

Powders and granules are especially prized in pharmaceutical production because they are very easy to handle and process. Its intrinsic properties allow for smooth management in various production stages. A significant advantage is the efficient mixing capability to uniformly distribute the active pharmaceutical ingredient (API) and excipients. This homogeneity is essential to ensure consistent dosage and effectiveness of the final product.

Additionally, powders and granules can undergo a compression process, which is an important step in the production of solid dosage forms such as tablets and capsules. Through compression, these particulate materials can be converted into compressed units, providing precise dosing and ease of administration to patients. This process ensures equal distribution of the active ingredients within each dosage unit, reduces the risk of dosage fluctuations and ensures reliable treatment results.

In addition to compression, powders and granules offer encapsulation versatility, allowing them to be encapsulated in gelatin capsules or other suitable materials. Encapsulation is used for a variety of purposes, including taste masking, improving stability, and facilitating controlled drug release. For example, sustained-release capsules use polymer-coated granules to achieve sustained drug release and ensure constant plasma concentrations over a long period of time, improving patient compliance and treatment efficacy.

Additionally, coating powders and granules represents a critical step in pharmaceutical manufacturing and contributes to the aesthetics, stability, and efficacy of the product. Coatings can provide desirable properties such as improved palatability, taste masking, environmental protection, and modified release profiles. For example, applying an enteric coating to the granules ensures that the drug remains intact in the acidic environment of the stomach and is only released into the alkaline environment of the intestine, preventing stomach irritation and improving drug absorption.

To illustrate, consider making a multivitamin. First, the various vitamin and mineral powders are carefully mixed until a homogeneous mixture is obtained. This mixture is then compressed into tablet form to ensure precise dosing of each nutrient. The tablets can then be placed into gelatin capsules to improve their taste and make them easier to take. Finally, protective coatings can be applied to tablets to protect them from moisture and oxygen degradation, thereby extending shelf life and maintaining product quality.

Powders and granules are preferred in pharmaceutical manufacturing due to their advantageous properties including ease of handling, homogeneous mixing, suitability for compression and encapsulation, and versatility in coating applications. These properties allow the efficient manufacture of a variety of formulations with improved stability, efficacy, and patient acceptability.

 

Customization and Flexibility:

Pharmaceutical powders and granules can be tailored to specific patient needs, such as B. adjusting dosage strength or incorporating controlled release formulations.

Pharmaceutical powders and granules have tremendous flexibility that can be tailored to the individual needs of each patient. This customization involves a variety of adjustments, from fine-tuning dose strength to incorporating sophisticated controlled release mechanisms. Healthcare professionals can leverage this adaptive capacity to optimize treatment outcomes and improve patient compliance with prescribed treatments.

For example, imagine a scenario where a patient needs medication to treat chronic pain. The ability to customize pharmaceutical powders and granules allows pharmacists to carefully create formulations that exactly match the patient’s prescribed dosage, ensuring optimal efficacy and minimizing the risk of side effects. Additionally, by incorporating controlled release technology into the formulation, the drug can be released slowly over an extended period of time, providing long-lasting relief and potentially reducing dosing frequency.

As another example, let’s say a pediatric patient needs a drug that is not commercially available in an appropriate dosage. Pharmaceutical powders and granules offer the flexibility to adjust the concentration of active ingredients, allowing pharmacists to tailor formulations to the specific needs of children and ensure safety and effectiveness.

These customized formulations can also address issues such as a patient’s allergies or sensitivities to specific ingredients. By carefully selecting and excluding ingredients based on individual patient profiles, healthcare providers can reduce risk and improve treatment compliance.

The adaptability of pharmaceutical powders and granules allows healthcare professionals to provide customized treatment solutions to patients’ diverse needs and preferences, ultimately improving health outcomes and patient satisfaction.

 

Stability and Shelf Life:

Properly formulated powders and granules can improve the stability and shelf life of pharmaceutical products by preventing the active pharmaceutical ingredient (API) from decomposing or interacting with other ingredients.

Carefully formulated powders and granules play an important role in pharmaceutical formulations because they significantly increase the stability and shelf life of drugs. This is achieved through a multi-layer process where these special formulations act as a protective barrier, ensuring the integrity and effectiveness of the active pharmaceutical ingredient (API).

First of all, careful design of powders and granules ensures that the active ingredients are encapsulated in a stable matrix, protecting them from external factors such as moisture, light and oxygen, which can cause decomposition or chemical reactions. By providing this protective barrier, the formulation effectively minimizes the risk of degradation or alteration of the active ingredients over time, thereby preserving therapeutic efficacy.

Additionally, these formulations are designed to prevent interactions between the active ingredient and other ingredients contained in the drug. Some substances, such as excipients or fillers, can potentially react with the active ingredients, causing decomposition or producing unwanted by-products. Properly formulated powders and granules act as buffers and prevent direct contact between the active ingredients and these reactive substances. This reduces the risk of chemical reactions that can affect the quality and effectiveness of the drug.

To illustrate, let’s consider the example of vitamin supplements. Many vitamins are sensitive to light and moisture, which can cause them to deteriorate and become less effective over time. By encapsulating vitamins in carefully formulated powders or granules, pharmaceutical manufacturers can ensure that these sensitive compounds are protected from environmental influences, thereby extending the shelf life of supplements and maintaining their effectiveness until consumed.

Strategic formulation of powders and granules in pharmaceuticals is an important process to maintain drug stability and extend shelf life. By applying a protective barrier and preventing chemical interactions, these specialized formulations maintain the integrity and effectiveness of active pharmaceutical ingredients, ultimately providing safe and effective treatments for patients.

 

Improved bioavailability:

Some pharmaceutical compounds in crystalline form may have poor solubility or absorption. By converting them into powders or granules, pharmaceutical scientists can improve their bioavailability through techniques such as micronization or particle size reduction.

Some pharmaceutical compounds have problems with solubility or absorption in their crystalline state. These limitations may affect the effectiveness of therapeutic applications. However, pharmaceutical scientists have developed strategies to overcome these barriers. One approach is to convert these compounds into powders or granules to greatly improve their bioavailability.

The process of converting crystalline compounds into powders or granules involves various techniques such as micronization or particle size reduction. Micronization involves reducing the size of drug particles to microscopic levels, typically less than 10 micrometers. This technology increases the surface area of the particles, allowing for faster dissolution and absorption into the body. On the other hand, particle size reduction technology breaks down larger drug particles into smaller particles to improve solubility and absorption.

For example, consider poorly soluble pharmaceutical compounds used to treat certain diseases. The crystalline form may have limited dissolution in the gastrointestinal tract, resulting in insufficient absorption and reduced therapeutic efficacy. Using micronization, or particle size reduction techniques, pharmaceutical scientists can convert drugs into finely divided powders or granules. These smaller particles have a greater surface area to volume ratio and therefore dissolve more quickly when administered orally. This improves the bioavailability of the drug, providing better treatment outcomes for patients.

Converting crystalline pharmaceutical compounds into powders or granules using techniques such as micronization or particle size reduction represents a practical strategy to improve solubility and absorption. This approach highlights the expertise of pharmaceutical scientists in optimizing drug formulations to maximize therapeutic efficacy.

 

Taste masking and palatability:

Granules and powders incorporate flavoring and masking agents to improve the taste and palatability of orally administered drugs, especially for pediatric and geriatric populations.

Granules and powders serve as versatile vehicles to improve the overall palatability and acceptability of orally administered drugs, especially in vulnerable populations such as children and the elderly. By adding flavors to these formulations, pharmaceutical companies can alleviate the unpleasant taste associated with the drug, thereby improving patient compliance and treatment outcomes. Likewise, the inclusion of a masking agent neutralizes bitter or unpleasant tastes, making the medicine more palatable and easier to swallow.

For example, medication for children is often difficult because children dislike bitter tastes and strong smells. Pharmaceutical companies can make medications more appealing to children by producing them in granule or powder form and adding attractive flavors such as strawberry, grape, or orange, thereby increasing the likelihood of successful administration and compliance.

Likewise, the elderly population often has difficulty swallowing pills or tablets, creating problems with medication administration. By converting pharmaceuticals into easily dispersible granules or powders and incorporating masking agents to block off-flavors, pharmaceutical companies can improve the overall treatment experience for older adults. For example, powders with a pleasant mint flavor may mask the bitter taste of the active ingredient and may be better tolerated by elderly patients.

The use of granules and powders in drug formulations in combination with flavoring and masking agents represents a significant advance in improving the palatability and acceptability of orally administered drugs, especially for vulnerable populations such as children and the elderly. That’s right.

 

Versatility of delivery systems:

Powders and granules can be used in a variety of drug delivery systems, including immediate, modified, delayed, and targeted drug delivery systems, providing versatility in drug development.
Powders and granules are versatile materials with numerous applications in drug delivery systems. These materials offer a wide range of functionality in a variety of formulations and meet a variety of pharmaceutical requirements.

Immediate-release drug delivery systems utilize the rapid dissolution properties of powders and granules to ensure rapid onset of therapeutic effects following administration. Modified-release formulations use these components to control the release rate of the active ingredient, thereby extending the drug effect over a longer period of time. Sustained-release systems use the slow dissolution properties of powders and granules to maintain therapeutic drug levels in the bloodstream, minimize fluctuations, and optimize efficacy. Targeted drug delivery systems leverage the unique properties of these materials to precisely deliver drugs to specific locations in the body, improving treatment outcomes and minimizing side effects.

For example, consider the development of immediate-release painkillers. By formulating active ingredients in the form of fine powders or granules, pharmaceutical scientists can ensure rapid dissolution after ingestion, resulting in rapid relief for patients. In contrast, when formulating sustained-release diabetes medications, controlling the release of granules over time allows for consistent glycemic control throughout the day. Additionally, encapsulating cytotoxic agents in granules as part of targeted chemotherapy allows selective delivery to tumor tissue while sparing healthy cells, increasing treatment efficacy and reducing systemic toxicity.

Powders and granules serve as essential components in the formulation of various drug delivery systems, providing versatility and accuracy in drug development. Through strategic use, these substances will facilitate the development of drugs for a variety of therapeutic needs, ultimately improving patient outcomes and quality of life.

 

Quality Control and Assurance:

The production of pharmaceutical powders and granules requires rigorous quality control systems to ensure batch-to-batch consistency, purity, and safety of the final dosage form.
The production process of pharmaceutical powders and granules is characterized by meticulous implementation of quality control protocols. These measures are important to ensure the uniformity, purity, and safety of each batch of the final formulation.

In practice, this involves a series of rigorous tests and inspections at various stages of production. Raw materials are carefully tested to verify their quality and suitability for use. To ensure consistency during the manufacturing process, certain parameters such as temperature, pressure, and mixing time are carefully monitored and controlled.

Quality control also extends to the production stage and includes packaging and storage conditions. Packaging materials are tested to ensure they meet regulatory standards and do not compromise the integrity of the pharmaceutical product.

For example, consider a pharmaceutical company that produces tablets. Before production begins, active pharmaceutical ingredients (APIs) and excipients undergo rigorous testing to ensure their identity, purity, and potency. Throughout the mixing and granulation process, automated systems control precise parameters such as particle size distribution and moisture content.

Once formulated, each sample batch undergoes extensive testing for characteristics such as dissolution rate, content uniformity, and microbial contamination. Any deviation from specified specifications will initiate investigation and corrective action to maintain quality standards.

Ultimately, this commitment to quality control not only ensures the efficacy and safety of medicines, but also promotes trust between healthcare professionals and patients.

 

Cost-effectiveness:

Compared to other dosage forms, powders and granules can provide a cost-effective solution for pharmaceutical manufacturing, especially for bulk drugs.

Considering the various dosage forms of drugs, powders and granules have proven to be particularly advantageous in terms of economic efficiency in drug production, especially for drugs produced in large quantities. These benefits are due to several factors. First, the raw materials needed to produce powders and granules are often less expensive than other dosage forms such as tablets or capsules. This is because powders and granules generally require fewer processing steps and additives, reducing overall production costs. Additionally, powder and granule production processes are often simplified and streamlined, improving efficiency and reducing labor costs.

Additionally, the use of powders and granules allows for faster production, allowing manufacturers to more efficiently meet the high demand for certain drugs. This is particularly useful for drugs commonly prescribed or used in public health initiatives. Using powders and granules, manufacturers can optimize their production lines, reduce downtime and maximize production.

Additionally, the versatility of powders and granules makes it easy to adjust dosages and formulations to suit different patient needs. This flexibility is particularly useful in situations where precise dosing is essential or when dosing intensity may need to be altered to suit individual patient needs.

Defination of Powder and Granules

To illustrate, imagine a scenario where a pharmaceutical company is tasked with developing a commonly prescribed painkiller. By producing these drugs in powder or granular form, companies can benefit from the cost efficiencies associated with these formulations. They can effectively meet market demand by using bulk purchasing of raw materials, streamlining the manufacturing process, and increasing production speed. Dosage can also be customized, allowing the drug to be available to a wider range of patients, improving patient access and compliance.

Basically, the cost-effectiveness and practical advantages of powders and granules make them an attractive choice for pharmaceutical manufacturers, especially when producing large quantities of drugs. Simplicity, efficiency and versatility help simplify manufacturing processes while ensuring patient accessibility and convenience.

In summary, powders and granules play an important role in the pharmaceutical industry as they facilitate drug formulation, improve dosage uniformity, improve bioavailability, and provide versatility in drug delivery systems while maintaining quality and efficiency of cost.

Importance of Powders and Granules in Pharmaceutical Sector Read More »

What is cGMP?

What is cGMP?, cGMP stands for “Current Good Manufacturing Practice” and is a set of rules and guidelines that ensure the quality, safety, and effectiveness of pharmaceutical products. These regulations are enforced by regulatory authorities such as the Food and Drug Administration (FDA) in the United States, the European Medicines Agency (EMA) in Europe, and similar authorities around the world.

 

From a pharmaceutical company’s perspective, cGMP compliance is critical to the manufacturing, testing, and distribution of pharmaceuticals and other pharmaceutical products. The primary purpose of cGMP is to reduce risks associated with manufacturing pharmaceutical products that cannot be eliminated through final product testing and to ensure that products are of high quality and consistently meet their intended purpose.

 

Basic principles of pharmaceutical CGMP:

List of particulars
  • Quality Control
  • Documentation and records
  • Personnel
  • Facilities and Equipment
  • Raw materials and ingredients
  • Production and process control
  • Packaging and Labeling
  • Testing and Quality Assurance

 

Quality Control:

A comprehensive quality management system monitors all aspects of production, from raw material procurement to product launch. A pharmaceutical company employs a quality management team responsible for regular audits, cGMP compliance, and continuous process improvement.
Our holistic approach to quality management systems is aligned to carefully monitor all aspects of the manufacturing life cycle, from raw material sourcing to final product launch. In the pharmaceutical industry, dedicated quality control teams play a critical role in maintaining the highest standards throughout the manufacturing process.

This team is tasked with conducting regular audits to assess compliance with strict quality protocols. For example, we carefully inspect manufacturing facilities and ensure they comply with current good manufacturing practices (cGMP), key regulatory guidelines designed to ensure the safety, effectiveness, and quality of pharmaceutical products. These checks may include testing production equipment, assessing facility cleanliness, and verifying documentation for accuracy.

Additionally, Quality Management is committed to encouraging a culture of continuous improvement within the company. This is not only about solving existing problems, but also actively identifying opportunities for improvement in various operational processes. For example, the team may regularly review manufacturing processes, evaluate the effectiveness of the quality management system, and implement corrective actions to address deviations from established standards.

In addition to audits and process improvement, quality management teams play an important role in risk management. They are involved in assessing potential risks during production and implementing preventive measures to mitigate these risks. This can include robust testing protocols, rigorous supplier qualification processes, and developing contingency plans to address unexpected issues.

Additionally, our comprehensive quality management system goes beyond manufacturing to encompass the entire supply chain. By working with suppliers to conduct thorough inspections and set clear quality expectations, the team can ensure consistent raw material quality. This active collaboration with suppliers helps prevent problems associated with adulterated ingredients and contributes to the overall reliability of the pharmaceutical supply chain.

In essence, implementing a comprehensive quality management system in pharmaceutical companies is not just a regulatory requirement, but a strategic imperative. It serves as a safeguard for consumers, a driver of operational excellence, and an active process for continuous improvement in an industry where precision and reliability are paramount.

Documentation and records

Rigorous documentation of all production processes, including raw material testing, production steps and quality control systems. To ensure traceability and accountability, detailed batch records are maintained for each production run, documenting every step from raw material testing to equipment calibration.

Thorough documentation of the manufacturing process is an essential practice that includes various aspects such as raw material testing, manufacturing steps, and a rigorous quality control system. This comprehensive approach includes carefully maintaining detailed batch records for each production run, providing a complete view of all steps performed. From initial inspection of raw materials to rigorous testing and precision calibration of equipment, this document serves as a careful roadmap to ensure traceability and accountability at every step of the manufacturing process.

To illustrate this, imagine a pharmaceutical manufacturing facility that maintains strict documentation practices. Before starting the production cycle, the facility conducts extensive testing to ensure the quality of incoming raw materials and compliance with established standards. These tests are carefully documented and record important parameters such as chemical composition, purity, and potency.

Once production begins, each step is documented in a batch record, including details of equipment used, environmental conditions and specific procedures. For example, when manufacturing tablets, batch records include details about the exact amount of each ingredient, the mixing and granulation process, and the compression and coating of the tablets.

The quality management system is fully integrated with the documentation process. Regular checks are carried out throughout production and the results are recorded in the batch log. Deviations from predetermined specifications result in immediate corrective action, which is carefully documented to ensure transparency and traceability.

Documentation also extends to equipment calibration, where facilities maintain records of routine checks and adjustments to ensure the accuracy and reliability of production machines. This proactive approach not only ensures product compliance but also helps you meet regulatory requirements.

The overall goal of this rigorous documentation is to establish a robust system that ensures the quality and safety of manufactured products. This not only enables efficient troubleshooting and root cause analysis of deviations, it also provides comprehensive historical documentation that is invaluable for continuous improvement planning and regulatory audits. In essence, practicing thorough documentation during manufacturing is the foundation for achieving excellence, maintaining product integrity, and complying with industry standards.

Personnel

Adequate staff training and qualification programs paying particular attention to good hygiene practices and compliance with dress codes. Regular training and skills assessments on cGMP principles are conducted for manufacturing personnel to ensure ongoing compliance with best practices.

An extensive staff training and qualification plan has been undertaken to teach proper hygiene practices and place great emphasis on staff compliance with the dress code. To promote a culture of excellence, we regularly organize training courses for production staff, paying particular attention to the principles of Current Good Manufacturing Practice (cGMP). These sessions go beyond basic compliance and address the complexities of maintaining high standards in a production environment.

To illustrate, let’s consider a pharmaceutical manufacturing plant. In these environments, employees undergo a rigorous training program that covers not only the theoretical aspects of cGMP, but also practical demonstrations of good hygiene practices. Employees are trained on the importance of maintaining a sterile and controlled environment to ensure the quality and safety of medications.

Skills assessments are conducted regularly as part of the qualification process. The goal of this assessment is to assess the employee’s ability to apply acquired knowledge and skills in real-world situations. For example, you can assess the ability of production workers to follow strict procedures and maintain sterility during the manufacturing process.

Additionally, continuous improvement is emphasized through ongoing training that addresses evolving industry standards and technological advancements. This proactive approach keeps production staff up to date with the latest developments, contributing to ongoing compliance with best practice.

In essence, the combination of in-depth initial training, regular skills assessments and ongoing training creates a strong structure that enables employees to maintain high levels of hygiene and dress code compliance, ultimately building a culture of excellence and compliance in production operations. .

Facilities and Equipment:

We regularly verify and calibrate our facilities and equipment to ensure they meet the standards required to manufacture pharmaceutical products. Regular validation of production equipment such as tablet presses or sterilization units is performed to ensure optimal performance and compliance.

Regular verification and calibration processes are essential in the pharmaceutical industry to ensure that systems and devices always meet specific standards. These procedures include systematic testing and tuning of various manufacturing components to ensure accuracy, reliability, and compliance with regulatory requirements.

In pharmaceutical manufacturing, regular validation of critical equipment plays a critical role in maintaining optimal performance and meeting stringent quality standards. For example, consider a tablet press, a critical tool in the production of pharmaceutical tablets. Validation of a typical tablet press includes a thorough evaluation of accuracy, uniformity, and dosing accuracy. By performing these verifications at predetermined intervals, manufacturers can identify and resolve deviations from desired specifications, ensuring consistent production of high-quality tablets.

Likewise, sterilization devices, which are essential for maintaining the sterility of pharmaceutical products, are regularly validated to ensure effectiveness. This involves evaluating parameters such as temperature, pressure, and exposure time to effectively remove potential contaminants during the sterilization process. Following a regular calibration and validation program can help pharmaceutical manufacturers reduce the risk of equipment failure, product quality deviations, and non-compliance with regulatory standards.

In summary, systematic verification and calibration of systems and equipment in pharmaceutical production not only serves as a proactive measure to prevent deviations, but also contributes to sustainable compliance with quality standards and ultimately ensures safe and effective pharmaceutical production.

Raw materials and ingredients

We strictly control the quality and integrity of raw materials and components used in the production process. Incoming raw materials are thoroughly tested and inspected to ensure they meet established quality standards before being used in production.

Strict measures are taken to maintain the quality and integrity of the raw materials and components used in the manufacturing process. Incoming raw materials undergo extensive testing and inspection procedures before being incorporated into the production line to ensure that they comply with specified quality standards.

For example, in the automotive industry, where precision and reliability are key, manufacturers carefully test raw materials such as metals and polymers that make up critical components such as engine parts and safety features. These materials undergo a series of tests including stress testing, dimensional analysis, and material composition evaluation. This ensures that only materials that meet rigorous quality standards are used in vehicle production, ultimately contributing to the overall durability and safety of the end product.

The will to strengthen regulations is not limited to manufacturing but is also evident in the pharmaceutical sector. In pharmaceutical manufacturing, raw materials used in drug formulations undergo extensive testing for purity, potency, and composition. Such accurate testing is essential to ensure that the medicines produced are not only effective, but also safe for consumption, thereby protecting the health and well-being of end users.

In essence, strict control over raw materials and ingredients is a common practice in a variety of industries and constitutes an important basis for the production of high-quality, reliable and safe products.

 

Production and process control

Controls are implemented during manufacturing to ensure consistency and quality of the final product. Continuously monitor and adjust manufacturing processes based on real-time data to maintain product quality and meet specifications.
Integrating rigorous controls throughout the manufacturing process is essential to ensure consistency and excellence of the final product. This includes continuously reviewing and fine-tuning manufacturing processes in response to real-time data, striving to maintain product quality, and strictly adhering to predetermined specifications. Let’s consider this concept further with a real-world example.

Imagine a high-tech electronics manufacturing plant producing cutting-edge smartphones. Strict controls are carried out at various stages of production to ensure consistent quality of each device. An important control measure is regular inspection of parts and materials before assembly. This is an automated system that detects errors or deviations from established standards. For example, optical sensors can detect defects in smartphone screens or electronic components and trigger immediate alerts for corrective action.

Real-time data analysis occurs as the assembly line moves. Each production station is equipped with sensors and monitoring devices that collect data on key performance indicators such as production speed, defect rate, and quality parameters. This data is continuously fed into a central system so that production managers can assess the state of the production process at any time.

Let’s say your real-time data shows slight deviations in the temperature settings of a particular manufacturing station that could potentially impact the quality of the final product. Automatic controls intervene to adjust temperature settings and ensure the production process remains within specified parameters. This proactive approach is consistent with the company’s commitment to preventing the production of low-quality smartphones and providing customers with high-quality products.

By integrating these controls and using real-time data, manufacturing plants not only ensure product consistency, but also improve overall efficiency. This example highlights the importance of dynamic monitoring and adjustments to maintain product quality and meet specifications throughout the entire manufacturing life cycle.

 

Packaging and Labeling

Ensure packaging and labeling meet established requirements and are consistent with the intended use of the product. We regularly test our packaging materials and labeling processes to avoid errors and ensure compliance with legal standards.
Compliance with specific packaging and labeling specifications is essential to ensure that the product is perfectly suited for its intended use. This includes regular inspections of packaging materials and labeling processes to proactively identify and correct potential defects. These stringent measures not only help maintain product quality and integrity, but also play a critical role in meeting regulatory standards.

For example, in the pharmaceutical industry where accuracy and precision are critical, ensuring packaging and labeling meets specific requirements is critical to both consumer safety and regulatory compliance. Packaging materials such as blisters, bottles and labels are inspected regularly to ensure they comply with established guidelines. This not only prevents the risk of misinformation, but also protects against potential health risks.

Additionally, in the food and beverage industry where consumer trust is paramount, compliance with packaging and labeling standards is essential. Regularly inspecting packaging, including labels, barcodes, and nutritional information, ensures that products are delivered to consumers with accurate and reliable information. This not only increases customer trust, but also ensures that your company complies with industry regulations.

In essence, close monitoring of packaging and labeling processes, supported by regular inspections, serves as a proactive approach to quality assurance and compliance in all industries. By adhering to these standards, companies can strengthen their reputation, increase consumer trust, and reduce the risk of legal repercussions.

 

Testing and Quality Assurance

We verify identity, resistance, quality and purity through in-depth testing of raw materials, work-in-progress samples and finished products. Our quality control laboratory performs a series of tests, including potency testing and microbial testing, to ensure that each batch meets required standards before release.

What is GMP?

Ultimately, cGMP compliance is important not only for regulatory approval but also for maintaining public trust in the pharmaceutical industry. Practical implementation of CGMP principles is demonstrated through careful documentation, a strong quality management system, and a commitment to continuous improvement and employee training. Failure to comply with cGMP can result in regulatory action, product recalls, and loss of confidence in the safety and effectiveness of your drug product.

What is cGMP? Read More »

Transportation System Validation for Pharmaceutical Products

Transportation System Validation, In the past, legalizing the transport of pharmaceuticals was not important, but today it is encouraged by all major regulatory authorities. Storage conditions must be checked when transporting medicines as this may affect the stability of the medicine.

When storing medications in a manufacturing facility or medical specialty store, it is recommended to maintain a controlled environment. It is also important to transport these products under certain controlled conditions.

As temperature rises, the effectiveness of the drug may decrease. While transporting these items, there is a risk of temperature changes due to various factors. Therefore, the entire transport process must be verified. Before starting the verification process, a verification protocol must be created.

It has been observed that a 20% increase in temperature can reduce drug effectiveness by up to 25% when stored at 2-8°C. Each drug has its own unique relationship between temperature and reduced effectiveness. This can only be decided individually. As we all know, most vaccines can deteriorate if mishandled during transportation and storage.

According to WHO, 25% of vaccines are found to be ineffective once they reach their destination due to uncontrolled temperatures. WHO TRS961 Annex 9 recommends transport of medicinal products under controlled temperature conditions. Any deviations must be reported to the dealer and investigated. The European Commission has also published a brief guide on transport verification.

Temperature-controlled vehicles are used to transport pharmaceuticals. These vehicles must be tested under controlled environmental conditions before use. The temperature and humidity of the compartment must be recorded for a period equal to the actual transit time of the product. The time required to exceed the maximum storage temperature and humidity in case of control failure should also be determined by considering the worst-case scenario.

During transport, temperature and humidity data loggers are used to record temperature and humidity. Data loggers are placed in various locations with the product. Sometimes data loggers may be included in the product to capture actual data. This should be done in both warm and cold seasons.

A risk assessment should be performed for various factors during transport, such as data recorder failure, vibration, delays during transport, and other factors that may occur during transport. Impact measurement stickers can be used to test impact sensitive materials. Drivers must be trained on how to use data recording devices while driving. Steps are

  • Define Validation Scope and Objectives
  • Develop Validation Plan
  • Risk Assessment
  • Select Suitable Transportation Equipment
  • Temperature Mapping and Monitoring
  • Documentation and Standard Operating Procedures (SOPs)
  • Qualification of Transportation Partners
  • Performance Qualification (PQ)
  • Data Analysis and Reporting
  • Review and Approval
  • Continuous Monitoring and Revalidation
  • Regulatory Compliance

Steps of Transportation System Validation

Transport system Validation is an important aspect of ensuring the integrity and quality of pharmaceutical products during their transport from the point of manufacture, through distribution, and all the way to the end user. The validation process involves ensuring that the transport system consistently and effectively maintains the conditions required for the storage and transport of the drug. The main steps in performing pharmaceutical transport system validation are:

 

Define Validation Scope and Objectives

Clearly define the scope and objectives of Transportation System Validation. Identify important parameters and requirements for pharmaceutical transport, including: B. Temperature, humidity and light protection.

To ensure smooth transport of pharmaceuticals, it is essential to accurately formulate Transport System Validation parameters and objectives. It is important to clearly define the scope of this verification process to maintain the integrity and functionality of the transported product. Careful assessment is required to identify critical parameters and specific requirements during pharmaceutical transport.

To understand the full extent of a Transportation System Validation, it is first necessary to describe the entire journey of a pharmaceutical product from origin to final destination. It involves various steps and procedures, including physical movement as well as storage, handling, and transshipment. Presenting these aspects clearly helps create a complete framework for the verification process.

Additionally, Transportation System Validation goals should include end-to-end quality assurance as well as compliance, safety, and risk mitigation considerations. Transportation System Validation not only ensures the physical safety of the drug product, but also meets regulatory requirements from health authorities and industry standards.

Careful study of environmental factors is necessary to identify critical parameters that may affect pharmaceuticals during transport. This includes, among other things, protection from temperature, humidity and light. Extensions of this concept include defining acceptable ranges for these parameters and developing contingency plans or corrective strategies in case of deviations. A rigorous monitoring system must be put in place to ensure that these critical parameters are maintained within established limits throughout the transport process.

Additionally, the requirements for pharmaceuticals during transport go beyond environmental conditions. Packaging standards, safety protocols, and shipping documentation must be carefully considered. This includes setting specifications for packaging materials that protect the product from external influences, implementing security measures to prevent theft or tampering, and ensuring that all required documents, such as delivery manifests and certificates of conformity, remain with the product throughout its journey.

To ensure the quality, safety and regulatory compliance of pharmaceutical products during transport, a robust and comprehensive approach that defines the scope and purpose of transport system validation and an in-depth analysis of critical parameters and requirements are essential.

 

Develop Validation Plan

Develop a comprehensive Validation plan that describes the procedures, responsibilities, and schedule for verification activities. This plan should include details about the verification team, testing procedures, acceptance criteria, and documentation requirements.

Develop a comprehensive verification strategy that includes a detailed framework outlining assigned procedures, roles and responsibilities and a carefully developed program for conducting verification activities. This comprehensive plan should address the details of the verification team, describe the complexities of the test procedures, establish rigorous acceptance criteria, and clarify documentation requirements.

When developing this validation plan, it is essential to describe the overall methodology that will be used to validate the intended process, system, or product. Clearly define the roles and responsibilities of each member of the verification team to streamline and coordinate work. Consider the chronological order of verification activities and create a detailed schedule that provides a roadmap for the entire verification process.

The plan should describe the composition of the validation team and outline the skills and competencies of each member to ensure a complete and capable team capable of managing the various aspects of the validation process. It specifies the test methods to be used and emphasizes a systematic and thorough approach to verifying the performance, reliability, and validity of the object under investigation.

Establish clear acceptance criteria that serve as a measure of success for the verification process. To ensure that verification activities actually meet established standards, these criteria must be rigorous and tailored to the desired results. At the same time, it outlines documentation requirements and provides a structured framework for recording and archiving the verification process, results, and identified deviations.

By developing and following this comprehensive verification plan, your organization can systematically and rigorously ensure the quality, compliance, and reliability of the process, system, or product in question, creating a solid foundation for success.

 

Risk assessment

We carry out risk assessments to identify potential risks associated with the transport process. This includes assessing the impact of temperature fluctuations, delays and other factors that can affect product quality. Mitigation strategies should be developed for the identified risks.

By carrying out a comprehensive risk assessment, we identify and carefully evaluate potential risks closely related to the transport process. This requires thorough investigation of various aspects, including the impact of temperature fluctuations, potential delays, and other factors that may affect the overall quality of the transported product. It is important to explore the complexities of each stage of the transport journey to identify vulnerabilities and uncertainties.

If there are temperature fluctuations, a detailed analysis must be performed to understand how temperature fluctuations may affect the integrity and performance of the product being transported. The specific temperature requirements of the product must be taken into account and the potential for deviations during transport assessed. Additionally, the potential consequences of temperature fluctuations, from reduced product quality to safety issues, must be thoroughly studied.

Delays, another important aspect of the shipping process, deserve careful investigation. This includes investigating possible causes of delays, such as logistics issues, traffic congestion or unforeseen circumstances. When developing a comprehensive risk mitigation strategy, it is best to understand the potential impact of delays on product quality and overall supply chain efficiency.

Various factors that can affect product quality during transport must also be considered. This includes handling practices, storage conditions, and general environmental conditions to which the product may be exposed. A holistic approach to risk assessment involves examining the complexity of these factors to fully understand potential threats to product quality.

Once these risks are identified, the next essential step is to develop a robust mitigation strategy. These strategies should be tailored to the specific risks identified during the assessment process. For example, implementing temperature-controlled packaging, creating contingency plans for potential delays, and optimizing handling and storage protocols are potential components of an effective risk mitigation strategy.

A careful risk assessment of a transportation process is more than simply identifying potential hazards. This includes a comprehensive examination of the complexities and interactions within the supply chain. This approach lays the foundation for the development of targeted and effective mitigation strategies that protect the integrity and quality of transported products.

 

Select Suitable Transportation Equipment

Depending on the specific requirements of your pharmaceutical product, choose an appropriate transportation method such as insulated containers, refrigerated trucks, or temperature-controlled storage facilities. Ensure your equipment meets regulatory standards and guidelines.

When handling pharmaceuticals, choosing the right transport equipment is important and factors such as product sensitivity and regulatory compliance must be carefully considered. The optimal option may include insulated containers, refrigerated trucks or temperature-controlled storage facilities, each tailored to the individual needs of pharmaceutical transport.

For example, vaccines often require cold, constant temperatures to remain effective. Therefore, choosing a refrigerated vehicle equipped with an advanced temperature monitoring system ensures that the integrity of the vaccine is maintained throughout the journey. Not only does it comply with industry regulations, but it also protects the health and well-being of end users.

Likewise, drugs sensitive to extreme temperatures may benefit from insulated containers that provide a protective environment. These containers act as a shield against external temperature fluctuations, ensuring a stable internal climate and protecting the medicine from decomposition.

Compliance with regulatory standards is critical in the pharmaceutical industry. Transport equipment must not only be selected based on specific product requirements, but must also meet strict regulatory guidelines. This includes adhering to international standards such as Good Distribution Practices (GDP) to ensure the quality, safety and effectiveness of pharmaceuticals during transport.

Careful selection of transportation vehicles, whether insulated containers, refrigerated vehicles, or temperature-controlled storage facilities, highlights our commitment to product integrity and regulatory compliance. This approach not only mitigates the risks associated with temperature-sensitive drugs, but also highlights the industry’s commitment to providing safe and effective products to end users.

 

Temperature mapping and monitoring

Temperature mapping studies are performed to assess temperature distribution within transportation systems. Temperature sensors are placed in critical locations to monitor and record temperature fluctuations during driving. Continuous monitoring during actual transportation is also essential.
To comprehensively assess the temperature distribution within a transportation system, it is essential to conduct a temperature mapping study. Temperature sensors are strategically placed at key locations to systematically monitor and record temperature fluctuations throughout your trip. This method allows a detailed understanding of thermal conditions during transport.

For example, temperature mapping studies play an important role in the pharmaceutical industry, where the integrity of some drugs is very sensitive to temperature fluctuations. Temperature changes that occur during pharmaceutical transport can be monitored by strategically placing temperature sensors in critical areas of the transport system, such as storage rooms and cargo holds. This careful monitoring ensures that the prescribed temperature range is maintained and the transport capacity and effectiveness of the drug is ensured.

The importance of continuous monitoring during actual transport cannot be underestimated. This real-time data collection allows for immediate intervention in case of deviations from the desired temperature range. For example, if a refrigerated truck transporting perishable goods experiences a temporary malfunction, a continuous monitoring system can immediately alert those involved and take corrective action to prevent product loss or damage.

Performing temperature mapping studies using strategically placed sensors and ensuring continuous monitoring during transportation not only provides a comprehensive understanding of temperature dynamics within the system, but also allows stakeholders to proactively address potential problems, thereby Reliability and quality improve.

 

Temperature Mapping

Temperature mapping is a critical process when transporting pharmaceuticals, especially those that require strict temperature control to maintain efficacy. The steps involved in temperature mapping for a pharmaceutical company’s product transportation system are as follows:

  • Define Temperature Requirements
  • Select Monitoring Devices
  • Identify Critical Control Points (CCPs)
  • Placement of Monitoring Devices
  • Pre-Conditioning of Containers
  • Data Logger Calibration
  • Record Baseline Data
  • Real-time Monitoring
  • Simulate Extreme Conditions
  • Data Analysis
  • Generate Reports
  • Continuous Improvement
Define temperature requirements

Check temperature specifications for each drug product being transported. Each product may have a different temperature range that must be maintained to ensure stability and performance.
Determine the specific temperature requirements for each drug product during transport, as different products often require different temperature ranges to maintain stability and effectiveness. Carefully identifying and adhering to these temperature specifications is important to ensure drug product integrity throughout the supply chain.

For example, vaccines that are highly sensitive to temperature changes require strict temperature control during transport. Vaccine cold chain management is important to maintain vaccine effectiveness. If the vaccine is exposed to temperatures outside the recommended range, it may become less effective and may reduce immunity. This is especially true for some mRNA vaccines, such as COVID-19 vaccines, which require extremely cold temperatures to preserve their molecular structure for storage and transport.

On the other hand, some biological products or temperature-sensitive drugs may require room temperature control to prevent denaturation or degradation. Failure to maintain specified temperature conditions for these products during transport may result in reduced therapeutic efficacy and, in some cases, potential harm to patients dependent on these medications.

Therefore, a comprehensive understanding of the different temperature requirements of different drugs is essential to develop effective delivery strategies. The application of sophisticated temperature monitoring systems, the use of insulated packaging and the use of special transportation methods are essential components to ensure that pharmaceutical products reach their destination with their quality and efficacy intact. This careful approach not only meets regulatory standards, but also protects public health by ensuring medicines are delivered as intended.

 

Select your monitoring device

Select an appropriate temperature monitoring device, such as a data logger or sensor. These devices must be able to accurately record and store temperature data throughout the transport process.

Selecting the right temperature monitoring device, such as a data logger or sensor, is critical to maintaining the integrity of temperature-sensitive products during transportation. These devices contribute significantly to ensuring the quality and safety of transported products by continuously maintaining specific temperature conditions.

A practical example of the importance of temperature monitoring can be found in the pharmaceutical industry. Many drugs and vaccines require strict temperature control to maintain their effectiveness. During transport, these delicate pharmaceuticals must be stored within a specific temperature range to prevent decomposition. Using data loggers or advanced sensors, you can monitor the temperature status of your containers or vehicles in real time. If the temperature falls outside the acceptable range, the monitoring device will trigger an alarm and take immediate corrective action. This proactive approach helps prevent drugs from losing their effectiveness due to temperature changes.

Additionally, when choosing a temperature monitoring device, you must consider the specific requirements of your transported products and supply chain logistics. For example, in the food industry transporting perishable goods, precise temperature monitoring is essential to prevent spoilage and ensure food safety. Data loggers with wireless connectivity can transmit real-time temperature data to a central system, allowing interested parties to immediately check product status throughout the journey.

Choosing an appropriate temperature monitoring device is not only a technical consideration, but also an important aspect of ensuring product quality and safety during transportation. Choosing equipment to suit the individual needs of your industry and the transportation of goods increases the reliability and efficiency of your entire supply chain.

 

Identify critical control points (CCPs)

Determine critical control points within the transportation system where temperature fluctuations may occur. This may include loading areas, storage areas, transport vehicles and unloading areas.
Identify key nodes in the transportation system where temperature fluctuations may pose risks. These critical control points include loading areas, storage rooms, transport vehicles, and unloading areas, each of which plays a critical role in maintaining the integrity of temperature-sensitive cargo during transportation.

In the loading area, care must be taken to determine the duration and conditions under which the product will be exposed to ambient temperatures. For example, when transporting pharmaceuticals, some drugs or vaccines may have stringent temperature requirements and loading procedures must ensure smooth transfer from storage location to vehicle without compromising efficiency.

Storage spaces, warehouses or transportation represent another important control point. Consider transporting perishable items in a refrigerated vehicle. Monitoring and maintaining specific temperatures in these compartments is essential to prevent damage or spoilage of products such as fresh produce or dairy products.

The vehicle itself forms an important link in the temperature control chain. Maintaining your cooling system or climate control feature is essential to maintaining the desired temperature throughout your trip. For example, transporting frozen foods can result in significant inventory loss due to failure of refrigeration units during transport.

The unloading area represents the last boundary where products are exposed to temperature fluctuations. Ensuring fast and efficient unloading operations minimizes the time products are exposed to various environmental conditions and reduces the risk of temperature-related damage. For example, when transporting sensitive electronic components, it is important to keep temperature extremes as low as possible during extraction to preserve the functionality of these products.

Identifying and addressing critical control points within transportation systems associated with temperature fluctuations is critical to ensuring the quality and integrity of a variety of products during transportation. Real-world examples from a variety of sectors demonstrate the importance of a holistic approach to temperature management throughout the transport process.

 

Placement of Monitoring device 

Place monitoring devices at strategically identified critical control points. Make sure it is evenly distributed to capture temperature fluctuations in various areas of the conveyor system.
Implement a carefully planned strategy by strategically placing monitoring devices at key critical control points within your transportation system. To effectively detect and monitor temperature fluctuations in various areas, it is important to ensure uniform distribution of these devices. This meticulous attitude goes a long way in ensuring comprehensive monitoring of the entire transport network, enabling a proactive approach to resolving potential problems and ensuring the integrity of sensitive cargo or perishable goods.

For example, in the context of cold chain logistics systems where maintaining specific temperature conditions is important for the transport of pharmaceuticals or fresh produce, it is important to place monitoring devices at critical control points such as loading docks, storage areas and transport compartments. Orientation work. Strategically placed these devices allow immediate detection of temperature fluctuations or deviations from required conditions. This allows timely intervention, such as adjusting climate control settings or redirecting transport, to ensure the quality and safety of transported products.

The strategic implementation of monitoring devices at critical control points is not only a logistical necessity that emphasizes active distribution, but is also a proactive system that increases the efficiency and reliability of the entire transportation system, especially in industries with maximum compliance with specific environmental conditions.

 

Pre-Conditioning of Containers

If necessary, establish preconditioning to ensure that containers or vehicles used for transport are at the required temperature prior to loading the drug product. This step is very important to prevent rapid temperature changes.
Where appropriate, it is essential that containers or vehicles used to transport pharmaceuticals are properly conditioned to reach and maintain the required temperature before loading begins. This critical step is essential to prevent sudden thermal shock that can compromise the integrity and effectiveness of sensitive pharmaceuticals.

For example, imagine a scenario where a pharmaceutical company is transporting a vaccine that requires strict temperature control to maintain its effectiveness. Before loading these vaccines onto refrigerated trucks, it is important to pre-condition the vehicles to the recommended temperature range. This essential process carefully establishes temperature controls and ensures that the environment inside the containers meets the conditions specified for safe transport of the vaccines.

If these precautions are not taken, the vaccine may be exposed to rapid temperature changes during transport, potentially causing the vaccine to deteriorate or lose efficacy. The consequences of this thermal shock can be serious, affecting the quality and safety of medicines, making them unusable or even posing a threat to public health.

By pre-certifying containers or transport vehicles, companies demonstrate their commitment to meeting the rigorous standards required for pharmaceutical logistics. This proactive approach not only protects transported products, but also maintains the trust of consumers, regulators, and other stakeholders in the pharmaceutical supply chain. In essence, this careful preconditioning process serves as proactive protection against temperature-related hazards and ensures the safe and successful transport of pharmaceutical products from the manufacturing site to the end user.

 

Data logger calibration

Calibrate data loggers or temperature sensors before use to ensure accuracy. To ensure the reliability of temperature data, regular calibration tests must also be performed.
It is important that all data loggers and temperature sensors undergo a thorough calibration procedure before use to ensure the accuracy of temperature readings. Additionally, regular calibration checks must be incorporated into operating protocols to maintain the reliability and accuracy of temperature data over time.

Calibration is an important step to verify the accuracy of temperature measurements obtained from a data logger or sensor. Calibration essentially compares the readings of a device to a known standard or reference to identify and correct any deviations. By calibrating these instruments before first use, companies can establish a baseline level of accuracy so that subsequent temperature readings can be reliable and meet accepted standards.

As an example, consider a pharmaceutical company that relies on temperature-sensitive storage of vaccines. To ensure the vaccine is effective and safe, the company uses data loggers to monitor and record temperature conditions. A thorough calibration process is performed before this recorder is used. This involves placing the recorder in a controlled environment with a known stable temperature, comparing the recorded data to expected values, and making adjustments as necessary to bring the readings to the set values.

Additionally, regular calibration checks are essential to prevent potential drift or loss of accuracy of data loggers or temperature sensors. Over time, factors such as wear and tear, environmental conditions, and aging of electronic components can affect the performance of these devices. Implementing routine calibration checks allows you to immediately identify and address deviations from desired accuracy, eliminating the risk of inaccurate temperature data that could compromise the quality of stored vaccines or other temperature-sensitive products.

Active calibration procedures not only ensure the accuracy of temperature measurements upon first use, but also play an important role in maintaining reliability throughout the life of the data logger and temperature sensor. This pursuit of precision is especially important in industries where precise temperature control is essential to maintain the integrity of the product or material.

 

Record Baseline Data

Record baseline temperature data at each observation point before starting the transport process. We provide reference material to compare transportation travel.

Before starting the transport process, it is important to carefully document baseline temperature data at each monitoring point. These meticulous records serve as an important reference point and enable comprehensive comparisons at different stages of the transport journey. This careful approach allows any deviations from established temperature standards to be immediately identified and corrected, ensuring the integrity and quality of transported products.

For example, consider the pharmaceutical industry, which requires strict temperature control when transporting sensitive drugs. By recording baseline temperature data at the point of origin and at each monitoring point in the supply chain, pharmaceutical companies can monitor and analyze temperature conditions to ensure that medicines reach their destination in optimal condition. When deviations occur, immediate corrective action can be taken to reduce the risk of product degradation.

This approach applies beyond the pharmaceutical industry to sectors as diverse as food distribution, where maintaining the freshness and safety of perishable products is critical. By identifying baseline temperature data, food companies can systematically monitor and respond to temperature fluctuations, reducing the risk of spoilage and providing consumers with the highest quality product.

Recording basic temperature data acts as a proactive measure, enabling real-time monitoring and intervention, ultimately contributing to the overall success of the transport process and maintaining product quality.

 

Real-time monitoring

If possible, implement a real-time monitoring system to continuously monitor temperature changes. This allows immediate corrective action in case of deviations from specified temperature ranges.

Establishing a real-time monitoring system is important to maintain a proactive approach that continuously monitors temperature changes. By implementing these systems, companies can ensure rapid response to deviations from predetermined temperature ranges, improving operational efficiency and product quality.

For example, in the pharmaceutical industry, where strict temperature control is essential for the storage of vaccines and drugs, real-time monitoring systems play an important role. The system continuously monitors temperature fluctuations within the storage facility. If the temperature falls outside the specified range, an alert is immediately issued requiring immediate corrective action, such as adjusting the cooling system or relocating sensitive products to prevent spoilage.

Additionally, a real-time temperature monitoring system is essential in terms of food storage and distribution. In cold chain logistics, maintaining the optimal temperature of perishable products is very important. Implementing a monitoring solution ensures that discrepancies are immediately addressed, preventing potential spoilage and preserving the integrity of food throughout the supply chain.

The use of a real-time temperature control monitoring system is not only a preventive measure against deviations, but also serves as a proactive tool for companies to maintain quality standards and regulatory compliance in industries where accurately controlled temperatures are critical.

 

Simulate extreme conditions

Perform simulations or tests under extreme conditions such as: B. Ensure that the transport system is capable of maintaining the required temperature levels under a variety of conditions, whether through high ambient temperatures or long transport times.
It is important to conduct simulations or tests in challenging environments such as: B. When the transport system is exposed to high ambient temperatures or is transported for long periods of time. This is done to ensure reliability and resilience under real-world conditions by verifying the system’s ability to consistently maintain a given temperature level under a variety of conditions.

For example, imagine a pharmaceutical company transporting a temperature-sensitive vaccine to a remote area in a harsh climate. To verify the performance of a transportation system, simulations may include extreme thermal conditions such as those in the target region. This testing process helps ensure that the vaccine remains within the required temperature range to ensure efficacy and effectiveness during transport.

These simulations or rigorous testing allow us to identify potential weaknesses and make necessary changes to the transport system, ultimately improving its ability to maintain optimal temperature levels under a variety of challenging conditions. This proactive approach not only mitigates risk, but also highlights our commitment to providing high-quality, reliable transportation services, especially when moving sensitive goods.

 

Data analysis

Once the transport process is complete, temperature data is collected and analyzed. Identify deviations from specified temperature ranges and evaluate their impact on the pharmaceutical product.

Once the transport process is complete, it is important to carefully collect and review temperature data to ensure the integrity and effectiveness of the drug product. This post-transport analysis is an important step in quality control and ensures the effectiveness of sensitive drugs. By identifying deviations from a specified temperature range, the potential effectiveness of pharmaceuticals can be effectively assessed.

Imagine a scenario where a pharmaceutical company is shipping batches of vaccines that require strict temperature control to remain effective. Temperature data loggers installed in shipping containers after the transport phase indicate temporary deviations from the recommended temperature range during that transport leg. This can be caused by unforeseen circumstances, such as border crossing delays or cooling system malfunctions.

By collecting and analyzing this temperature data, companies can determine the exact duration and magnitude of temperature deviations. The potential impact on the safety and efficacy of the vaccine can then be assessed. A drug product may be considered safe for distribution even if the deviations are within acceptable limits and have minimal impact. However, if temperature deviations exceed predetermined thresholds and pose a risk to product quality, appropriate measures, such as product recalls or quality assurance protocols, may need to be implemented.

This comprehensive approach to collecting and analyzing temperature data not only ensures regulatory compliance, but also strengthens our commitment to providing high-quality pharmaceutical products to end users. Demonstrates a proactive approach to maintaining product performance and building trust among both consumers and regulators.

 

Generate report

Generate comprehensive reports detailing temperature mapping results. Provides information on temperature fluctuations, travel duration and corrective actions taken. These reports are essential for compliance and audit purposes.
Generate in-depth, detailed reports that provide detailed analysis of your temperature mapping results. The report should provide a comprehensive overview of observed temperature fluctuations in the monitored environment and include information on the magnitude, frequency, and duration of the deviations. Include a thorough description of the corrective actions taken to address deviations from specified temperature parameters.

These reports play a critical role in ensuring compliance with regulatory standards and serve as important documentation for audit purposes. A real-life example that demonstrates the importance of these reports is a pharmaceutical warehouse. In these environments, it is important to maintain precise temperature conditions to maintain drug efficacy. Temperature mapping reports document storage temperature fluctuations, the duration of conditions that cause deviations from the required range, and the actions taken to correct these deviations. This detailed documentation not only ensures regulatory compliance, but also provides a transparent audit trail and demonstrates commitment to the quality assurance and integrity of stored pharmaceutical products.

 

Continuous improvement

Leverage insights gained from temperature mapping practices to implement continuous improvement actions. This may include adjusting transportation protocols, upgrading equipment, or improving temperature control technology.

By taking these steps, pharmaceutical companies can ensure that their product transportation systems meet temperature requirements, reducing the risk of product spoilage and ensuring the safety and effectiveness of the drugs being transported.

Use the insights gained from your heat mapping exercise to begin a comprehensive, iterative improvement process. This requires a close examination of temperature-sensitive zones along transport routes, paving the way for implementing sophisticated continuous improvement measures. This multifaceted approach may include fine-tuning transport protocols, upgrading equipment to state-of-the-art standards, and improving temperature control technology.

For example, imagine a pharmaceutical company that regularly performs temperature mapping throughout its supply chain. Through these systematic assessments, the company identifies potential weaknesses in the transportation system and identifies areas where temperature fluctuations may occur. With this knowledge, companies can begin to adjust their transportation protocols to meet the stringent temperature requirements during drug handling and storage.

In a real-world scenario, companies may want to invest in state-of-the-art temperature monitoring technology integrated into shipping containers. These devices provide real-time data and allow logistics teams to proactively respond to deviations from optimal temperature ranges during transport. At the same time, companies can strengthen their fleets with refrigerated vehicles equipped with advanced temperature control systems, strengthening the overall integrity of the cold chain.

Continuous improvement measures also include further development of temperature control technology beyond physical changes. This may include implementing more sophisticated predictive analytics algorithms to help companies predict and mitigate potential temperature fluctuations before they occur. These precautions go a long way in reducing the risk of product deterioration during transport.

By carefully following these steps, pharmaceutical companies create robust structures that ensure their product transportation systems can consistently meet stringent temperature requirements. This helps reduce the risk of drug deterioration and maintains the safety, efficacy, and overall quality of the drugs being transported. This commitment to continuous improvement not only secures the company’s reputation, but also emphasizes its commitment to providing end users with high-quality medicines with unwavering reliability.

 

Documentation and Standard Operating Procedures (SOPs)

Develop and implement SOPs for all aspects of the transportation process. This includes loading and unloading operations, handling temperature-sensitive products, equipment maintenance, and emergency protocols. Maintain detailed records of all activities.
Develop and implement comprehensive standard operating procedures (SOPs) that cover all aspects of the transportation process. This includes writing detailed instructions for loading and unloading procedures, ensuring proper handling of temperature-sensitive products, establishing strict equipment maintenance protocols, and implementing clearly defined emergency response procedures. The goal is to streamline and optimize the entire transportation process, promoting efficiency, safety and compliance with industry standards.

For example, for a logistics company specializing in pharmaceutical distribution, SOPs for temperature-sensitive products establish specific protocols for loading and unloading pharmaceutical products to maintain the integrity of the temperature-controlled environment. This may include using special equipment, monitoring temperature conditions during transport, and implementing emergency plans if unexpected temperature deviations occur.

SOPs also include a thorough schedule for equipment maintenance and outline routine inspections and maintenance to prevent breakdowns and ensure the reliability of transportation vehicles. Emergency protocols detail step-by-step procedures for handling unexpected situations, such as accidents, spills, or mechanical failures during transportation, to reduce risk and protect both personnel and cargo.

A robust record-keeping system will be established to document every step of the transport process to improve accountability and traceability. This can include loading and unloading times, temperature records, maintenance activities and any event that triggers an emergency response. These detailed records not only provide a valuable resource for audits and continuous improvement, but also help you comply with regulatory requirements.

Developing and implementing SOPs in the transportation industry involves a multifaceted approach to loading and unloading, handling temperature-sensitive products, maintaining equipment, responding to emergency situations, and maintaining accurate records. This comprehensive strategy ensures operational excellence, promotes a culture of safety and compliance, and provides a solid foundation for continuous improvement of our transportation processes.

 

Qualification of Transportation Partners

If a third-party logistics provider is involved, ensure that they are qualified and meet the required standards for handling pharmaceuticals. This may include facility audits and review of transportation protocols.

When hiring external logistics service providers for pharmaceutical management, it is essential to ensure their competency and compliance with required standards. This includes conducting thorough audits of facilities and reviewing transportation protocols to ensure the integrity and security of the pharmaceutical supply chain.
For example, imagine a pharmaceutical company that relies on an external logistics provider to transport temperature-sensitive vaccines. Companies must ensure that their logistics service providers have the necessary qualifications to handle these sensitive products and comply with industry standards. This includes an inspection of the supplier’s storage facilities to ensure they are equipped with up-to-date temperature control systems and monitoring equipment. Vehicles must also be properly equipped for temperature-controlled transport, and a full review of transport protocols should be undertaken to minimize the risk of temperature fluctuations during travel.

Third-party logistics providers should also be assessed for compliance with their documentation and procedures to ensure they are adhering to best practices and regulatory requirements. This includes accurately recording temperature conditions during transport, implementing strict quality control systems, and having contingency plans in case unexpected problems arise.

By carefully vetting third-party logistics providers, pharmaceutical companies can improve the reliability and compliance of their supply chain and ensure the efficacy and safety of their drugs throughout the distribution chain.

 

Performance Qualifications (PQ)

Carry out transport processes under normal operating conditions by monitoring critical parameters. Ensure that your transport system always meets specified requirements. This may involve providing multiple tests.

We seamlessly manage the transportation process under smooth operating conditions and closely monitor key parameters throughout the journey. The goal is to ensure that the transportation system consistently complies with prescribed requirements. This verification process may require running multiple tests, each of which serves as a real-world example to evaluate the reliability and performance of the system.

For example, managing transportation processes in the context of a global logistics company involves coordinating the movement of goods from manufacturing facilities to distribution centers. During this process, important parameters such as temperature, humidity and operating conditions are continuously monitored. Companies can set specific requirements for each shipment, such as maintaining a specific temperature range for perishable products or handling sensitive items with the utmost care.

To ensure that the transport system complies with these specifications, the company has launched a series of test transports over different routes and under different environmental conditions. These tests serve as real-world examples to evaluate how well a system adapts to different situations and consistently meets specific requirements. The data collected during these tests not only ensures the reliability of the system, but also helps improve and optimize transportation processes for future operations.

 

Data analysis and reporting

During the Transportation System Validation, data collected is analyzed and compared to specified acceptance criteria. Prepare a comprehensive verification report including all relevant information, deviations and corrective actions taken.

During the validation process, data collected is reviewed and compared to predetermined acceptance criteria to ensure compliance and reliability of the process or system being tested. We then prepare a comprehensive verification report that includes a thorough analysis of relevant data, observed deviations from expected values, and appropriate corrective actions to address the deviations.

For example, imagine a pharmaceutical company performing validation of a new manufacturing process. Data collected in these situations may include parameters such as temperature, pressure, and reaction time. These data points are carefully evaluated against predetermined benchmarks to ensure compliance with quality standards. If deviations are identified, the verification report will not only document these deviations but also describe corrective actions, including: B. Recalibration of equipment or process optimization to ensure that the manufacturing process meets established standards. The comprehensive nature of verification reporting is critical to compliance and continuous improvement and provides stakeholders with a transparent and easy-to-understand overview of the verification process.

 

Review and Approval

Ensure Transportation System Validation results and documentation are reviewed by stakeholders, including quality assurance and regulatory personnel. Get approval for valid transportation.
It is important to carefully review the results of the verification and related documentation of your transportation system, including with key stakeholders such as quality assurance and regulatory personnel. This comprehensive review process ensures that your transportation system meets required standards and complies with legal requirements.

For example, when validating temperature-controlled transport systems for sensitive drug delivery in the pharmaceutical industry, it is essential to involve quality assurance experts to evaluate the reliability of temperature monitors, data loggers, and other component critics. Regulators are involved in ensuring compliance with guidance from health authorities, such as the FDA or equivalent regulatory authorities in various regions.

Involving stakeholders in the review process not only improves transparency but also helps identify potential risks and opportunities for improvement. This allows a comprehensive assessment of the feasibility of the transport system, taking into account different perspectives and expertise.

Additionally, obtaining approval for a valid transportation system is a critical step in the entire process. Validated data and documentation are provided to decision makers authorized to approve the system for operational use. In pharmaceutical cases, compliance with Good Distribution Practices (GDP) guidelines may require regulatory approval.

By ensuring thorough audits and obtaining formal approvals from all stakeholders, companies can gain confidence in the reliability and compliance of their transportation systems, reducing risk and ensuring safe and efficient delivery of goods or products.

 

Continuous Monitoring and Revalidation

Implement systems to continuously monitor the transportation process, including regular inspections and periodic reviews of equipment, to ensure ongoing compliance with standards and regulations.

It is essential to establish a robust system to continuously monitor the transport process. This includes regular equipment inspections and regular audit procedures to ensure ongoing compliance with established standards and regulations. This comprehensive approach not only ensures the efficiency of the transport system, but also protects against potential risks and breaches.

To deepen implementation, companies can use advanced monitoring technologies such as IoT-enabled sensors and real-time tracking systems. These tools provide a continuous flow of data and can immediately detect any deviations from prescribed standards. For example, in the maritime sector, installing sensors on containers can monitor environmental conditions in real time and transport goods within specified temperature and humidity limits.

Regular inspection of equipment is essential to maintain optimal operating conditions. Let’s take the aviation industry as an example. Airlines regularly thoroughly inspect aircraft components, from engines to avionics, for signs of wear that could compromise safety or compliance. This proactive approach not only extends the life of your equipment, but also reduces the likelihood of disruption to your transport process.

Regular reviews are also important to ensure continued compliance with evolving standards and regulations. In the automotive industry, car manufacturers frequently update their vehicles to meet new emissions standards and safety regulations. Implementing a system with a planned review process can help ensure your transportation operations meet the latest industry requirements and contribute to long-term sustainability and compliance.

To maintain the integrity of your transportation process, it is important to implement a continuous monitoring system with regular equipment testing and periodic recalibration. Integrating advanced technologies and following industry-specific precedents can increase the efficiency of these systems and ultimately improve the efficiency, safety, and compliance of transportation dynamics.

 

Regulatory Agreement 

Ensure that all Transportation System Validation activities and documentation comply with relevant regulatory requirements, including: b. Good Distribution Practices (GDP) and all other applicable guidelines.

Validation of transport systems is a continuous process and changes to the transport process or equipment trigger revalidation to ensure continued compliance with pharmaceutical quality standards.

It is important to ensure that each verification project and associated documentation carefully complies with the relevant regulatory requirements, especially Good Distribution Practices (GDP) and all other applicable guidance. This ensures that the transport system operates within defined parameters and that pharmaceutical quality standards are met with maximum integrity.

In practice, GDP compliance includes implementing comprehensive protocols and documented procedures to ensure the quality and integrity of pharmaceutical products during transport. For example, maintaining appropriate temperature control, monitoring and recording throughout the transportation process is an important part of the BIP. This includes the use of temperature-controlled vehicles, monitoring devices and data loggers to ensure that medicines are maintained within specified temperature ranges to maintain their effectiveness and safety.

Additionally, compliance efforts extend beyond the initial verification phase. It is essential to recognize the feasibility of transport systems as an ongoing process. Any changes to the transport process or equipment will require revalidation. For example, if transportation is modernized or sales channels change, a comprehensive restructuring process must be initiated. This proactive approach ensures that the delivery system always meets pharmaceutical quality standards and can adapt to any changes or developments in the industry.

To illustrate, imagine a scenario where a pharmaceutical company decides to implement a new tracking and monitoring system for its distribution fleet. In this case, the company should initiate a review process to assess the impact of these technological changes on the transport system’s compliance with GDP and other relevant policies. This comprehensive approach allows the company to stay ahead of regulatory requirements and maintain the highest standards in drug transportation.

In summary, careful attention to regulatory compliance, especially as it relates to GDP, combined with a proactive approach to ongoing verification, is critical to pharmaceutical transport systems. By incorporating these principles into the validation process, companies can safely manage changes in their transportation processes to maintain ongoing pharmaceutical quality standards.

Transportation System Validation for Pharmaceutical Products Read More »

Tablet Manufacturing Process Overview

Tablet manufacturing process, precision is important to ensure the production of high-quality pharmaceuticals or dietary supplements. The first step involves thoroughly mixing the powder, which is a critical step in ensuring the ingredients combine into a homogeneous mixture. Not only must the powder be well mixed, but it must also meet strict standards for uniform size and weight. This allows us to consistently and accurately measure each tablet while maintaining the desired dosage and potency.

After the mixing step, the prepared powder is carefully placed into a die, a special piece of equipment that plays an important role in tablet formation. The matrix acts like a mold, giving the tablet a specific shape and size. This step is essential to achieve a uniform and consistent appearance of the tablets and contributes to both aesthetics and functionality.

Once the powder is firmly seated in the mold, the mold itself is inserted into a punch, another essential part of the tablet manufacturing process. Punches apply pressure to a powder-filled die, compressing the material into the exact shape needed for tableting. This compression process is critical to producing tablets with appropriate hardness, disintegration characteristics, and overall structural integrity.

The newly formed tablets are ejected from the punch, completing the forming process. But the journey doesn’t end here. Tablets undergo extensive testing to ensure quality and compliance with industry standards. This inspection checks various characteristics including size, weight, color, and surface finish. We maintain the highest level of product quality by identifying and correcting any inconsistencies or defects.

Simply put, the tablet manufacturing process is a multi-step process that requires great attention to detail. From powder mixing to molding, punch compression and final inspection, each step plays a critical role in producing tablets that not only look good but also consistently, accurately and reliably deliver the intended dosage. Here is the steps

  • Granulation
  • Blending
  • Compression
  • Tablet Coating
  • Tablet Printing
  • Quality Control
  • Packaging
  • Cleaning
  • Transportation and
  • Storage

 

Granulation:

Granulation is an important manufacturing process that agglomerates fine dust particles to form granules. This conversion step is quite important as it improves the flow properties of the powder and helps achieve a uniform tablet content. The process involves mixing individual powder particles, promoting cohesion, and promoting the formation of granules with desired properties.

Wet granulation and dry granulation are the two main technologies in this process, each offering different benefits and uses. During wet granulation, a liquid binder is added to the powder mixture to promote particle adhesion and subsequent granule formation. This process is particularly effective in producing granules with improved compressibility and flowability.

Dry granulation, on the other hand, does not require the use of liquid and forms granules based on mechanical compression. This method is advantageous when dealing with moisture-sensitive materials or formulations where liquid addition may be problematic. Dry granulation is often chosen for its ability to preserve the integrity of certain active ingredients and is known as granulation efficiency.

In essence, granulation plays an important role in the pharmaceutical industry and other industries as it optimizes the physical properties of the powder, ensures uniform tablet content, and provides the flexibility to choose between wet and dry granulation methods depending on specific formulation requirements. Do it.

In the pharmaceutical industry, tablet granulation is the process of agglomerating fine powders into larger granules to improve the flow and compression properties of the powder, making it suitable for tablet production. There are several tablet granulation methods commonly used by pharmaceutical companies. The main types are:

 

Dry granulation:

Slugging: Involves compressing (slugging) a dry powder mixture into large tablets and then granulating them. This method is suitable for heat-sensitive drugs or drugs that do not compress easily.
Dry granulation, also known as slugging, is a pharmaceutical tablet manufacturing process in which a dry powder mixture is compressed into large, flat tablets, or slugs, which are then granulated. This method is used in cases where the use of a liquid binder or the addition of moisture is not desirable, such as drugs that are sensitive to moisture or drugs that are unstable in the presence of moisture. The dry granulation process generally consists of the following steps:

Mixture of powders:

The first step is to mix the active pharmaceutical ingredient (API) with other excipients such as binders, diluents, and disintegrants to form a homogeneous powder mixture. This mixture is used as the main ingredient in the dry granulation process.

Slugging:

The powder mixture is then compressed into large, flat tablets or blanks using a high-performance tablet press. The compression forces used during agitation are higher than those used in the final compression step of the tablet. The resulting blanks are typically 0.5 to 2 inches in diameter and about 0.1 to 0.5 inches thick.

Milling or Screening:

After grinding, the large lumps are crushed or pulverized into granules. This can be achieved using grinding processes such as vibrating mills, cone mills or screening processes. The objective is to obtain granules of desired particle size for subsequent tablet compression.

Mixed lubrication:

Crushed granules can also be mixed with lubricants to improve flow characteristics and reduce friction during tablet compression. For this purpose, lubricants such as magnesium stearate are commonly used.

The advantages of dry granulation (slugging) are:

Moisture Sensitive Drugs: Suitable for moisture sensitive drugs as there is no need to add water or other liquid binders to the process.

Improved flow properties: The milling step improves the flow properties of the powder mixture and improves compression of the tablets.

Reduces production costs: Dry granulation can be a cost-effective option because it eliminates the drying step associated with wet granulation.

However, it is important to note that not all formulations are suitable for dry granulation and factors such as powder flow, compressibility, and drug type must be considered when selecting an appropriate tablet manufacturing process.

 

Wet Granulation:

High Shear Granulation: The process of adding a liquid binder to a powder mixture and then granulating it using a high shear mixer or granulator. The wet mass is then dried and crushed to obtain beans.
Fluid bed granulation: A fluid bed is used to granulate powder by spraying a binder solution onto the fluidized powder particles.

Wet granulation is a common method of producing tablets in the pharmaceutical industry. It involves wetting the powder mixture with a liquid binder to form granules. This process improves the flow, compressibility and uniformity of the powder mixture, making it suitable for tablet compression. Below is a step-by-step description of the wet granulation process.

Material selection:

The first step involves selecting the active pharmaceutical ingredient (API), excipients, and other ingredients needed for the tablet formulation. These ingredients are usually in powder form.

Weighing and mixing:

Weigh measured amounts of API and excipients and mix thoroughly to obtain a homogeneous powder mixture. This mixture is used as the main ingredient in the granulation process.

Preparation of granulation binder:

It is a liquid binder, often prepared as an aqueous solution or solvent. These binders are used to wet the powder mixture and promote granule formation.

Wet the powder mixture:

Add the liquid binder slowly to the powder mixture while mixing continuously. The goal is to distribute the liquid evenly throughout the powder to properly wet the particles.

Agitation and granulation:

Stir the wet mass to promote the formation of small granules. Liquid binders help bind particles together to create larger, more cohesive particles. This step is important to achieve the desired particle size and improve the flow properties of the material.

Drying:

After milling, the wet beans are dried to remove excess moisture. Drying can be accomplished using various methods such as fluidized bed drying, tray drying or rotary drying. Proper drying is important to prevent tablets from sticking, sealing, or stacking during compression.

Size and screening:

The dried granules can be subjected to further processing, for example sorting and screening, to obtain a uniform particle size. This step will help you determine compatibility of your tablet’s features.

Mixed lubrication:

Lubricants can be added to the granules to improve the compression of the tablets and prevent the tablets from sticking to the tool during the compression process.

Wet granulation is a versatile and widely used method for pharmaceutical tablet production and offers advantages such as improved flow characteristics, compressibility and content uniformity.

Direct compression:

There is no harsh feeling. For some formulations, especially those containing highly compressible excipients and active ingredients, a separate granulation step may not be necessary. The powder is directly compressed into tablets.
Direct compression is a common method of producing tablets in the pharmaceutical industry. In this process, a mixture of active pharmaceutical ingredient (API) and excipients is compressed directly into tablets without an intermediate granulation step. This method is chosen when the flow and compressibility of the formulation components is good.

The following is an overview of the direct compression process for tablet manufacturing process.

Formulation development:

Formulations are designed to contain an active pharmaceutical ingredient (API) and various excipients such as binders, fillers, disintegrants, lubricants, and sometimes flavoring agents.
Excipients are selected based on consistency, fluidity, and compressibility.

Prepare the mixture:

Carefully mix all raw materials, including API and excipients, to obtain a homogeneous mixture. The mixture should have uniform particle size distribution and good flow characteristics.

Tablet compression:

The mixed powder is compressed directly using a tablet press to make tablets.
Tablet presses apply pressure to compress the powder mixture into the desired tablet shape.
The compression force must be carefully controlled to ensure that the tablets have uniform weight, stiffness, and disintegration behavior.

 Tools and Equipment:

Tablet presses are equipped with special equipment to determine the size and shape of tablets.
This tool also serves to control the thickness and hardness of the tablet.

Quality Control:

Quality control measures are implemented in the process to monitor key parameters such as tablet weight, hardness, friability and disintegration time.
Quality control testing helps ensure that each tablet meets required specifications.

Advantages of direct compression:
  • Time and cost efficiency: Direct compression saves time and reduces costs by eliminating intermediate, granular steps.
  • Requires less equipment than other tablet manufacturing process.
  • Because fewer processing steps are required, the risk of poor API performance is reduced.
Challenge

Formulation Challenges: Not all formulations are suitable for direct compression and may require several additional processing steps.
Powder flowability: The powder mixture must have good flow characteristics to ensure consistent tablet weight and strength.

Direct compression is a widely used method in the pharmaceutical industry, especially for formulations where the raw materials have properties favorable to this manufacturing method.

 

Roller compaction:

Dry roller compaction: The powder mixture is compressed between rollers to form a compact film or ribbon, which is then granulated. This method is typically used for materials that are sensitive to moisture or heat.
Roller compaction is a pharmaceutical manufacturing process that converts a fine powder mixture into granules. This process is commonly used in tablet manufacturing process and helps improve the flow properties of the powder and promotes uniform tablet formation. The roller compaction process consists of three main steps: granule feeding, compaction and grinding.

Feeding:

In the first stage, the powder mixture containing the active pharmaceutical ingredient (API), excipients and other essential ingredients is fed into a roller compactor.
The powder mixture is usually poured into a hopper, which feeds the material into the compaction area.

Compaction:

The powder mixture is fed between two counter-rotating rollers.
These rollers apply high pressure to the dust, compressing it. The applied force creates a dense, band-shaped layer of material.
The compressed ribbon passes through a mill where it is reduced to granules of the desired size. The grinding step helps achieve the desired particle size distribution and removes larger particles.

Granule Milling:

The compressed ribbon is passed through a granulator or mill to granulate it.
The granules produced at this stage have improved flow properties compared to the original powder mixture.
The size of the particles is controlled by setting the distance between the rollers and the grinding speed.

The advantages of the roller compression method for tablet manufacturing process include:
Improved flow properties: Roller compaction improves the flowability of the powder mixture, making it easier to handle in subsequent processing steps.
Improved uniformity: The compression process produces more uniform granules, resulting in more uniform tablet weight and drug distribution.

Compression: Roller compaction can increase the density of the powder, improving tablet hardness and strength.
Dust Control: This process helps reduce dust to create a cleaner, safer work environment.

However, it is important to note that the roller compaction method may not be suitable for all types of formulations and that successful tablet production requires careful consideration of the specific properties of the powder mixture.

 

Melt Granulation:

Hot Melt Granulation: Powder particles are held together using a molten binder. The binder is melted, mixed with the powder mixture and cooled to form granules.

Melt granulation is a pharmaceutical tablet manufacturing process in which powdered ingredients are formed into granules using melted or partially melted binders. This process is commonly used to improve the flow, compressibility and dissolution properties of pharmaceutical formulations. Melt granulation technology offers advantages such as improved drug stability, reduced dust generation, and improved content uniformity.

A step-by-step description of the fusion granulation method is given below.

Material selection:

Binder: A binder with a low melting point is selected. Common binders include polyethylene glycol (PEG), glyceryl monostearate, or other similar substances.
API (Active Pharmaceutical Ingredient): A drug formulated into tablets.
Other adjuvants: Depending on the specific requirements of the formulation, additional ingredients such as fillers, disintegrants, and lubricants may be included.

Mixing:

The active ingredients, binders and other excipients are carefully mixed in powder form to ensure a homogeneous mixture.

Granulation:

The mixture is exposed to heat to dissolve the binder. The molten binder wets the powder particles and induces granulation.
Granule size can be controlled by adjusting factors such as binder content, processing temperature, and mixing time.

Cooling:

After granulation, the molten binder is cooled to solidify the granules.

Screening:

The cooled particles are then crushed to obtain a uniform particle size distribution. Granules that are too large or very small can be reprocessed or discarded.

Drying:

If necessary, dry the beans to remove residual moisture and improve stability.

Final mixing:

The granules are mixed with other ingredients not originally included in the melt granulation process. This final mixing ensures uniform distribution of all ingredients.

The melt granulation process is particularly suitable for drugs that are sensitive to moisture or heat. This allows the production of tablets with improved physical properties and dissolution profiles. However, selection of appropriate materials and process parameters is critical to the success of melt granulation technology in pharmaceutical manufacturing.

Spray Drying:

Spray dry granulation:

A liquid binder is sprayed onto powder particles and the mixture is dried in a chamber to form granules.

The choice of granulation method depends on several factors, including the properties of the active ingredients and excipients, the desired properties of the final tablet, and the overall manufacturing process. Each method has advantages and limitations, and pharmaceutical companies can choose the most appropriate method depending on the specific requirements of their formulation.

Spray drying is a commonly used method in the pharmaceutical industry to produce tablets. This process uses a fine spray to convert the liquid feed into dry particles. This process is particularly suitable for heat-sensitive materials and can produce powders with improved solubility, bioavailability and stability. The following is a brief description of the spray drying process for tablet manufacturing.

Liquid formulation:

The process begins with preparing the liquid formulation containing the active pharmaceutical ingredient (API), excipients and other essential ingredients. This liquid may be a solution, suspension, or emulsion.

Atomization:

The liquid formulation is placed in a spray dryer and atomized. Atomization breaks the liquid into smaller droplets, increasing surface area for faster drying.

Drying Chamber:

Atomized water droplets are exposed to a stream of hot air in the drying room. Hot air evaporates the solvent or carrier liquid, leaving behind solid particles. The temperature of the drying room must be carefully controlled to prevent decomposition of the active ingredients or other sensitive ingredients.

Particle collection:

Dry particles are collected by air flow. Collection methods may include cyclonic separators, electrostatic precipitators, or other mechanisms that separate fine particles from the air.

Particle size control:

The particle size of the powder produced through the spray drying process can be controlled. This is important to achieve desired properties such as uniformity and dissolution properties of the final tablet formulation.

Post-drying processing:

After spray drying, the resulting powder may undergo further processing steps such as grinding or sieving to obtain the desired particle size distribution. This step helps ensure consistency in the tablet manufacturing process.

Tablet formulation:

Spray dried powder is used as the active ingredient in tablet formulation. Excipients such as binders, fillers, and disintegrants are added to form a cohesive tablet formulation with the desired release characteristics.

Compression of tablets:

The tablet mixture is compressed into the desired shape using a tablet press. The compression step ensures that the tablets have the correct hardness, thickness, and other physical properties.

The spray drying process is advantageous for pharmaceutical tablet production due to its ability to produce uniform, free-flowing powders with improved bioavailability and stability. It is also suitable for processing heat-sensitive materials that may decompose using other drying methods.

Blending:

The granular material undergoes a carefully calibrated mixing process to obtain a consistent and homogeneous dispersion of both the active pharmaceutical ingredient (API) and the various excipients. This mixing process is essential to ensure complete homogeneity of ingredients, optimizing the overall quality and effectiveness of pharmaceutical formulations. Uniform distribution of active ingredients and excipients not only ensures the stability of the product, but also plays an important role in improving therapeutic efficacy by promoting accurate dosage and absorption of the drug in the human body. These careful mixing procedures are a critical step in the pharmaceutical manufacturing process and contribute significantly to the overall reliability and efficiency of the final drug product.

The compounding process to produce tablets in the pharmaceutical industry involves carefully mixing various pharmaceutical ingredients to form a homogeneous mixture that can be compressed into tablets. The mixing process is a critical step in tablet manufacturing because it ensures that the active pharmaceutical ingredient (API) and excipients are evenly distributed in the final dosage form. Achieving uniformity is important to ensure tablet consistency and performance.

Here you will find an overview of the blending process in tablet production.

Raw material selection:

Pharmaceutical companies select high-quality raw materials based on the suitability of raw materials such as API (active pharmaceutical ingredient) and excipients (inactive substances) and the purpose of the tablet formulation.

Weighing and Dispensing:

Accurate weights and dosages of raw materials are essential to achieve the desired recipe. Accurate measurements help maintain the correct proportions of each ingredient, ensuring consistency in the final product.

Dry mixture:

During dry mixing, the measured ingredients are mixed dry. This can be done using a variety of devices such as drum blenders, V blenders or double cone blenders. The goal is to obtain a homogeneous powder mixture.

Granulation (if required):

In some cases, a granulation step may occur prior to mixing. Granulation involves the formation of granules from powdered materials, which can improve flow properties, compressibility and content uniformity.

Wet mix (if required):

Some formulations may require wet granulation, in which a liquid binder is added to the powder mixture to form granules. Wet mixing can increase the cohesiveness of the mixture and improve the properties of tablets.

Uniformity of the mixture:

After mixing, samples are taken to check the uniformity of the mixture. Samples are analyzed for content uniformity to ensure that the active ingredients are evenly distributed throughout the mixture.

Compression:

The final step is to compress the homogeneous mixture into tablets using a tablet press. When compressed, each tablet contains precise amounts of active and inactive ingredients.

Quality Control:

A strict quality control system is implemented throughout the entire tablet mixing and compression process to monitor and test the quality of the tablets. This includes, among other things, hardness, brittleness, decomposition and dissolution tests.

By taking these steps in the compounding process, pharmaceutical companies can produce tablets that meet the required quality standards, ensuring uniformity and efficiency of the final dosage form.

 

Compression:

The process begins with mixed granules, which are compressed using a tablet press. This critical step in tablet manufacturing requires applying force to the mixed particles to transform the loose particles into a cohesive solid tablet form.

The mixing step serves as an important preliminary step in which the various granular components are carefully mixed until a homogeneous mixture is obtained. This careful mixing process ensures uniform distribution of the active pharmaceutical ingredient and other excipients, contributing to the overall quality and consistency of the final tablet product.

Once the granules are well mixed, the next step is to compress them using a special tablet press. This mechanical device applies controlled pressure to the granules to promote compression of the granules into a defined tablet shape. The compression process not only provides physical integrity to the tablet, but also affects its density, hardness, and dissolution properties.

The tablet press plays a central role in determining the final properties of the tablets as it determines the intensity and duration of pressure applied. These parameters can be adjusted to achieve specific tablet properties depending on the requirements of the pharmaceutical formulation.

Essentially, the compression step is an important aspect of tablet manufacturing because it converts the loose granule mixture into a solid dosage form that is convenient to handle and has desirable therapeutic properties. This systematic approach ensures the production of tablets that meet stringent quality standards and deliver reliable and reproducible results in pharmaceutical applications.

Tablet compression is an important step in the pharmaceutical manufacturing process that converts pharmaceutical powders or granules into compressed tablets. There are several important steps in the compression process.

1. Formulation:

The process begins with the formulation of the tablet where the pharmacist determines the ingredients and their amounts to achieve the desired therapeutic effect. These include active pharmaceutical ingredients (APIs), excipients, binders, lubricants and disintegrants.

2. Granulation:

Raw materials are converted into granules with improved flowability through granulation. Granulation helps produce uniform particle size, reduces dust, and improves compressibility.

3. Tablet press machine:

The tablet press process is mainly performed on tablet press machines. B. There are different types of tablet presses, such as single punch tablet press, rotary tablet press and high-speed tablet press.

4. Die and punch assembly:

The tablet press is equipped with a die and punch assembly. The matrix is the pores that determine the size and shape of the tablet, while the punch is responsible for compressing the granules or powder into tablet form.

5. Loading:

The mixture of granules or powder is loaded into the hopper of the tablet press. The material is then fed into the compaction zone.

6. Compression force:

This is the compression force that combines the upper and lower punches to compress granules or powder into tablets. The compression force must be carefully controlled to ensure that the tablets have the correct hardness and integrity.

7. Discharge:

After compression, the tablets are released from the matrix. The ejection system must be designed to release the tablets without damaging them.

8. Quality Control:

Quality control measures are implemented throughout the compression process to ensure that the tablets meet the required standards. This may include controlling the tablet’s weight, hardness, thickness, friability, and disintegration time.

9. Coating (optional):

Some tablets may undergo a coating process to provide stability, appearance, taste masking, or sustained release.

10. Packaging:

Finally, the compressed tablets are packaged in containers suitable for distribution and use, such as blisters or bottles.

The compression process for tablet production is a highly regulated process in the pharmaceutical industry and compliance with Good Manufacturing Practices (GMP) is essential to ensure safe and effective drug production.

 

 Tablet Coating:

Tablets often undergo a careful coating process to improve not only their attractiveness but also aspects such as taste, stability, and controlled drug release. This critical step in pharmaceutical manufacturing involves several technologies, including film coating and sugar coating, which are emerging as prominent methods. The application of coatings serves a variety of purposes and not only contributes to the aesthetic quality of tablets, but also plays an important role in ensuring optimal drug release, improved palatability and long-term stability. The use of different coating technologies highlights the versatility of pharmaceutical formulations and allows manufacturers to tailor tablet properties to specific therapeutic and patient-based requirements.

Tablet coating is a common pharmaceutical manufacturing process that involves applying a thin layer of coating material to the tablet surface. Coatings are used for a variety of purposes, including improving appearance, masking taste, protecting drugs from environmental influences, controlling drug release, and facilitating swallowing. There are various methods for tablet coating, one of the commonly used methods is film coating. An overview of the tablet coating process is as follows:

Tablet coating process:

1. Preparation of coating liquid:

Coating solutions are prepared by dissolving the coating material (polymer) in a suitable solvent or solvent mixture. The choice of coating material depends on the specific requirements of the tablet and the desired properties of the coating.

2. Charge your tablet:

Tablets are loaded into a coating tray, which is a rotating drum or perforated tray that holds the tablets during the coating process.

3. Spray the coating solution:

Spray the coating solution onto the rolling tablets using a spray system. Spray systems typically consist of a spray gun or nozzle that evenly distributes the coating solution onto the tablets.

4. Drying:

After applying the coating solution, hot air is blown over the tablets as they rotate in the coating tray. This helps evaporate the solvent and leaves a thin, even coating on the tablet.

5. Healing/Curing (optional):

In some cases, a post-curing or drying step may be used to improve the durability and quality of the coating. During this step, the coated tablets are placed in a coating pan under controlled conditions.

6. Inspection and packaging:

Dredges are tested for quality, uniformity and compliance with specifications. Once the coating is satisfactory, the tablets can be packaged.

Factors to consider when coating tablets:

Lining material:

The choice of coating material depends on the specific requirements of the tablet, such as moisture protection, taste masking, or release control.

Coating Thickness:

The thickness of the coating is an important factor and is often controlled to achieve the desired properties without affecting the disintegration or dissolution of the tablet.

Processing conditions:

Factors such as fan speed, inlet air temperature and spray speed are carefully monitored and controlled to ensure uniform coating and efficient drying.

Quality Management:

Regular inspections and quality control tests are carried out to ensure that the dredgers meet the required standards.

The tablet coating process may vary depending on a pharmaceutical company’s specific equipment and technology, but the basic steps remain the same for all methods.

 

 Tablet Printing:

Tablets have the potential to serve as a versatile canvas for disseminating essential product details, company logos or unique identifiers through a variety of advanced printing technologies. These dynamic features not only enhance the aesthetics of the tablet, but also provide an effective means of conveying important information to users and promoting brand awareness and complete identification in a variety of situations. Integrating the printing process into tablets opens up a wide range of customization opportunities and allows manufacturers to print intricate details, promotional materials and branding to create unique and personalized user experiences. Additionally, this innovation adapts to the evolving product presentation landscape, providing a visually appealing platform that goes beyond simple functionality and leaves a lasting impression on customers and stakeholders alike.

Your question seems confusing. Tablet printing is not a standard term in the pharmaceutical manufacturing process. However, I assume you are referring to tablet printing or marking, which is a step in the tablet manufacturing process.

During tablet printing, also known as tablet marking or printing, identifying marks or logos are placed on the tablet surface. This happens for a variety of reasons, including product recognition, branding, and dosage identification. This method uses a tablet printer, also known as a tablet printer.

Below is a general overview of the tablet printing process for pharmaceutical companies.

1. Tablet Production:

Tablets are manufactured mainly through processes such as granulation, tableting, and coating, depending on the dosage form.

2. Tablet printer settings:

The tablet is then sent to a tablet printing machine where the print head is configured according to the desired design, logo or information printed on the tablet.

3. Ink application:

Tablet printers use ink to apply the desired markings to tablets. The ink is generally non-toxic and safe to use.

4. Drying:

After printing, tablets may undergo a drying process to ensure that the ink adheres properly and does not bleed.

5. Inspection:

Printed tablets are inspected to ensure that the markings are clear, accurate and meet legal requirements.

6. Packaging:

Once the inspection passes, the tablets are ready to be packaged. The packaging process involves placing the tablets into blisters, bottles, or other suitable containers.

It is important to note that tablet printing processes in the pharmaceutical industry are highly regulated. Tablet labels often include information such as product name, dosage, and manufacturer logo. The goal is to ensure patient safety through clear and accurate information about medications.

If “tablet printing” means something else, please provide more context so I can give you a more specific answer.

Quality Control:

At every stage of the manufacturing process, a series of careful and extensive quality checks are systematically carried out to ensure that the tablets not only meet established standards but also strictly comply with legal standards. These stringent quality control measures are an essential part of the manufacturing process as they serve to evaluate and verify various characteristics of the tablets, including but not limited to composition, size, and performance characteristics. Performing these checks is essential to maintain the highest level of product integrity and reliability.

From the initial stages of raw material procurement to the final stages of packaging and distribution, each step is carefully considered. The goal is to not only meet industry standards, but also exceed them, ensuring exceptional quality in your tablets. This quality control protocol covers various aspects: B. Chemical composition analysis, physical property evaluation and performance testing. This multi-step approach ensures a holistic evaluation of the purification, taking into account both quantitative and qualitative aspects.

Quality control processes are also designed to promptly identify and resolve any deviations or inconsistencies. Continuous monitoring and documentation are key elements and promote traceability and accountability at all stages of production. This commitment to rigorous quality control practices not only protects the manufacturer’s reputation, but also inspires trust among consumers and regulators.

Additionally, compliance with regulatory standards means more than just compliance. This reflects our commitment to ethical practices and the welfare of our end users. In addition to working to meet the minimum requirements set by regulators, manufacturers are committed to actively keeping up with evolving standards and best practices. This proactive approach will not only ensure that tablets meet current regulatory expectations, but will also position them well for future regulatory developments.

The manufacturing process is characterized by a continuous commitment to quality control, including thorough evaluation of various parameters and a commitment to exceeding industry standards. By adhering to these stringent measures, manufacturers not only ensure that their tablets meet the required specifications, but also maintain their reputation for excellence, reliability, and compliance with regulatory standards.

Quality control is very important in the pharmaceutical industry because it serves as the basis for ensuring the integrity and effectiveness of pharmaceutical products. Each tablet produced undergoes rigorous testing to maintain stringent quality standards. This requires careful monitoring and control throughout the manufacturing process.

Our commitment to quality begins with an extensive series of tests at various stages of tablet production. These tests play a critical role in identifying and resolving potential issues before tablets hit the market, ensuring that only products that meet the highest standards are released for sale.

One of the most complex tests on tablets is the dissolution test. This important evaluation ensures that the tablet dissolves as intended and promotes accurate release of the active ingredients. Accurate resolution is essential as deviations can compromise the intended therapeutic effect and deprive the patient of the effectiveness of the prescribed medication.

Equally important is the content uniformity test, which carefully evaluates the consistency of the active ingredient of all tablets within a batch. This ensures that each tablet contains exactly the same amount of active ingredient. Inconsistencies in content uniformity can have serious consequences, ranging from the risk of overdose to insufficient therapeutic effect, highlighting the importance of maintaining consistency in each tablet.

These careful quality control measures combined ensure that only high-quality tablets are approved for sale. By rigorously testing each tablet, the pharmaceutical industry not only protects the integrity of the product, but more importantly, the well-being of patients. This helps individuals consistently and reliably take the correct medication, adhere to prescribed dosages, and minimize the risk of side effects.

In essence, the pharmaceutical industry’s commitment to quality control is evidence of its commitment to public health and highlights the critical role of rigorous testing protocols in maintaining the highest standards of drug safety, efficacy, and consistency.

Packaging:

After successful completion of quality control procedures, the tablets undergo a packaging process and are placed in final containers, including options such as blisters or bottles. This careful packaging represents the final step before the tablet is ready for distribution to various markets and consumers. Quality control measures ensure that each tablet meets the required standards and that the packaging serves as a protective and practical means for the tablets to be stored, transported and ultimately used by the user. We carefully evaluate your packaging, blister, or bottle selection to ensure compliance with industry regulations, improve product integrity, and ensure easy accessibility. From quality control to packaging, this comprehensive approach demonstrates our commitment to providing trustworthy, high-quality pharmaceutical products to end users.

Tablet packaging and labeling requires careful consideration of many factors that play a critical role in ensuring patient safety and compliance. Initially, the properties of the tablet itself are important, with immediate-release and extended-release tablets emerging as two main categories. Immediate-release tablets are designed to be used as needed, whereas extended-release tablets should be used once daily. This fundamental dichotomy inevitably imposes packaging and labeling requirements and requires different approaches depending on the expected usage patterns.

Upon closer inspection, the dosage of the tablets seems to be another important aspect that requires attention. Tablets are available in a variety of strengths, so it is important that information about the correct dosage is clearly stated on the packaging. Clarity in dosage labeling not only helps healthcare providers determine the correct dosage, but also contributes significantly to patient compliance and understanding.

Additionally, special considerations for specific populations complicate pill packaging and labeling. For example, pediatric patients typically require lower doses than adults. Therefore, packaging and labeling must be tailored to age-specific dosage requirements. Likewise, older patients may have difficulty swallowing tablets and may require alternative formulations such as liquid tablets or crushed tablets. These considerations highlight the importance of adapting packaging strategies to meet the different needs of different patient groups.

In essence, tablet packaging and labeling is more than just a formality. This serves as an important element in the wider context of patient care. The complex interactions between tablet type, dosage, and population require a comprehensive and thoughtful approach. A well-executed strategy not only ensures patient safety, but also improves compliance and promotes a healthcare ecosystem where medicines are accessible, understandable, and tailored to individual needs. Ultimately, the careful design of tablet packaging and labeling forms the basis for achieving optimal treatment outcomes.

Tablet packaging for pharmaceutical companies involves several important steps to ensure the safety, efficacy, and accurate identification of the drug. Below is an overview of a typical tablet packaging process for pharmaceutical companies.

1. Primary packaging:

Blister packaging: Tablets are often packaged in blisters formed by sealing plastic or aluminum foil around individual tablets. Protects your tablet from external factors such as moisture, light, and wind.
Strip packaging: Similar to blister packaging, strip packaging uses tablets shrink-wrapped in plastic or aluminum strips. These strips are then cut into individual doses.

2. Secondary packaging:

Packaging: Once the blisters or blisters are produced, they are packed in boxes. The boxes are intended to provide additional protection and are often labeled with important information such as product name, dosage, lot number, and expiration date.
Packaging: Boxes are placed in larger boxes to provide additional protection during transportation and storage.

3. Labeling:

Labeling: Each individual tablet pack (blister, strip or box) is labeled with important information including product name, active ingredient, dosage, batch number, expiration date, instructions for use and any required warnings.
Serial Number: Many pharmaceutical companies use serial numbers, which assign a unique identifier (serial number) to each package. It helps track products throughout the supply chain to prevent counterfeiting and ensure product integrity.

4. Quality control:

Inspection: Quality control measures are implemented throughout the packaging process to ensure that tablets are properly packaged, labeled and meet required quality standards.
Sampling: Frequent samples are taken from each batch for further testing to ensure the tablets’ quality, stability and compliance with regulatory requirements.

5. Regulatory consent:

Compliance: Pharmaceutical companies must adhere to regulatory guidelines and standards set by health authorities. This includes Good Manufacturing Practice (GMP) regulations that ensure the quality and safety of pharmaceutical products.

6. Tamper-evident packaging:

Tamper-evident seals: For added security, many medications, including tablets, are packaged with tamper-evident seals. These seals are designed to provide visible evidence of tampering and provide an additional level of security to the end user.

7. Supplemental Patient Information:

Patient information leaflet: Some packs contain a patient information leaflet with important information about the medicine, including instructions for use, possible side effects and what to do in case of overdose.

By following these steps and adhering to strict quality control measures, pharmaceutical companies ensure that their tablets are safe and properly packaged for distribution to consumers.

Cleaning:

In tablet production, it is essential to thoroughly clean equipment between production batches. This essential practice serves the dual purpose of preventing cross-contamination and maintaining the highest product quality.

Strict adherence to such practices is not arbitrary. Rather, it is based on good manufacturing practices (GMP) and various other quality regulatory principles. These stringent protocols are carefully followed to ensure the safety, efficacy and overall quality of pharmaceutical tablets. By carefully implementing these guidelines, pharmaceutical companies demonstrate their ongoing commitment to producing tablets that are not only reliable but also consistently meet the highest quality standards.

The importance of these processes cannot be underestimated as they play a key role in reducing risks associated with cross-contamination. If not addressed, this risk could jeopardize the integrity of pharmaceutical tablets and consequently the health and well-being of end users. A commitment to rigorous cleaning protocols therefore forms the basis of quality pharmaceutical manufacturing.

Pharmaceutical companies emphasize the link between these practices and regulatory standards and align their operations with the expectations of health authorities. Complying with GMP and other regulatory parameters is not just a matter of checking a regulatory box. This recognizes the company’s commitment to maintaining the highest standards of quality control.

In essence, thoroughly cleaning equipment is not just a matter of procedure. It is the hub of the entire pharmaceutical manufacturing process. By adopting these practices, companies are embarking on a journey to ensure that every tablet that leaves the factory meets rigorous safety, performance, and quality standards. Our commitment to these principles highlights the important role pharmaceutical manufacturers play in protecting public health by consistently producing high-quality, reliable tablets.

Tablet cleaning is a critical step for pharmaceutical companies to ensure product quality, safety, and compliance with regulatory standards. Cleaning processes are typically performed using proven methods to prevent cross-contamination and maintain the efficiency of the production facility. The following is a general overview of tablet cleaning procedures in pharmaceutical companies.

1. Select equipment:

To reduce the risk of cross-contamination, use specific equipment for each product.
Make sure your cleaning tools are made of materials that are resistant to the detergents used.

2. Preparation:

Clearly define and document cleaning procedures in standard operating procedures (SOPs).
Provide necessary cleaning products and equipment, including cleaning supplies, water, brushes, cloths, and other necessary equipment.

3. Disassembly and disassembly:

Disassemble tablet manufacturing process equipment according to equipment manufacturer’s instructions and cleaning SOPs.
Separable individual parts such as hoppers, feeders and individual cleaning equipment.

4. Dry cleaning:

Use dry methods, such as a brush or vacuum, to remove any visible debris, dirt, or dust.
Avoid compressed air as it can spread contaminants.

5. Wet cleaning:

Prepare a cleaning solution based on the cleaning agent recommended for the specific equipment and residue.
Apply cleaning solution using any appropriate method, such as spraying, wiping, or dipping.
Allow sufficient exposure time to effectively remove residue.

6. Rinsing:

Rinse the device thoroughly with clean water to remove any detergent residue.
To ensure the quality of your wash water, use a proven water treatment system.

7. Drying:

To avoid moisture-related problems, make sure all materials are completely dry.
If necessary, use controlled drying methods such as hot air or inert gas drying.

8. Visual inspection:

Visually inspect all cleaned components to ensure there is no visible residue or contaminants.
Document inspection results.

9. Reassembly:

Reassemble the equipment following the assembly procedures outlined in the SOP.
Make sure the orientation and function are correct.

10. Verification and Documentation:

Test the effectiveness of the cleaning process by cleaning and testing a swab or sample.
Document all cleaning activities, including dates, personnel involved, and inspection results.
Maintain comprehensive compliance records.

11. Validity:

Review your cleaning process regularly to ensure efficiency and reliability.
We update our cleaning procedures based on verification results and continuous improvement plans.

It is important to follow good manufacturing practices (GMP) and regulatory guidance throughout the tablet purification process, such as those provided by organizations such as the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA). Regular training of staff involved in cleaning operations is also essential to maintain consistency and compliance.

 

Transportation 

It is important to ensure the integrity and efficiency of tablets throughout the transport and storage process. These tablets are fragile and must be handled carefully to avoid altering their potency or therapeutic efficacy.

During transport, drug tablets are handled with the utmost care to avoid physical damage. Robust packaging is used to protect the tablets from external forces that could potentially affect the ingredients, and they are usually placed in sturdy containers. Additionally, the tablets are placed on a padded surface inside the package to provide an additional layer of protection.

To further protect the tablets, they are often transported in controlled environments where temperatures are carefully monitored. This method ensures that tablets maintain specified storage conditions and avoids deviations that could affect their chemical stability or therapeutic properties.

Once the tablets arrive at their destination, proper storage is essential to maintain quality. A clean, dry environment free from temperature and humidity extremes is essential. Compliance with these storage conditions is essential to preserve the chemical composition and overall effectiveness of the tablets.

An important aspect of the pharmaceutical industry is the tablet manufacturing process. This complex process plays a critical role in producing tablets that meet stringent quality standards and are safe for human consumption. Understanding the nuances of the tablet manufacturing process can help pharmaceutical companies deliver consistently high-quality products while improving patient care.

The importance of caution also applies to end users. Before consuming any medication, it is important to regularly check the expiration date on the tablet packaging. Expired tablets may undergo chemical changes that may make them ineffective or harmful. This warning emphasizes our commitment to patient safety and the importance of following recommended instructions for storage and use.

In essence, careful handling, transportation and storage of tablets, combined with a comprehensive understanding of the manufacturing process, contribute to the production of safe, effective and high-quality medicines that play an important role in people’s well-being. . patient. health outcomes.

Transportation and storage of tablets are very important steps for pharmaceutical companies to ensure the quality, safety and effectiveness of drugs. These processes must comply with strict guidelines and regulations from health authorities such as the Food and Drug Administration (FDA) or the European Medicines Agency (EMA). Below is an overview of tablet transportation and storage for pharmaceutical companies.

1. Temperature control:

Tablets are sensitive to temperature fluctuations. Pharmaceutical companies use special vehicles equipped with temperature control systems to maintain the necessary storage conditions during transport.
The temperature range for tablet transportation is usually specified on the product label or product instructions. A temperature between 15 and 25 degrees Celsius (59 and 77 degrees Fahrenheit) is recommended.

2. Protect from light and moisture:

Tablets are sensitive to light and moisture, which can affect product quality. Packaging materials must protect against these elements during transport.
To protect the tablets from external environmental influences, packaging that is resistant to light and moisture, such as blisters or opaque containers, can be used.

3. Shock absorption:

Tablets are often packaged in containers with sufficient padding to protect them from impact during transport. This is important to prevent breakage or damage to your tablet.

4. Document:
Accurate and detailed documentation is essential during transport. This includes recording temperature conditions, handling procedures, and deviations from specified conditions.

Storage:

1. Temperature and humidity control:

Pharmaceutical companies store tablets in controlled environments with controlled temperature and humidity. Storage conditions depend on the stability of the drug.
In general, the recommended storage conditions for tablets are room temperature (15-25°C) and low humidity. Some sensitive medications may require refrigerated or frozen storage.

2. Security measures:

Access to storage areas is controlled to prevent access by unauthorized personnel and ensure the safety of medicines.

3. Inventory management:

We have an efficient inventory management system that tracks inventory levels, expiration dates, and tablet movement between storage facilities. This helps prevent the use of expired or damaged products.

4. Good Storage Practices (GSP):

Pharmaceutical companies adhere to best storage practices, including guidelines for cleaning, pest control and organization within storage areas. This ensures that the tablets are stored in a clean and safe environment.

5. Quality Control:

Quality checks are performed regularly to assess the integrity and stability of tablets, which may include sampling and testing according to established protocols.

By following these transportation and storage practices, pharmaceutical companies can ensure that the integrity of their tablets is maintained and that they meet the required quality standards until they reach the end user.

Tablet Manufacturing Process Overview Read More »

What is SOP?

What is SOP? SOP, Standard operating procedures (SOPs) serve as a comprehensive document that represents a structured set of instructions to guide people to perform a specific task or process consistently and accurately. It plays a critical role in a variety of industrial and organizational settings and serves as the foundation for maintaining consistency, efficiency and quality in running operations smoothly.

In the dynamic environments of diverse industries, SOPs represent a strategic tool to streamline processes to ensure a standardized approach. These rigorous and detailed procedures were developed with the primary goal of achieving consistent results. By ensuring a specific sequence of steps, SOPs not only reduce the risk of errors, but also contribute to overall operational efficiency.

One of the main roles of SOPs is to maintain and improve safety standards within an organization. By providing clear guidelines and safety protocols, SOPs help prevent accidents and disasters and create a safe work environment for everyone involved in getting the job done.

Additionally, SOPs are essential to ensure compliance. Industries are governed by a variety of norms, standards and regulations, and SOPs serve as a mechanism to align operations with these obligations. Compliance with these regulatory standards not only helps companies avoid legal consequences, but it also builds trust among stakeholders and demonstrates a commitment to operating a responsible and compliant business.

SOPs also play an important role in employee training and development. These procedures simplify the onboarding process for new employees by providing a standardized roadmap to performance and help them quickly understand how things work. SOPs also provide a valuable reference point for ongoing training plans and ensure employees stay up to date on the latest protocols and best practices.

In essence, the result of an SOP is more than just a procedural document. It embodies our commitment to excellence and guides employees to navigate the complexities of their role, meet safety standards, comply with regulations, and holistically contribute to the overall success of the organization.

 

 

Creating a standard operating procedure: A guide to writing an SOP

Well-developed standard operating procedures (SOPs) act as a comprehensive guide that describes the sequential actions required to complete a task while also informing employees of potential hazards associated with the process. SOP manuals are characterized by being concise and clear, emphasizing not only the “what” but, above all, the “how” of doing something.

It is important to review your SOPs regularly, ideally every 6 to 12 months, to ensure continued relevance and alignment with organizational standards. This requires careful analysis of the procedures, including documented changes to ensure thorough documentation.

Before beginning the SOP design process, a critical step is for authors to perform a comprehensive risk assessment. This assessment includes a detailed examination of each step of the process, with particular attention to identifying potential bottlenecks and associated risks. By proactively identifying problems and threats, SOPs can be tailored to include corrective actions, thereby promoting a proactive approach to performance.

Critical inquiries that ought to be addressed within the standard operating procedure comprise:

When developing standard operating procedures (SOPs), it is important to answer basic questions that include roles and responsibilities within the organization.

1.Identify roles:

– Make it clear who is assigned to each role within the operational framework.
– Define the scope and boundaries of each individual’s responsibilities.

2. Introduction features:

– Describes the specific functions and tasks associated with each assigned role.
– Provides a broad understanding of the behaviors and duties expected of individuals in their respective roles.

3. Definition of results:

– Clearly outline desired goals and outcomes in relation to each individual’s role.
– Establish measurable criteria to evaluate the success and effectiveness of each role.

4. Communication and understanding:

– Evaluate whether the instructions clearly communicate what should happen.
– Make sure everyone involved fully understands their role and the procedures involved.

To determine the adequacy of SOP implementation, companies must conduct a thorough evaluation of their business processes. This is a joint discussion between managers and employees to obtain a detailed overview of day-to-day responsibilities and tasks. In particular, repetitive tasks for multiple employees should be planned for inclusion in SOPs. This systematic approach promotes efficiency and consistency within the organizational structure by documenting and standardizing critical processes.

5. Determine SOP Format

The author must then decide which format to use for the standard operating procedure (SOP). In some cases, companies provide pre-built templates, while in other cases, authors must create their own templates. There are various formats you can consider, including:

Simple steps: Typically presented as bulleted or numbered lists suitable for concise procedures such as security policies. This simple list is ideal for a short, easy-to-understand process.

Sequential Steps: Also consists of bulleted or numbered lists designed for procedures with numerous steps and decisions. This format includes a numbered series of basic steps followed by more detailed substeps.

Once a format is selected, authors must decide whether to distribute the SOP as a physical hard copy or make it available online.

6. Identify task dependencies

In the third step, the author must identify all dependencies associated with the task in question. It is important to identify whether the task depends on other organizational processes. The author must then determine how these dependencies can be incorporated into the new SOP or evaluate whether it would be more appropriate to integrate the new standard operating procedures into existing standard operating procedures.

The writer must then define the target group to appropriately apply the SOP writing style. SOPs for prospective employees differ significantly from SOPs for new hires.

Once these provisions are complete, the writer can begin the SOP writing process. At this stage, it’s a good idea to use present verbs and active voice. The word “you” should be avoided, even if that meaning is acceptable. If your organization provides a style guide, it is important to follow those guidelines.

Elements of SOP:

A well-structured standard operating procedure (SOP) has several essential elements, each of which contributes to transparency, accessibility, and efficiency.

1. Cover page: The SOP should begin with a cover page that includes the title of the procedure, the intended audience (specific role, department, team, or organization), the SOP identification number, and the names and signatures of the people involved. Arrangements and approvals are listed.

2. Table of Contents: In large SOPs, a table of contents is essential to provide quick access to various sections and facilitate navigation.

3. Step-by-step procedures: The core of an SOP is a detailed list of step-by-step procedures. This section should include the scope of work, describe roles and responsibilities, address regulatory requirements, explain relevant terminology, describe actions required for each step, and discuss important decisions. Most of the content of the SOP can be found in this section.

Design and improvement process:

After writing your first draft, thorough reviewing, editing, and testing are essential. This iterative process should continue until the SOP gains approval from all stakeholders. Once approved, the final SOP can be distributed to those who need it in their roles.

The writing process includes:

To ensure completeness, it is important to allow everyone to participate in the review process using SOPs. Your contribution will ensure that all necessary actions are considered and contribute to the effectiveness of the SOP.

SOP best practices:

Adhering to best practices in developing and using SOPs increases organizational efficiency and understanding. The main recommendations are:

1. Consistent style and format: Establish a consistent style and format for all SOPs within your organization. Clear language and defined fonts, spacing, layout, and graphics support employee understanding.

2. Easy content retrieval: Integrate a table of contents into your SOP to simplify access to content. Help your employees quickly find the information they need.

3. Centralized storage: Keep all SOPs in a central location. Keep it online, if possible. This makes it easy to update and change, and ensures your employees can reliably find the information they need.

4. Regular Review and Maintenance: A continuous review and maintenance plan should be implemented to keep SOPs relevant and error-free. SOPs should evolve with the organization and prevent them from becoming obsolete.

5. Distribution and Training Plan: Develop a comprehensive plan to distribute SOPs to employees and conduct training sessions. Regular training beyond training ensures that all employees are up-to-date and understand the latest procedures.

By incorporating these elements and best practices, companies can create SOPs that are comprehensive, easy to use, and adaptable to changing business needs.

Use of standard operating procedures

Standard operating procedures allow companies to better understand their business processes and identify areas that need improvement. Reasons for using SOPs include:

  • A defined program helps maintain fidelity.
  • Employee training support.
  • Ensure compliance standards are met.
  • The certification process has no negative impact on the environment.
  • Ensures the safety of all employees.
  • Avoid potential manufacturing defects.
  • SOPs are still required even if other published procedures are available. The SOP should describe the process in more detail than the published content and explain any differences between the SOP and the published procedure.

If employees do not follow the SOP, the SOP will fail. Management, especially line managers, must monitor the use of standard operating procedures to ensure that they are properly implemented and maintained.

 

Benefits of using standard operating procedures

The two main benefits of using standard operating procedures are consistency and reduced error rates. SOPs can help companies evaluate employee performance, save time and money, and create a safer work environment.

SOPs can also improve communication between organizations. As tasks change, SOPs are updated and distributed to all users, allowing the organization to efficiently communicate changes to all stakeholders. SOPs also reduce the risk of misunderstandings because the detailed steps leave little room for debate or questions.

1. Ensure compliance with best practices and implementation guidelines

Standard operating procedures (SOPs) serve as a framework to ensure strict adherence to industry best practices. What may initially be perceived as simple advice is systematically converted into actionable, hierarchical actions. These practices, designed jointly by stakeholders, ensure that the team always acts in the best interest of the company.

SOPs are not just guiding principles. Provides detailed guidance and acts as a compass for the team. SOPs provide teams with knowledge about the most effective and efficient ways to work, minimizing resource expenditure while delivering optimal results.

2. Establish consistency and efficiency as an organizational model

SOPs serve as an architectural blueprint for organizing your organization like a fine-tuned machine. Create conditions for business continuity and automate decisions and processes to avoid unnecessary considerations and misunderstandings.

3. Improve quality assurance through compliance and consistency

By strictly adhering to best practices and ensuring operational consistency, SOPs play an important role in improving the overall quality of operations. Employees can complete processes or tasks efficiently, raising quality standards.

4. Maintain organizational knowledge for future reference

Although your current team may be familiar with your SOPs, it is important to document them for future reference. Team dynamics inevitably change with retirements, resignations, promotions and job changes. Documented SOPs ensure that accumulated knowledge and skills are maintained within the organization and easily accessible to new members.

5. Optimize onboarding and training processes

Clearly defined standard operating procedures facilitate employee onboarding and improve team training in a variety of scenarios. A well-documented emergency plan will allow your staff to be better prepared to deal with potential problems. Conversely, a lack of detailed steps can leave your team unprepared to handle unknown or unexpected situations.

6. Minimize misunderstandings with detailed instructions

By providing detailed, easily accessible instructions on how to complete a task, SOPs ensure everyone is on the same page, reduce potential misunderstandings, and promote effective communication.

7. Improved safety measures through detailed protocols

SOPs play an important role in reducing the risk of accidents or injuries by outlining safe practices and procedures. For example, SOPs for handling hazardous materials may include steps regarding appropriate protective equipment and handling techniques to ensure safety and risk assessment.

8. Compliance with legal regulations required by law

Some industries require SOP documentation as evidence of compliance with legal requirements. For example, in the healthcare industry, SOP documents often demonstrate compliance with Joint Commission standards. SOPs help businesses meet common legal obligations, including: B. Resolve customer complaints by outlining the steps required to comply with the Terms of Service.

 

Examples of Standard Operating Procedures

  • Examples of how to use SOPs can be found in pharmaceutical production environments. SOPs are used to train workers and record in detail the production line procedures used to produce a product.
  • SOPs can also be used in a financial or management environment to record the processes necessary to accurately invoice and collect payments from customers.
  • A third example of how to use standard operating procedures can be found in customer service, marketing and sales. SOPs can be used to describe service delivery processes and response times, guide the handling of customer complaints and comments, or create sales proposals.
  • Financial organization can also use SOPs to verify the identity of customers who enter them, and the Food and Drug Administration (FDA) can use SOPs to ensure that a company’s operations meet regulatory standards.
  • You can also use standard operating procedures to train employees on collecting, tracking, and storing key performance indicator (KPI) reports, or to create a consistent onboarding experience for new customers.

Finally, SOPs are commonly used in hiring and training employees. In these situations, SOPs can ensure that each individual’s orientation and training is consistent with the experiences of their peers. SOPs can guide managers through day-to-day processes, from disciplinary and corrective actions to performance reviews.

 

How to Write Effective Standard Operating Procedures

Now we’ve covered the basics. You now understand what a Standard Operating Procedure (SOP) is and why it can be a game-changer when it comes to creating and implementing SOPs effectively.

Are you ready for the next step? Let’s take a look at how to write SOPs that your team will actually want to use.

1. Define SOP development goals

Before pen touches paper or fingers touch keyboard, you need to have a clear answer as to why you are writing this document. It’s like preparing for a trip. Before planning your route, you need to know your destination.

Let’s look at some questions to help you formulate your mission.

  • How can SOP documentation increase employee efficiency and teamwork?
  • What does customer service look like when everyone follows SOPs?
  • How will implementing SOPs improve my company’s bottom line?
  • Next, check if there are any issues with your current workflow. This will help you determine exactly how your SOP can help your team become more productive.

Execution Step: Set up a meeting with your team to brainstorm and define SOP goals. Setting smart goals will get you off to a good start!

[Pro tip: Consider using powerful knowledge-based software at this stage and throughout the process, as it can quickly increase your team’s productivity.]

2. End-user identification

Who will be the end users of the SOP? Many people may contribute to the creation of an SOP, but ultimately, specific individuals or departments follow its content.

(For example, if you are creating an SOP to handle customer service requests, the customer service representative will be the primary person responsible for enforcing the SOP.)

Understanding the identity of end users is important to ensure that SOPs can be executed by those performing the defined procedures. Includes:

  • Always focus on the actual responsibilities of the end user.
  • Use language and terminology that resonates with your end users.
  • Clarify relevant terminology that is familiar to end users without providing unnecessary details.
  • Before wrapping up, it’s important to have a clear understanding of who the SOP is intended for in your organization.

3. Identify stakeholders and intermediaries

Building a Dream Team: Given our extensive experience in writing SOPs, it is essential to involve everyone involved or affected by the SOP during development. They must combine a variety of roles to provide expertise.

  • Executive leaders and strategists are responsible for formulating best practices and developing SOP implementation plans.
  • Top executives, thought leaders, are focused on designing efficient operations and achieving overall business goals.
  • As frontline combatants, field personnel are equipped to evaluate the feasibility of SOPs in terms of resourcing and utilization.
  • Practical Steps: Categorize all potential stakeholders involved in your POS and indicate their respective responsibilities.

Don’t overlook the importance of the customer perspective. Although SOPs primarily address internal processes, their results can have a significant impact on the customer experience. Therefore, it is important to keep your audience in mind and create SOPs that not only streamline internal workflows but also improve the overall experience of your customers.

4. Define the scope and format of the SOP

Determining the limitations of the SOP requires consideration of the end users (discussed in the previous step), any equipment or materials required, and any other relevant factors that affect the activities or processes described in the standard operating procedures.

In terms of format, SOPs typically use one of the following structures:

  • Step by Step List
  • hierarchical list
  • flowchart
  • simple checklist
  • video
  • interactive course

Depending on your documentation method, it is important to choose a format that most effectively conveys the desired information. The best approach is to choose the simplest format appropriate for your particular situation. If a step-by-step list is sufficient without further explanation or potential concerns, this may be the most appropriate choice. However, if each step in a process can lead to multiple outcomes, a flowchart may be necessary.

 

Crafting Efficient Standard Operating Procedures

Developing strong standard operating procedures (SOPs) is essential to prioritizing consistency, process streamlining, and safety across various aspects of your company’s operations. The following general guidelines outline the steps necessary to write an effective SOP.

1. State your purpose clearly

Clearly state the purpose of the standard operating procedure (SOP), provide a detailed description of the specific process or task governed by the SOP, and explain its importance. This plays an important role in improving users’ understanding of the contextual relevance and meaning of the methodological framework. By clearly looking at the specific goals and tasks of an SOP, users can better understand procedural complexities and appreciate the broader implications of complying with established policies. This comprehensive explanation not only promotes a deeper understanding of the purpose of SOPs, but also highlights the role of SOPs in ensuring efficiency, consistency, and compliance in an organizational or operational context. In essence, a thorough interpretation of the SOP encourages a broader understanding of the purpose of the SOP and allows for a more informed and diligent approach to SOP implementation.

2. Clearly define the scope

Defining the scope of a standard operating procedure (SOP) requires clearly defining the boundaries of that process. This effectively eliminates potential ambiguity and ensures that the documentation focuses on a well-defined set of activities. These descriptions not only prevent confusion, but also serve as a proactive mechanism to ensure that the SOP focuses only on the specific tasks, procedures, and activities in the area for which it is intended.

Defining the boundaries of the scope of the SOP is important to maintain clarity and consistency in procedural documentation. This process clearly defines the boundaries of the activities covered by the SOP, leaving no room for misunderstanding or uncertainty. As a result, stakeholders, employees, and everyone working with the SOP can confidently navigate the document knowing that the information is specifically related to the intended process.

Additionally, by defining opportunities, organizations can increase the efficiency and effectiveness of their operations. A clearly defined set of activities outlined in an SOP allows for optimized workflows, reduced duplication, and a more targeted approach to resolving operational issues. This ultimately contributes to improving organizational performance and increasing performance consistency.

In essence, carefully delineating the scope of the SOP serves as a strategic strategy to accurately align organizational processes and ensure that the SOP serves as a comprehensive guide tailored to the specific complexities of the intended operation. This strategic clarity not only reduces the risk of system failure, but also lays the foundation for continuous improvement by providing a clear framework for evaluating and optimizing processes over time.

3. Actively involve stakeholders

Participates in collaboration with relevant stakeholders, including those responsible for executing and supervising work. We actively seek input from these stakeholders to ensure the practical relevance of our standard operating procedures (SOPs) and address practical concerns. This improves the effectiveness and practical applicability of SOPs and ultimately enhances their usefulness in everyday situations. This collaborative approach ensures that SOPs not only meet legal requirements but also align with the dynamic needs of the work environment, creating a more complete and adaptable framework for operational success.

4. Adopt a consistent format

Maintain consistent document structure by using a standard format that includes clear, well-defined headings, organized bullet points, and sequentially numbered information. Keeping this structure consistent not only increases the readability of your documentation, but also makes your procedures easier for end users to understand. Clear headings help guide readers through the various sections, while strategic bullet points break complex information into easy-to-understand items. Numbered sequences also help create a logical flow, improving the overall clarity and efficiency of document delivery. This thoughtful approach not only optimizes information, but also promotes a user-friendly experience and ensures procedural details are easy to understand and navigate.

5. Create a clear and concise process

Break the process down into clear, easy-to-understand step-by-step instructions, use simple, clear language, and avoid unnecessary jargon. Describe each step clearly and precisely so there is no room for ambiguity or confusion. By presenting the process clearly, users can follow instructions smoothly and confidently, promoting an easy-to-use and accessible experience. Clarity and accuracy should be emphasized so that each task can be executed smoothly without specific knowledge or skills.

6. Clearly include safety protocols

Safety measures are clearly integrated to ensure seamless integration into the process framework. This includes providing detailed instructions on the use of protective equipment, outlining comprehensive emergency protocols, and considering other relevant safety considerations that arise during the process. Making these safety measures an integral part of the process will not only improve the overall well-being of those involved, but will also help the task at hand be performed more safely and efficiently. Emphasizing and deepening these safety aspects promotes a culture of awareness and responsibility and creates a work environment that minimizes potential risks and equips participants to respond effectively to unexpected situations.

7. Use visuals effectively

Integrate visuals such as flowcharts, diagrams, and illustrations into text content to improve understanding and retention of information. The integration of these complementary elements not only enriches the material but also ensures a diverse learning experience. Visuals serve as powerful tools to clarify complex concepts and add a dynamic, interactive dimension to the information presented. These serve as visual clues that highlight important points and provide a more complete understanding of the topic. Appealing to a variety of learning styles and combining visual and textual content can appeal to a wider audience and promote greater engagement and knowledge retention. In essence, the synergistic integration of text and images transforms static information into more vivid and accessible learning resources, ultimately promoting a deeper understanding of the material.

8. Troubleshooting and FAQs

Anticipate potential problems or requests that may arise during the process. Provide comprehensive troubleshooting information to effectively resolve these issues. We also create a comprehensive set of Frequently Asked Questions (FAQs) to help users overcome potential obstacles they may encounter during the process. This proactive approach aims to improve user experience by resolving concerns early and making the process run more smoothly.

9. Clearly define roles and responsibilities

Carefully outline the specific roles and responsibilities of each person involved in the process. This vigilant organization not only promotes transparency but also acts as a proactive measure to minimize confusion. They also play a critical role in establishing strong accountability structures, thereby increasing the overall effectiveness and efficiency of operations. Clearly defining the roles and responsibilities of each team member creates a structured foundation that fosters smooth collaboration and contributes to successful process execution. This comprehensive approach to role clarification not only streamlines workflow, but also encourages ownership and responsibility among individuals and promotes a culture of accountability and excellence in the organizational environment.

10. Periodic review and revision

We continually evaluate and revise our standard operating procedures (SOPs) to adapt to evolving processes, technological advancements, and government regulations. This proactive approach ensures that SOPs remain current, relevant, and accurate, contributing to the organization’s overall effectiveness, compliance, and adaptability. Regular evaluation of SOPs serves as a strategic measure to capture any changes in workflow, integrate the latest technological innovations, and ensure compliance with the dynamic environment of regulatory standards. By establishing a systematic and regular review process, companies can maintain the integrity of their SOPs, foster a culture of continuous improvement, and ensure that their documented procedures effectively reflect changing aspects of their operating environment. This effort to keep SOPs up-to-date not only increases organizational agility, but also builds trust among stakeholders by demonstrating a commitment to quality and compliance.

11. Ask for feedback

It is important to actively engage with stakeholders and actively seek feedback before reaching the final stage. This iterative approach is critical to uncovering potential problems, filling information gaps, and providing clarity in areas of uncertainty. By actively involving stakeholders throughout the decision-making process, we not only improve the overall quality of our deliverables, but also create a collaborative environment that fosters a comprehensive understanding of the diverse perspectives and insights within a project. By continually seeking input from stakeholders, their valuable expertise can help you identify potential problems, improve decision-making, and ultimately create a stronger, more informed end product or solution.

12. Secure approval and easy delivery

Once you reach the final stage, it is essential to obtain the necessary approvals from both management and relevant authorities. After the approval process, the important next step is to carefully distribute documentation to all affected employees. This distribution should be as complete as possible so that everyone can fully understand the content of the document. This widespread deployment is important for collective awareness and understanding across a team or organization. This not only promotes transparency but also contributes to a consistent and informed approach to the information presented in the documents.

13. Structure of the training session

Provide professional training to ensure people follow standard operating procedures (SOPs). These courses aim to provide a detailed understanding of the methods and promote an understanding of the nuances beyond simple familiarity. As a result, participants acquire the knowledge and skills necessary to implement SOPs correctly and accurately. This targeted training approach ensures that people understand not only the procedural steps but also the underlying principles, promoting the ability to adapt to different situations and make informed decisions according to established protocols. This comprehensive training will provide you with a high level of proficiency that contributes to the overall effectiveness and reliability of SOP compliance in a variety of situations.

14. Research Institute’s Document Management Process

Implementing a strong version control and document management system is critical to maintaining accuracy and consistency across your organization. The system carefully monitors document changes and updates to prevent inconsistencies and ensure users always have access to and reference the most up-to-date and accurate version of the information.

A well-designed version control and document management system not only improves data integrity but also optimizes collaboration among team members. Providing a central repository for documents facilitates efficient sharing, editing, and review processes. This not only reduces the likelihood of errors due to outdated information, but also promotes a smoother, more organized workflow.

Implementing such a system also increases transparency by allowing users to monitor changes in documents over time. Detailed version history and audit trails allow users to see who made specific changes, when they were made, and what the nature of the changes were. This transparency is critical for accountability, quality control, and compliance purposes.

In addition to protecting against inconsistencies, a comprehensive version control and document management system can help increase productivity. Easily finding and accessing the latest versions of documents eliminates confusion caused by outdated information and allows employees to make informed decisions and complete tasks more efficiently.

Additionally, as your business grows, the ability to effectively manage document versions becomes increasingly important. A scalable version control system allows you to accommodate the growing volume and changes to documents within your organization. This scalability ensures that the system remains a stable and integral part of an organization’s infrastructure even as requirements and workflows change.

Simply put, establishing a strong version control and document management system is an investment in accuracy, efficiency, and organizational transparency. This not only prevents inconsistencies, but also allows teams to collaborate effectively, make informed decisions, and adapt to the dynamic nature of business processes.

To understand the importance of a functional Statement of Purpose (SOP), you must understand the dynamic nature of SOPs, which continually adapt to the changing needs of your organization. Because SOPs are living documents, they require regular review and updates to ensure continued validity and effectiveness. Emphasizing the need for regular review and revision is critical to adapting SOPs to an ever-changing organizational environment. This enhances your ability to serve as a strategic guide and significantly contribute to the overall success and adaptability of your organization.

 

Regular reviews of SOPs not only reflect industry trends and commitment to achieving organizational goals, but also demonstrate a proactive approach to maintaining SOPs’ important role in shaping organizational development. This iterative process of evaluation and improvement ensures that the SOP remains a dynamic and responsive tool that can address new challenges and opportunities and ultimately foster the continued success and resilience of the organization.

 

What are the Challenges of Developing a Standard Operating Procedure?

The development of standard operating procedures (SOPs) is important to ensure consistency, efficiency, and compliance of the various processes within an organization. However, there are some challenges associated with writing SOPs. Here are some common challenges:

1. Clarity and Accuracy:

Challenge: The challenge is to ensure clarity, accuracy, and common understanding of the language used in standard operating procedures (SOPs).

Solution: To effectively address this issue, it is essential to adopt a strategy that focuses on using simple and clear language in your SOPs. This method involves incorporating step-by-step instructions while consciously avoiding unnecessary jargon. In this way, we not only improve the overall accessibility of the SOP, but also provide broader understanding to everyone involved in the process.

Audience considerations:

It is important to consider the different audiences your SOP is targeting. Users can include people with varying levels of expertise and familiarity with the topic. Designing a language that is accessible to everyone, regardless of technical background, ensures that your SOP serves as an effective communication tool for everyone involved.

Clarity

Ambiguity in language can lead to misinterpretation and errors when implementing procedures. To mitigate this risk, SOPs should be carefully reviewed to identify and remove any ambiguous terms or unclear instructions. This not only improves the overall quality of your documents, but also contributes to the efficiency and accuracy of the process.

Includes visuals

Supplementing written instructions with visuals such as graphs, diagrams, and illustrations can greatly improve the clarity of your SOPs. Images provide an additional layer of understanding, especially for users who may find concepts easier to understand through images than through text alone.

continuity of terms
It is important to maintain consistency in the terminology used in SOPs to avoid confusion. Creating a standardized vocabulary and applying it consistently to your procedures will help you create a consistent and easily understandable set of documents.

User feedback loop

Establishing a feedback loop with end users can provide valuable insight into the effectiveness of your SOP language. Receiving regular feedback allows for continuous improvement and allows SOPs to evolve based on user experience and level of understanding.

Training and induction programs

Incorporating the clarity of SOP language into your training and onboarding programs will ensure that new team members have the understanding they need from the start. This proactive approach not only accelerates the learning curve, but also lays the foundation for adhering to standardized processes.

In summary, the challenge of ensuring clarity of SOP language is addressed through a holistic approach that includes linguistic simplicity, clarity, visuals, consistent terminology, user feedback, and integration of training programs. This comprehensive strategy promotes an environment in which SOPs serve as effective communication tools for diverse audiences and ultimately contribute to the successful execution of processes within the organization.

2. Scope and scope of application:

The challenge: Finding the right balance between comprehensiveness and simplicity in standard operating procedures (SOPs) by determining the optimal level of detail and scope to comprehensively cover all relevant aspects.

Solution: To overcome this problem, it is important to carefully define the boundaries of the SOP. This avoids the risk of unnecessary complexity and ensures a targeted approach to key processes. Additionally, if an individual requires such granules, it may be useful to consider developing multiple SOPs tailored to specific aspects.

It’s also about navigating the delicate terrain and understanding all relevant aspects without succumbing to information overload. This requires careful consideration of the complex details that contribute to the overall effectiveness of the SOP. Additionally, determining the appropriate level of detail is important to strike a balance between providing comprehensive guidance and avoiding unnecessary conflict.
On the other hand, the proposed solution emphasizes the importance of clarity and precision when defining the boundaries of the SOP. This allows the SOP to maintain a saddle structure that is easily understood without the need for depth. Additionally, the suggestion to consider creating separate SOPs for different aspects emphasizes the adaptability of the approach, allowing for a more appropriate and effective documentation strategy.

Simply put, the challenge is navigating the complexity of detail and scope, and the solution focuses on carefully defining boundaries and creating potentially specialized SOPs. This approach ensures that your POS preserves valuable assets and is accessible to all stakeholders without adding unnecessary complexity.

3. Stay relevant:

Challenge: Adapting standard operating procedures (SOPs) to ensure they remain current and consistent with evolving process, technology, and regulatory environments is a significant organizational challenge.

Solution: To effectively address this issue, it is essential to establish a systematic approach that ensures the ongoing relevance and accuracy of your POS. This includes implementing a systematic and regular review plan and creating a dynamic framework that responds to changes in processes, technology and regulatory requirements.
Expand your solution:

Structured Review Plan

The development of a clearly defined audit plan is the foundation of maintaining SOPs. This timeline should be comprehensive and take into account the nature of the process, the frequency of regulatory changes, and the pace of technological advancement. On a monthly, quarterly, or annual basis, the program should be tailored to the specific needs of your organization.

Assign responsibility

Assign clear responsibility for SOP updates to specific individuals or teams. Assigning ownership ensures accountability and streamlines the process for implementing changes. This may include establishing a dedicated SOP management team that stays abreast of industry updates and proactively implements revisions.

Change Management Protocol

Implement robust change management protocols to ensure process changes are immediately reflected in SOPs. This includes creating ongoing communication channels between the operations team and those responsible for maintaining the SOPs. A transparent process facilitates rapid integration of any changes while ensuring the accuracy and relevance of the process.

Technology integration

Leverage technology to simplify the SOP update process. By implementing a document management system or specialized software that automates version control, you can more easily track changes, identify the latest versions, and distribute updates efficiently. Integrating these technologies can significantly improve the agility of your SOP maintenance process.

Training and awareness programs

Conduct regular training and awareness programs to ensure that all affected employees are aware of the importance of updating SOPs. Training should incorporate the latest changes in processes, technology and regulations and promote a culture of continuous improvement and adaptability within the organization.

Feedback mechanism

Establish a feedback process that encourages employees to provide input about the effectiveness and relevance of SOPs. This can be done through surveys, suggestion boxes, or regular meetings. Including employee feedback ensures that your SOP not only reflects technical accuracy, but also matches the lived experience of the people performing the process.

In summary, a proactive and comprehensive approach to SOP management includes a combination of structured schedules, clear responsibilities, effective change management, technology integration, ongoing training, and feedback loops. By considering these factors, companies can ensure that their SOPs are not only up-to-date but also adaptable to the dynamic nature of their operating environment.

4. User participation:

Challenge: The biggest obstacle is the lack of active participation or valuable input from end users at various stages of the development process.

Solution: A strategic approach to overcome this problem involves active participation and collaboration of stakeholders and end users throughout the standard operating procedures (SOPs) development process. This not only aims to bridge the communication gap, but also strives to create a collaborative environment to gain valuable information and feedback and ensure the practicality and effectiveness of the SOPs developed.

By involving end users in the decision-making and development process, companies can benefit from their unique perspectives and experiences. This inclusion improves the overall quality of the SOP and aligns it more closely with the actual needs, preferences, and expectations of those directly affected by the SOP implementation.

End-user involvement also serves as a proactive measure to identify potential problems and defects early in the development phase. This collaborative approach reduces the risk of overlooking important aspects that may impact the effectiveness of the SOP or user adoption.
To encourage effective participation, organizations can implement a variety of communication channels, including surveys, focus groups, and regular feedback sessions. These platforms allow end users to express concerns, suggest improvements, and share real-world experiences. This iterative feedback loop ensures that the SOP evolves in response to changing circumstances and adapts to the dynamic needs of end users.

Essentially, the solution is to transform the SOP development process into a dynamic, integrated, and iterative journey. By leveraging the collective knowledge of end users and stakeholders, companies can create SOPs that not only meet legal requirements but are also practical, easy to use, and overall efficient.

5. Education and Communication:

Challenge: It is important to ensure that each affected person is thoroughly trained in standard operating procedures (SOPs) and informed of any changes.

Solution: To effectively address this challenge, it is important to develop a well-structured training plan that covers all aspects of the SOP. This plan should include not only initial training, but also regular updates to ensure ongoing competency of relevant staff. Additionally, easily accessible, up-to-date resources contribute to a more efficient training process.

To expand on the concept further, training plans should be tailored to the specific needs and roles of various employees within an organization. Customized training modules can be tailored to meet the individual needs of different departments or teams, facilitating a more targeted and impactful learning experience.

Communication plays a critical role in the success of any training initiative. The solution, therefore, is to implement a strong communication strategy to communicate any changes clearly and in a timely manner to all stakeholders. Using multiple communication channels such as email, meetings, and digital platforms ensures that everyone gets timely information. This approach creates a culture of transparency and accountability within the organization.

To increase the effectiveness of your training program, consider incorporating a system to monitor and document training progress and certification. This not only facilitates compliance monitoring, but is also a useful tool for identifying areas that may require additional attention or clarification. By establishing a systematic monitoring process, organizations can demonstrate their commitment to continuous improvement and SOP compliance.

In summary, the challenge of ensuring all employees are properly trained on SOPs and aware of changes is to develop a comprehensive training plan, provide accessible resources, encourage targeted communication, and effectively manage a robust monitoring system. It will. These diverse solutions foster a culture of continuous learning and compliance within your organization.

6. Resistance to change:

Challenge: Employee resistance to introducing new standard operating procedures (SOPs) is a common obstacle. This is especially true once individuals become accustomed to established practices within the organizational structure.

Solution: Overcoming this problem requires a comprehensive approach that focuses on effective communication, addressing concerns, and actively involving employees in the SOP development process. To successfully manage this transition, it is important to clearly explain and highlight the many benefits that the new SOP brings. By understanding the positive impact on efficiency, productivity, and overall workflow, executives can make a compelling case for adopting change.

Additionally, a key part of the solution is to proactively address any concerns or reservations employees may have about implementing new SOPs. Conducting open forums, town hall meetings, or interactive workshops can provide a platform for employees to express their questions or uncertainties. This not only allows management to clarify misunderstandings, but also fosters a sense of inclusion and shows employees that their perspectives are important in the decision-making process.

Additionally, involving employees in the SOP development process strengthens their personal responsibility and commitment. By gathering opinions, ideas and feedback, executives not only gain valuable insights but also ensure that new approaches are aligned with the actual realities of the workplace. This collaborative approach fosters a culture of continuous improvement and innovation and instills a sense of collective responsibility for the success of the updated SOPs.

To ensure a smooth transition, you need to adapt your communication strategy to the different needs and preferences of your employees. Using a variety of channels, such as newsletters, intranet updates, and interactive training sessions, ensures information is effectively communicated to all employees. By using transparent and accessible communication strategies, organizations can create a supportive environment that encourages change adoption.

In short, addressing employee resistance to new SOPs requires a multi-pronged strategy focused on clear communication, addressing concerns, and active participation. This approach not only increases the likelihood of a successful launch, but also fosters a positive company culture that values adaptability and continuous improvement.

7. Document overload:

Challenge: The current obstacle lies in the overwhelming nature of standard operating procedures (SOPs). This is because standard operating procedures (SOPs) are impractical due to their overly complex details and extensive documentation and pose a serious challenge to users trying to find their way. .

Solution: Overcoming this challenge requires a strategic approach. The key is to prioritize the information needed in the SOP by referencing details and supporting details in separate appendices or documents. We therefore aim to find the right balance between providing comprehensive guidance and ensuring the practicality of using SOPs in real-world situations.

To further develop your solution, it is important to establish a clear hierarchy of information within your SOP. Identify key procedures and policies that are critical to day-to-day operations and place them prominently in the body of the SOP document. This streamlined approach allows users to quickly access basic information without getting bogged down in unnecessary details.

At the same time, additional details, such as specific protocols, technical specifications, or additional background information, may be included in separate appendices or supporting documents. This modular approach not only makes SOPs easier to use, but also allows people to retrieve specific aspects as needed rather than being overwhelmed by a lot of information at once.

Additionally, SOPs require regular review and updates to ensure they meet the organization’s changing needs and remain relevant, constantly assessing the balance between completeness and practicality. You must maintain a dynamic balance between providing comprehensive guidance and maintaining a user-friendly document structure by obtaining regular feedback from end users to identify areas for improvement.

Essentially, the goal is to transform SOPs into valuable resources that promote rather than hinder operational efficiency. By implementing these measures, we aim to create a document framework that serves as a practical and effective guide for users and improves overall efficiency and compliance within your organization.

8. Consistency between SOPs:

Challenge: Standardizing the format, terminology, and structure of all standard operating procedures (SOPs) is a significant barrier to maintaining operational efficiency.

Solution: A strategic approach to fully address this issue includes implementing standardized SOP templates. This model not only enforces consistent formatting, but also enforces consistent terminology throughout the document. Additionally, a clearly defined and standardized framework is established, simplifying content organization and increasing overall transparency.

By adopting this solution, companies can promote ease of use for stakeholders and make SOPs not only easy to navigate but also easy to understand. Standardized templates serve as a framework, increasing consistency in documentation practices and reducing the risk of misunderstandings.

Additionally, this approach provides a more streamlined and collaborative approach to SOP management by allowing teams to seamlessly follow established templates, increasing the efficiency of the creation and update process. Emphasizing consistent terminology can eliminate confusion and promote a common understanding of processes and procedures across different departments and roles.

Ultimately, creating standardized templates coupled with consistent terminology and structure is a critical factor in improving overall efficiency and ensuring that SOPs serve their intended purpose as valuable guidance for employees.

9. Regulatory Agreement:

Challenge: Keeping pace with a dynamic environment of regulatory change is a challenging task and requires constant vigilance to ensure continued compliance with standard operating procedures (SOPs).

Solution: A proactive approach involves appointing a dedicated person or team to carefully monitor and analyze regulatory changes. This certification body must undergo regular and thorough reviews to ensure that the SOPs not only comply with current regulations but are also adaptable to future changes. Implementing these systematic processes ensures that your organization is not only compliant but also prepared for changes in regulatory requirements, promoting regulatory adaptability and a culture of excellence. Regular training for affected employees can further increase awareness and understanding of the evolving regulatory environment and promote a culture of continuous improvement and compliance within the organizational structure.

10. Efficiency Measures:

Challenge: Drive process improvement by evaluating the effectiveness of standard operating procedures (SOPs).

Solution: To effectively measure the impact of SOPs on process improvement, it is essential to establish a comprehensive evaluation framework. This includes defining key performance indicators (KPIs) that serve as quantitative indicators to measure the success and effectiveness of SOP implementation. By developing a solid set of KPIs, companies can gain valuable insight into the effectiveness of their SOPs to streamline operations and achieve desired results.

Regular, systematic evaluations are also essential to maintaining a proactive approach to process improvement. Regular reviews allow companies to examine the intricate details of their processes and identify potential bottlenecks, inefficiencies and opportunities for improvement. This continuous evaluation process not only ensures the continued relevance of the SOPs, but also promotes a culture of continuous improvement within the organization.

To increase the effectiveness of SOPs, organizations should consider incorporating feedback mechanisms and performance indicators into the evaluation process. Obtaining input from relevant stakeholders, including employees directly involved in executing the SOP, generates qualitative insights that complement the quantitative data derived from KPIs. This layered approach allows you to fully understand how your SOPs impact your overall workflow and make targeted improvements as needed.

In addition to assessing the direct impact of SOPs on operational efficiency, organizations should examine the impact of SOPs on broader business goals. Linking SOP effectiveness to strategic goals allows for a holistic assessment that goes beyond immediate process improvements. These strategic alignments allow SOPs to significantly contribute to the overall success of the organization and align operating practices with long-term goals.

In other words, SOPs require a multifaceted and strategic approach to determine their impact on performance and process improvement. By setting effective KPIs, conducting regular evaluations, incorporating stakeholder feedback, and aligning SOPs with business goals, companies can not only quantitatively measure success, but also foster a culture of continuous improvement and adaptability. there is. This comprehensive evaluation process positions the SOP as a dynamic tool that evolves with the needs of the organization, ensuring ongoing operational excellence.

Addressing these challenges requires a thoughtful, collaborative approach that engages key stakeholders throughout the SOP development and implementation process. Regular reviews and updates are important to ensure SOPs remain relevant and effective over time.

 

What happen when a standard operating procedure is not properly implemented?

If standard operating procedures (SOPs) are not implemented properly, they can lead to a variety of negative outcomes that affect both individuals and the organization. The possible results are:

1. Reduced efficiency and productivity:

Failure to adhere to standard operating procedures (SOPs) can have a negative impact on organizational effectiveness. When employees deviate from established SOPs, you run the risk of inefficient processes and disrupted workflows. These deviations can result in valuable time being spent dealing with uncertainty and understanding the processes involved, which ultimately impacts productivity.

Additionally, failure to strictly adhere to SOPs increases the likelihood of performance errors. Employees may accidentally skip important steps or misinterpret procedures, resulting in errors that need to be corrected later. These errors not only consume additional resources but also affect the overall quality of work. These reductions can potentially have far-reaching consequences, including impacting customer satisfaction, damaging your company’s reputation, and affecting your ability to meet deadlines.

Failure to comply with SOPs goes beyond simple procedural errors. This represents a threat to the smooth functioning of the organization. The cumulative effect of inefficient processes, wasted time, and error-related risks can significantly reduce overall productivity. Therefore, ongoing efforts to comply with SOPs are essential to maintaining an optimized and high-performing work environment.

2. Quality problems:

Improper adherence to standard operating procedures (SOPs) can lead to errors and deviations from established benchmarks. These failures can have far-reaching consequences and can lead to poor product or service development. This goes beyond simple quality issues and affects many aspects of operational efficiency and customer satisfaction.

Failure to follow SOPs carefully increases the likelihood of errors occurring at various stages of the process. This lack of precision can compromise the integrity of your overall workflow and cause a variety of issues that impact your bottom line. From manufacturing defects to service delivery defects, the range of potential problems is wide and can impact a wide range of industries.
Moreover, deviations from SOPs can prevent harmonious coordination of established protocols and policies. This not only jeopardizes consistency of results, but can also lead to inefficiencies and delays in production or service delivery. The impact of these deviations can ripple throughout the supply chain, affecting not only immediate results, but also the company’s reputation and credibility.

Improper implementation of SOPs creates multifaceted risks that go beyond quality control. It has the ability to influence overall performance, customer perception, and market competitiveness. Therefore, ongoing efforts to comply with SOPs are critical to ensuring not only the quality of the end result, but also the company’s sustainable success and reputation in a dynamic and highly competitive business environment.

3. Security risks:

Standard operating procedures (SOPs) play an important role in ensuring safety standards in a variety of operating environments. These carefully crafted protocols serve as a comprehensive framework to minimize potential risks and protect the well-being of those involved. Failure to follow these protocols not only jeopardizes worker safety, but also increases the likelihood of accidents, injuries, and exposure to hazardous conditions.

Basically, SOPs serve as an important line of defense against the unpredictability of various work environments. Following these guidelines can help companies create a culture of security awareness and improve overall operational resilience. Ignoring SOPs has consequences that go beyond the immediate risks, as they can have long-term effects on individuals and the organization as a whole.

Failure to strictly follow SOPs increases the risk of accidents and creates many avoidable hazards. Consequences can range from minor accidents to serious injuries, highlighting the importance of these protocols. Additionally, failure to follow standard operating procedures can expose individuals to hazardous situations, putting them at risk for health problems and long-term effects.

Carefully developing and implementing SOPs demonstrates a commitment to a safe work environment. Organizations that prioritize these protocols not only protect their employees, but also strengthen their reputation for responsible and ethical behavior. Ultimately, investing in SOP compliance is about more than just compliance. Promoting a culture of safety, well-being and operational excellence has become a strategic imperative.

4. Compliance and regulatory issues:

Many industries have stringent regulations and compliance standards that require strict adherence to specific procedures. Failure to comply with these standard operating procedures (SOPs) can have far-reaching consequences, potentially exposing your company to legal penalties, financial penalties, and various regulatory actions.

In today’s complex business environment, applying industry-specific procedures is not only a best practice, but a legal requirement. These rules are intended to ensure integrity, safety and ethical conduct in all sectors. Organizations operating within this structure must prioritize carefully implementing SOPs to ensure full compliance with applicable laws and industry standards.

Non-compliance has consequences that go beyond financial penalties. This can damage the company’s reputation and erode stakeholder trust. Regulators have the power to take decisive action against companies that violate established protocols, in line with their mandate to protect the public interest.

In addition to legal penalties and fines, non-compliance may result in increased scrutiny from regulators, including increased reporting requirements, on-site inspections, and imposition of corrective actions. The ripple effect can have a knock-on effect across the entire supply chain, affecting not only the company in question, but also its partners, suppliers and customers.

Additionally, as industries become more globally interconnected, compliance with international standards becomes increasingly important. Companies operating on a multinational scale must navigate a complex web of regulations, with potential consequences for non-compliance both within their own countries and across borders.

To mitigate these risks, companies must establish a robust compliance management system, regularly update SOPs to keep up with evolving regulations, and conduct extensive employee training programs. A proactive compliance approach not only protects against legal consequences, but also promotes a culture of accountability and ethical behavior within your organization.

Compliance with regulatory and compliance requirements, especially through careful adherence to SOPs, is critical to a company’s long-term success and reputation. Recognizing and embracing these obligations can help companies navigate a complex regulatory environment by not only ensuring compliance, but also building a culture of accountability and trust within their industry.

5. Financial results:

Operational inefficiencies, quality control deficiencies and safety incidents within a company can have a serious impact on a company’s financial health. These impacts can be felt through a variety of channels, resulting in increased operating costs, increased corrective action costs, and potential revenue loss.

When companies face inefficiencies, resources are misallocated or underutilized, increasing operating costs. This mismanagement can take many forms, including increased labor costs, wasted materials, and increased production times. The ripple effect of inefficiencies can permeate the entire operating ecosystem and strain an organization’s financial resources.

Quality issues further exacerbate these financial problems. If a product or service does not meet expected standards, corrective action is essential. These corrective actions, ranging from recalls, rework, and warranty claims, inevitably result in additional costs for the company. Additionally, reputational damage due to poor quality can lead to decreased customer loyalty and trust, which can lead to long-term loss of sales.

Safety incidents that occur in a corporate environment not only threaten the well-being of employees, but also have serious financial implications. The costs associated with dealing with workplace accidents and injuries, as well as the potential legal consequences, can add up quickly. Insurance premiums can soar and legal costs increase as businesses struggle to address the fallout from safety issues. Beyond the immediate financial loss, lack of security can discourage potential investors and customers and have a lasting impact on a company’s revenue stream.

The interplay between inefficiencies, quality issues, and security incidents reveals a complex web that has a financial impact on businesses. Recognizing and proactively addressing these issues is important to maintaining a solid financial footing and achieving continued success in a competitive marketplace.

6. Defamation:

A company’s reputation is very vulnerable if it is negatively affected by inconsistent or substandard products and services. If a company fails to maintain consistent quality standards, it risks jeopardizing its market position and damaging its reputation. The impact goes beyond simple financial loss, as negative publicity resulting from security incidents or regulatory violations can have a serious impact on customer trust and loyalty.

In a highly competitive business environment where consumers have many choices, a company’s reputation is an important asset. Inconsistencies or deficiencies in the products and services a company provides can lead to a loss of credibility and make it difficult to retain existing customers and attract new customers. This loss of trust can lead to larger negative stories and affect the overall perception of your brand in the public eye.

Security incidents are an especially important issue because they not only pose a direct threat to consumers, but also require close scrutiny by regulators and the media. If a company is implicated in a security flaw, it not only faces potential legal consequences, but also reputational damage that may be difficult to recover from. Customers are likely to perceive the company as untrustworthy and question its commitment to their well-being, further eroding trust.

Likewise, non-compliance can have serious consequences, including fines, legal action, and the imposition of corrective actions. In addition to the immediate financial impact, the negative publicity associated with regulatory violations can tarnish your brand image and leave a lasting impression on consumers. Loss of trust due to regulatory issues can reduce customer loyalty as consumers may seek alternatives to companies that are perceived as more trustworthy and loyal.

The impact of inconsistent or low-quality products and services goes beyond the immediate financial impact. This extends to reputation management, where customer trust and loyalty are important. Protecting your company’s reputation requires a commitment to maintaining high quality standards, ensuring regulatory compliance, and proactively resolving any issues that may arise.

7. Employee morale and job satisfaction:

Employees can become frustrated and demotivated when they realize that standard operating procedures (SOPs) are not being implemented effectively. This dissatisfaction can have a significant impact on workplace morale and job satisfaction, reducing overall productivity and creating a ripple effect that hinders the achievement of organizational goals.
The implementation of SOPs is crucial for maintaining operational efficiency, ensuring consistency, and upholding quality standards. When employees sense a lack of adherence to these procedures, it can lead to a breakdown in trust and confidence in the organization’s ability to operate smoothly. This breakdown, in turn, fosters a sense of frustration as employees grapple with the challenges and uncertainties arising from inconsistent processes.

The consequences go beyond mere frustration and impact overall employee motivation. Frustrated employees are less willing to actively participate in their work, which reduces productivity and innovation. Job satisfaction, the foundation of employee well-being, is at risk as individuals feel unsupported and undervalued due to the inefficiencies of following procedures.

Moreover, the negative impact of ineffective SOP implementation can create a toxic work environment where interpersonal relationships may suffer and collaboration may be inhibited. As employees seek an environment where their efforts are recognized and processes are more reliably managed, frustration can manifest itself in increased absenteeism, decreased employee engagement, and increased likelihood of turnover.

To address these issues, organizations should prioritize transparent communication about SOPs and provide training and resources to ensure understanding and compliance. A regular evaluation and update process can help address emerging issues and contribute to a culture of continuous improvement. By creating a work environment where employees value their contributions and follow processes consistently, companies can proactively mitigate the negative impacts of ineffective SOP implementation and ultimately create a more positive and productive work environment.

8. Ineffective decision making:

Standard operating procedures (SOPs) play an important role in providing a structured framework to guide decision-making. These carefully written protocols are intended to provide guidance and ensure that those involved in the decision-making process have a clear, structured roadmap. The importance of following SOPs cannot be underestimated. This is because deviations from these established procedures can lead to decisions that are not only ill-informed but also potentially suboptimal or harmful in the long run. Failure to adhere to SOPs can have a domino effect, triggering a chain of events that can have far-reaching, long-term consequences, impacting multiple aspects of an organization or system.

By design, SOPs summarize collective knowledge, best practices, and lessons learned over time. It serves as a repository of institutional knowledge and provides a standardized approach to decision-making that is improved through experience and expertise. Adhering to SOPs is important for making decisions based on unified principles and increasing trust and reliability in the results.

If individuals do not adhere to SOPs, the risk of making decisions in an information vacuum increases significantly. This can lead to a lack of understanding of the wider context, potential risks, and implications of decisions. In essence, failure to adhere to SOPs can lead to decisions that are not only short-sighted, but also ignore important factors that can be addressed through prescribed procedures.

The impact of SOP deviations often extend beyond the immediate results and impact the culture and technical structure of the organization. The erosion of established protocols can create an environment of unpredictability and undermine trust in the decision-making process. Additionally, the long-term impact of poor decisions resulting from non-compliance with SOPs can manifest in poor business performance, reputational damage, and financial implications.
SOPs serve as an essential decision aid and provide a structured approach based on experience and best practices. Failure to follow these procedures not only risks making hasty and uninformed decisions, but also exposes your organization to a series of long-term consequences that can be detrimental to its overall health and performance. Therefore, adhering to SOPs is not simply a matter of compliance, but a strategic imperative for organizations seeking to master the complexities of decision-making through vigilance and foresight.

9. Difficulties with continuous improvement:

Effective implementation of standard operating procedures (SOPs) creates a solid framework for continuous improvement within an organization. The importance of SOP compliance is clearly understood in terms of seamlessly identifying potential areas of improvement and effectively implementing innovative changes.

Without strict adherence to SOPs, companies face serious obstacles to identifying improvement opportunities and successfully implementing change. This not only hinders progress but also reduces the overall effectiveness and efficiency of organizational processes.

It is important for organizations to take a comprehensive approach to address and mitigate these inherent risks. Above all, SOPs must be carefully written and communicated at all levels of the organization, ensuring a clear understanding of procedures and policies, and promoting a culture of compliance and accountability.

It is also important to regularly review and update SOPs to keep pace with industry dynamics and evolving best practices. This iterative process ensures that SOPs remain relevant and consistent with organizational goals and legal requirements. These reviews also provide an important mechanism for identifying gaps or inefficiencies in existing processes.

Employee training is an essential part of SOP implementation. Companies must invest in robust training programs to ensure employees have the skills and knowledge necessary to comply with established SOPs. This not only improves overall efficiency, but also gives employees a sense of responsibility and ownership for the importance of following SOPs.

In addition to clear communication and ongoing training, organizations must establish mechanisms to continuously monitor and enforce SOPs. This includes using systems to monitor compliance, conducting regular audits and taking corrective action when non-compliance is identified. These proactive actions contribute to a culture of discipline and accountability and create an environment where SOPs are viewed as essential to operational success.
A multi-pronged approach to SOP implementation includes clear communication, periodic reviews, in-depth training, and careful monitoring. By incorporating these elements into their organizational structure, companies can not only ensure compliance with SOPs, but also realize their full potential as a catalyst for continuous improvement and sustainable success.

How do you implement new SOPs in your organization?

Implementing new standard operating procedures (SOPs) in your organization requires careful planning, communication, and execution. Below is a step-by-step guide to help you through the process.

1. Identify the need for new SOPs.

It provides an in-depth explanation of the purpose and specific goals underlying the formulation of new standard operating procedures (SOPs). This includes providing a complete and clear description of the SOP’s intended function, goals, and desired outcomes.

Additionally, carefully determine the exact processes or areas within your organizational structure where SOP implementation is deemed essential. Describe the rationale for each area identified and explain how SOPs can help streamline operations, increase efficiency, or ensure compliance with established standards and regulations.

Conduct a comprehensive assessment to evaluate the potential impact of new SOPs on existing workflows and activities within your organization. Examine how introducing an SOP may impact existing processes, roles, or responsibilities and analyze both the positive aspects and potential challenges associated with this change. Consider the impact on various stakeholders, including employees, departments, and external partners.

Expanding on the concept, we describe the expected benefits of implementing the following SOPs: B. Greater accountability, greater quality control, and greater overall organizational effectiveness. At the same time, conduct a thorough risk analysis and propose corrective strategies to address any concerns or risks associated with your SOPs.

By carefully addressing all aspects of goal setting, identifying relevant areas, and assessing impact, companies can gain a broad understanding of the requirements and impact of new SOPs across their entire operating environment.

2. Define scope and goals

Describes the parameters of the standard operating procedure (SOP) in depth and provides a full overview of the scope, clearly identifying areas covered and excluded by the SOP. Clearly indicate the boundaries and limitations of the SOP to ensure an accurate understanding of the intended scope. It also formalizes well-defined, measurable goals that the SOP seeks to achieve, highlighting the specific results and criteria expected from implementation. By clarifying inclusions and exclusions and setting specific, measurable goals, SOPs achieve clarity and efficiency and promote a stronger operational leadership structure. This thoughtful approach not only improves transparency but also promotes a thorough understanding of the purpose and intended impact of the SOP.

3. Write a draft

Write a preliminary version of your Statement of Purpose (SOP), paying particular attention to clarity, conciseness, and overall understandability. Use a standard structure with clearly defined headings, subheadings, and a comprehensive table of contents. Detailed step-by-step instructions are provided to guide readers smoothly through the SOP. Clearly outline the specific responsibilities associated with each department and ensure that the SOP includes all forms or templates needed for effective implementation. This comprehensive approach aims to improve the accessibility of SOPs and promote transparent, user-friendly documentation that facilitates understanding and implementation by various stakeholders.

4. Get comments and feedback

Distribute an initial version of the Standard Operating Procedures (SOPs) to key stakeholders and ensure they are communicated to decision-makers as well as employees directly affected by SOP implementation. Create an inclusive environment for collaboration and contribution by actively seeking feedback from all stakeholders, with particular interest in the day-to-day operations affected by the SOP.

Encourage open communication channels to gather diverse perspectives while addressing potential problems as well as welcoming constructive suggestions for improvement. Emphasizes the importance of collaboration and effort to improve SOPs to better fit operational realities and staffing requirements.

Create mechanisms for stakeholders to express their thoughts, concerns, and ideas through various channels such as feedback sessions, surveys, or specific touchpoints. Ensure a transparent and responsive feedback loop and demonstrate a commitment to incorporating important information into the final version of the SOP.

By actively involving key stakeholders and employees in the review process, we aim to foster a sense of ownership and understanding, and create a culture of collaboration that contributes to the development of more effective and comprehensive standard operating procedures.

5. Review and Edit

We conduct a comprehensive review of the original draft, carefully evaluating its alignment with the organization’s overall goals and ensuring compliance with all applicable legal and regulatory requirements. Then, carefully review your standard operating procedures (SOPs) based on the information and feedback you received during the review process. This includes a detailed analysis of the content, structure and language of the document to ensure that it not only meets established organizational objectives but also complies with all applicable legal frameworks and regulatory standards. Pay particular attention to ensuring the clarity, accuracy, and completeness of SOPs and incorporate modifications where necessary to improve the effectiveness of SOPs and ensure they meet the broader goals of the organization. We also seek input from relevant stakeholders to capture diverse perspectives and ensure a comprehensive and integrated review process. This thoughtful approach to reviewing and revising SOPs is essential to maintaining organizational compliance and optimizing operational efficiency.

6. Approval process

Obtain necessary approvals from relevant departments, managers and other relevant authorities to ensure compliance with legal requirements and organizational protocols. Obtain thorough documentation approvals and maintain accurate records for future reference and audit purposes. This comprehensive approach not only promotes optimized communication and coordination, but also creates transparent and accountable structures within the organizational structure. By systematically documenting approvals, organizations can increase efficiency, reduce potential bottlenecks, and maintain a culture of accountability and compliance. These records provide a valuable resource for future decisions, provide insight into the history and context of approvals, and ultimately contribute to a more informed and agile operating environment.

7. Training and Communication

It is important to develop a comprehensive training strategy to ensure employees fully understand recently introduced standard operating procedures (SOPs). This involves developing a structured instructional plan that includes a variety of methods to accommodate different learning preferences and styles.

To kick off this initiative, organize interactive training sessions so that employees can actively interact with the new SOP concepts. These sessions can be led by knowledgeable instructors or subject matter experts who can answer questions and provide practical insight. Additionally, conduct workshops that promote hands-on learning and allow participants to apply theoretical knowledge in simulated situations to strengthen their understanding.

Create live sessions and comprehensive training materials that are valuable resources for your employees. These materials should address the complexities of the SOP and include visuals, case studies, and real-world examples to aid understanding. Distribute these materials in electronic or paper format and make them accessible to all team members.

Communication plays a critical role in successfully implementing SOPs. Therefore, develop a solid communication plan to disseminate information to all stakeholders. Communicate the details and meaning of the SOP using a variety of channels, including team meetings, email communications, and intranet platforms. Emphasize the importance of loyalty and compliance and how this aligns with the organization’s goals and values.

Additionally, consider implementing a feedback process to measure the effectiveness of your training initiatives. This may include surveys, focus groups or one-to-one feedback sessions to identify areas that may need further clarification or reinforcement. Continuous improvement is key and the feedback received can lead to adjustments to your training plan to achieve optimal results.

In other words, creating a comprehensive training plan requires a multifaceted approach that combines interactive sessions, hands-on workshops, and well-crafted training materials. Effective communication with all stakeholders is essential to reinforce the importance of SOPs and provide clear guidance for successful implementation. Regular feedback mechanisms contribute to the continuous development of the training strategy, ensuring continuous improvement and sustainable uptake of staff.

8. Implementation Plan

If necessary, develop a comprehensive phased implementation strategy and outline a structured plan for phased implementation of the project. We describe each step and provide detailed steps and milestones to ensure an orderly and efficient implementation process. Establish clear, specific roles and responsibilities for all team members involved in the implementation phase and emphasize the importance of each individual’s contribution to the overall success of the project. Clearly define tasks and expectations for each role to increase accountability and optimize communication. This proactive approach to role definition expedites execution, reduces confusion, and improves overall coordination of efforts during the implementation phase.

9. Monitoring and enforcement

Implementing a robust monitoring system is essential to ensure compliance with recently introduced standard operating procedures (SOPs). This monitoring mechanism should be designed to carefully monitor and evaluate compliance with new SOPs and leave no room for ambiguity or regulation. By establishing a comprehensive monitoring framework, organizations can identify and effectively address deviations from established procedures.

Communication plays a critical role in enforcing compliance, and it is important to clearly communicate the consequences associated with non-compliance. The goal is to communicate results in a transparent way for everyone involved. By building a culture of responsibility and awareness, companies can encourage a more disciplined and standardized approach to operations by instilling a sense of responsibility in their employees.

SOPs should also be viewed not as static documents, but as dynamic frameworks that evolve as the organization’s needs change. Regular reviews are essential to evaluate the effectiveness of SOPs and identify areas that may require change or improvement. Regular updates ensure your procedures comply with industry best practices, regulatory requirements, and your organization’s evolving goals and objectives.

In summary, establishing a vigilant monitoring system with clear communication of results and periodic review of SOPs represents a comprehensive strategy for maintaining compliance and promoting a culture of continuous improvement within the organization. This approach not only mitigates the risks associated with regulatory violations, but also improves adaptability and responsiveness in a dynamic business environment.

10. Documentation and Records

Ensure thorough documentation throughout the standard operating procedures (SOPs) development and implementation process. It is important to carefully record each step of the SOP from its initial concept to its final implementation. This document should include all relevant details, including the reasons for specific decisions, key stakeholders involved, and any issues encountered during the development and implementation phases.

We will also establish a complete archive system for all previous versions of the SOP. Keep these versions organized for easy retrieval and reference. In addition to maintaining the latest iteration, it is important to maintain a revision history. This historical log should document the evolution of the SOP and detail any changes, updates, or modifications made over time.

The purposes of this detailed document are manifold. First, it serves as a transparent and accountable representation of SOP development and provides information on the decision-making process and context for future evaluation. Second, the archive of previous versions can be used as a valuable resource for benchmarking, providing a deeper understanding of the progress of the SOP and lessons learned from previous iterations. Finally, a strong audit trail ensures compliance with regulatory requirements and quality assurance standards and enables a proactive approach to continuous improvement of SOP management. By following this comprehensive documentation and archiving strategy, companies can enhance accountability, streamline future updates, and foster a culture of excellence in standard operating procedures.

11. Continuous improvement

We encourage an open and collaborative feedback culture among our users and actively seek feedback to identify specific areas for improvement. By encouraging a continuous cycle of communication, we aim to gain valuable input from our user community and utilize their experiences and perspectives as an important resource to refine and improve our operations.

Comprehensive and regular review of our standard operating procedures (SOPs) is a cornerstone of our pursuit of excellence. These systematic reviews serve the dual purpose of not only identifying potential areas for improvement, but also ensuring that SOPs are not only up to date but optimized for maximum effectiveness.

Through a thoughtful and proactive approach, we are committed to staying abreast of industry trends, technological advancements, and evolving best practices. This commitment to being at the forefront of our field ensures that our SOPs remain a dynamic and responsive framework that can adapt to the ever-changing business environment.

Integrating user feedback with periodic SOP reviews creates a symbiotic relationship where information collected from users informs iterative improvements to the process. This cyclical process allows us to build a culture of continuous improvement where every interaction and evaluation acts as a catalyst for positive change.

Simply put, encouraging user feedback and regularly reviewing and updating SOPs are essential parts of an overall strategy to do more than simply meet expectations. This holistic view allows us to not only identify opportunities for improvement, but also proactively shape our operating structure to ensure we are agile, responsive, and consistently deliver excellence in all aspects of our efforts.

12. Audits and Inspections

We conduct regular comprehensive audits to ensure and maintain compliance with established policies and regulations. Quickly resolve any discrepancies or concerns that arise during these audits to maintain a smooth operating structure. It is important to recognize that successful implementation of standard operating procedures (SOPs) depends on effective communication, active involvement of key stakeholders, and ongoing commitment to continuous improvement.

To facilitate successful implementation of SOPs, you must prioritize transparent and open communication channels and ensure that all stakeholders are well informed and engaged in the process. Involve key stakeholders at every stage to leverage their insights and perspectives and foster a collaborative approach that improves overall compliance.

Additionally, fostering a culture of continuous improvement is important to improve and optimize SOPs over time. Evolve your processes to meet changing needs by fostering feedback loops, leveraging technological advancements, and staying up-to-date on industry best practices.

Recognize the unique characteristics of your company and tailor your SOP implementation process to perfectly fit your specific needs and existing company culture. The adaptation process not only ensures compliance, but also ensures consistency with your organization’s policies, improving adoption and efficiency.

 

Key advantages of creating a standard operating procedure

Developing and implementing standard operating procedures (SOPs) can provide many benefits to companies across a variety of industries. Here are 10 key benefits:

1.0 Consistency:

Consistency is the key to operational excellence, and standard operating procedures (SOPs) play a critical role in maintaining this essential principle. SOPs serve as a comprehensive framework that promotes consistency and accuracy when executing various tasks, processes, and procedures within an organization. Following established SOPs allows teams to ensure that each step in the workflow follows standardized procedures, ultimately resulting in consistent and predictable results.

The importance of this consistency cannot be underestimated, especially when it comes to maintaining product or service quality. If all team members follow the same guidelines outlined in the SOP, it creates a harmonious workflow that minimizes variation in the end result. This consistency not only improves the overall quality of the final product, but also builds trust among customers and stakeholders because they can expect consistent excellence.

Compliance with SOPs is also critical to meeting regulatory requirements. Different industries have strict guidelines and regulations for their operations. SOPs serve as compliance guidelines and ensure that all work is performed legally and according to industry standards. Not only does this reduce the risk of regulatory violations, but it also provides clear documentation that can prove invaluable during an audit.

Fundamentally, SOPs are not just procedural documents. It serves as the backbone of the effectiveness and efficiency of an organization. By promoting consistency, we help companies build a solid foundation for success to overcome challenges, deliver trustworthy results, and meet the increasing demands of a dynamic market environment.

2.0 Efficiency:

Standard operating procedures (SOPs) play a central role in optimizing organizational processes and serve as comprehensive guidelines that define step-by-step instructions for various tasks. This thoughtful approach not only simplifies processes but also contributes significantly to increasing efficiency in all areas.

Implementation of SOPs contributes significantly to reducing errors in the workflow. By providing a clear, structured roadmap for each task, SOPs act as a strong safeguard against inadvertent errors that can potentially disrupt smooth operations. The resulting reduction in defects reduces the need for corrective action and rework, which has a cascading effect on overall efficiency.

SOPs also serve as a proactive mechanism to prevent deviations from established protocols and ensure that each step in the process is performed consistently and according to predetermined standards. This consistency not only reduces the potential for error, but also promotes a culture of accuracy and reliability within the organizational structure.

Reducing recycling is another practical benefit of implementing SOPs. By providing a roadmap for optimizing task execution, SOPs help reduce the need to repeat tasks due to errors or inconsistencies. This not only saves valuable time, but also contributes to resource optimization, as unnecessary recycling often results in additional costs in terms of time and materials.

Overall, integrating SOPs into organizational processes provides the foundation for increasing operational efficiency. By reducing errors, minimizing rework, and establishing consistent protocols, SOPs contribute to streamlined, optimized workflows and ultimately promote a culture of efficiency and excellence within an organizational environment.

3.0 Training and Onboarding: 

Training and Onboarding: Standard operating procedures (SOPs) play a critical role in thorough training and smooth onboarding of new employees. These carefully crafted documents serve as essential tools to convey the necessary knowledge and skills to new employees, enabling faster and more efficient integration into the organizational structure.

During the onboarding process, SOPs serve as a comprehensive guide and provide a detailed view of the company’s established processes. This not only accelerates the learning curve for new employees, but also ensures a standardized approach across the entire workforce. By providing a structured and organized overview, SOPs help significantly reduce the time it takes for employees to understand the complexities of their roles and responsibilities.

SOPs also play an important role in aligning employees with organizational expectations. Through clear and transparent protocol communication, these documents form the basis for a shared understanding of the company’s values, goals, and operating processes. This coordination is essential to building a cohesive work environment where everyone is on the same page and contributes to a joint effort to achieve common goals.

In short, SOPs go beyond being a simple procedural document and emerge as a dynamic tool that not only provides new employees with the knowledge they need for their roles, but also instills uniformity and consistency within the workforce. As organizations continue to emphasize effective, streamlined onboarding processes, SOPs provide a valuable tool to promote efficiency, consistency, and a cohesive approach to achieving organizational success.

4.0 Compliance:

Compliance with industry regulations, standards and legal requirements is important and standard operating procedures (SOPs) play a critical role in achieving these goals. Carefully written SOPs serve as a comprehensive, documented framework and guidelines that help companies adhere to rigorous quality standards and meet legal obligations.

SOPs serve as a compass for navigating the complex landscape of industry regulations and provide a structured approach to help companies align their practices with legal requirements. By establishing clear processes and protocols, SOPs reduce the risks associated with non-compliance and serve as a proactive tool to ensure that the organization operates within legal limits.

In addition to promoting external compliance, SOPs also contribute significantly to internal consistency and operational efficiency. It serves as a collection of best practices and allows companies to standardize processes and promote consistency of performance. This consistency not only improves overall operational efficiency, but also plays a critical role in maintaining and improving product or service quality.

SOPs also help create a culture of accountability within an organization. By clearly outlining responsibilities and procedures, you ensure employees can perform their jobs accurately and safely, reducing the chance of errors or omissions that could lead to compliance issues. This clarity of roles and responsibilities facilitates the training and onboarding process, ensuring all team members are well-equipped to perform their jobs to established standards.

Additionally, the documentation provided by the SOP is a valuable resource during an audit or inspection. Regulators and external auditors can review these procedures to assess an organization’s commitment to compliance, thereby building trust between stakeholders and regulators. The transparency that SOPs provide not only helps you meet regulatory requirements, but it also helps you build a positive reputation within your industry.

Simply put, an SOP is not just a document. It is an essential tool that helps businesses comply with industry norms, standards, and legal requirements. By providing a solid framework, promoting internal consistency, strengthening accountability, and facilitating audits, SOPs serve as the foundation for a well-regulated and efficient organization.

5.0 Risk Management:

SOPs play a central role in proactively reducing potential risks by providing a comprehensive framework for describing procedures. These standardized procedures are useful tools for identifying and analyzing potential risks in various operational processes. By carefully reviewing each step outlined in the SOP, an organization can identify vulnerabilities and take effective preventive actions.

Carefully detailing the procedures in an SOP provides a concise understanding of the workflow and allows stakeholders to fully assess potential threats and vulnerabilities. This increased awareness allows companies to implement preventive strategies to reduce the likelihood of errors, accidents, and other adverse events. As proactive guidelines, SOPs contribute to a culture of risk awareness and assumptions within the organizational framework.

Additionally, by incorporating input from frontline staff and subject matter experts, SOPs can continually address new risks and adapt to changing situations. This iterative process ensures that risk management remains dynamic and responsive to a changing environment of challenges. When SOPs are regularly updated and communicated throughout the organization, they encourage a shared commitment to safety, operational excellence, and continuous improvement.

Essentially, SOPs form the foundation for maintaining a proactive risk management culture within an organization. By encouraging a systematic and preventative approach, SOPs not only reduce the rate of errors and accidents, but also instill a sense of vigilance and preparedness in employees at all levels. This holistic risk management strategy allows companies to not only protect their assets and reputation, but also improve overall operational resilience.

6.0 Quality Assurance:

Implementing Standard Operating Procedures (SOPs) greatly enhances quality assurance as these documents play an important role in defining the standards of care, details and rigor for performing various tasks in a particular process. By clearly outlining step-by-step procedures and requirements, SOPs serve as a guiding framework to ensure that each task is completed accurately and according to predetermined benchmarks.

The essence of quality assurance lies in meticulous attention to detail and consistent application of standardized procedures. SOPs contribute to this by acting as a comprehensive roadmap that not only outlines the specific steps to be followed but also sets quality levels through clearly defined standards and criteria. These standards are the foundation for creating consistent, high-quality products or services.

SOPs also create a sense of ownership and responsibility among team members by providing a clear understanding of expectations and standards. This transparency promotes a culture of excellence within the organization that empowers employees to consistently meet or exceed established standards.

In the broader context of quality assurance, the role of SOPs goes beyond simple compliance. It serves as a dynamic tool for continuous improvement, allowing companies to evaluate and improve their processes over time. Regularly reviewing and updating SOPs allows companies to adapt to industry standards, technological advancements, and customer expectations, keeping product or service quality at the forefront of organizational priorities.

SOPs also help reduce quality assurance risk by identifying potential areas of deviation or error. By clearly defining correct procedures and specifications, SOPs serve as a preventative measure against deviations that may affect the quality of the final product or service. This proactive approach to risk management increases the overall reliability of the production process.

Fundamentally, integrating SOPs into a quality assurance framework is a strategic investment in consistency, accuracy, and excellence. SOPs provide a structured, standardized approach to operations, allowing companies to maintain the highest quality standards, drive customer satisfaction, and maintain a competitive advantage in the marketplace.

7.0 Communication:

Communication plays a critical role in organizational effectiveness and Standard Operating Procedures (SOPs) have proven to be an essential tool in promoting effective communication in the workplace. These carefully crafted documents not only provide a standardized framework, but also serve as a comprehensive tool to help employees understand and clarify complex processes. By establishing a common language and protocols, SOPs create common understanding among team members and promote smooth communication and collaboration.

Essentially, SOPs serve as a common language that transcends individual interpretation, reducing the risk of misunderstanding. If all team members follow the same procedures outlined in the SOP, this not only ensures consistency but also optimizes communication channels. This common point of reference is especially important in complex workflows where complex details must be communicated accurately.

SOPs also contribute to a culture of transparent and open communication within the organization. Employees can refer to documented procedures for more information about processes, protocols, and expectations. This transparency not only empowers individuals, but also promotes accountability by ensuring everyone is aware of their roles and responsibilities.

SOPs serve as the foundation for effective teamwork by providing a structured, standardized approach to communication. This creates fundamental understanding across departments and levels within the organization. Not only does this promote a collaborative work environment, but it also reduces the risk of misunderstandings and errors, increasing the overall effectiveness of the organization.

In other words, SOPs play a different role in communication within an organization. Not only does it provide a standard language for understanding and discussing processes, it also contributes to transparency, accountability, and collaboration capabilities. Therefore, implementing and adhering to SOPs is an essential part of promoting a consistent and communicative workplace culture.

8.0 Continuous Improvement:

Continuous improvement is promoted through regular review and updating of standard operating procedures (SOPs) that provide feedback and enable seamless integration of continuous improvement. These practices establish and sustain a dynamic organizational culture focused on continuous improvement. By continuously reviewing and revising SOPs, companies create an environment that prioritizes process improvement and optimizes efficiency and effectiveness.

Building a culture of continuous improvement requires not only recognizing the value of feedback, but also actively seeking feedback from a variety of stakeholders. Evaluating your SOPs regularly provides an opportunity to identify areas for improvement, optimize workflow, and implement best practices. This iterative approach allows organizations to adapt to changing circumstances, technological advancements, and industry standards.

Additionally, a commitment to continuous improvement becomes a catalyst for innovation within the organizational structure. Inspire ownership and commitment by encouraging employees to contribute ideas for process optimization. This collaborative approach not only improves existing processes, but also forms the basis for developing creative solutions to new challenges.

By incorporating continuous improvement into your organizational structure, you go beyond simply adhering to established SOPs. This translates into a proactive and visionary approach that sees each iteration of the process as an opportunity for growth. This change in mindset gives the company resilience and allows it to quickly adapt to market changes, customer needs, and internal dynamics.

Ultimately, continuous improvement of SOPs goes beyond routine updates. It is becoming a strategic imperative for organizations that want to not only meet but exceed current standards. These efforts position the organization as an agile, learning entity that prioritizes excellence and innovation in all aspects of its operations.

9.0 Accountability:

Accountability is at the heart of effective organizational processes, and Standard Operating Procedures (SOPs) play a critical role in establishing and reinforcing this essential element. SOPs are more than just guidelines. Responsibilities and roles are carefully assigned within each process, leaving no room for ambiguity. This transparency not only ensures smooth workflow, but also fosters a deep sense of responsibility among employees.

SOPs create a framework that encourages employees to take responsibility for their work and the overall process by clearly defining who is responsible for each step. This increased responsibility acts as a catalyst to increase efficiency and productivity. Employees become more than just artists but active participants in the success of the entire company.

Moreover, the advantage of SOP-centric accountability lies in its proactive nature. With specific people responsible for specific tasks, potential problems can be easily identified and resolved immediately. This will help you tackle challenges head-on and prevent them from developing into bigger problems that could hinder your progress.

Basically, an SOP is not just a document. It is the backbone of a culture of accountability within an organization. When employees understand their roles and take responsibility for their contributions, the organization becomes a well-oiled machine where all components function accurately, leading to ongoing success and continuous improvement.

10.0 Resource Optimization:

Efficient Resource Management: Establishing standard operating procedures (SOPs) plays an important role in improving resource utilization within an organization. By simplifying processes, SOPs help eliminate unnecessary steps and optimize workflow. This leads to significant time savings, cost savings and overall resource efficiency improvements for the company.

The impact of SOPs on resource optimization goes beyond simple procedural standardization. These written procedures guide employees in performing their work accurately and consistently. By identifying and eliminating unnecessary steps, SOPs streamline processes and ensure valuable resources are used for activities that directly contribute to business goals.

One of the major benefits of implementing SOPs is the effort required to maintain them. Organizations must foster a culture of engagement to ensure SOPs are up-to-date, relevant, and reflective of evolving processes. Regular review and updates are essential to ensure SOPs are aligned with the latest industry standards and best practices.

The benefits of SOPs are numerous and include operational efficiency, quality assurance, and regulatory compliance. SOPs improve operational efficiency by providing a structured approach to tasks, reducing errors and promoting consistency. Quality assurance is enhanced by standardizing processes, reducing variability, and increasing confidence in results. SOPs also play an important role in ensuring compliance with industry regulations and standards and protecting your company from legal and regulatory risks.

In essence, an SOP investment is more than just the initial implementation effort. It’s a continuous effort that is rewarded with operational simplification, improved quality, and regulatory compliance. The systematic approach driven by SOP not only improves resource optimization, but also contributes to the overall resilience and success of the organization.

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Relative Response Factor (RRF) & Calculation in HPLC Analysis

Relative Response Factor , High-Performance Liquid Chromatography (HPLC) stands out as a highly influential analytical technique that has found extensive application in diverse fields such as pharmaceuticals, environmental science, and the food industry. Its versatility lies in its ability to efficiently separate, identify, and quantify compounds within intricate mixtures. In the dynamic landscape of analytical methodologies, HPLC has become an indispensable tool for researchers and professionals seeking precision and reliability in their analyses.

Within the realm of HPLC analysis, achieving accurate quantification of analytes represents a pivotal challenge. This necessitates a meticulous consideration of an array of factors that can influence the detector response. Among these influential factors, the Relative Response Factor (RRF) assumes a central role, acting as a linchpin for ensuring the precision and reliability of quantitative results.

The significance of HPLC extends beyond mere separation of compounds; it is intricately linked to the attainment of robust and dependable quantitative data. The inclusion of HPLC in analytical workflows across various industries underscores its reputation as a cornerstone technology. This technique empowers scientists and analysts to unravel the complexities of diverse sample matrices, facilitating a comprehensive understanding of the composition and concentration of compounds within them.

In the pharmaceutical sector, HPLC plays a crucial role in quality control, ensuring the purity and potency of drug formulations. Environmental scientists rely on HPLC to detect and quantify pollutants in air, water, and soil samples, contributing to our understanding of environmental impact and sustainability. Meanwhile, in the food industry, HPLC serves as an essential tool for verifying the safety and authenticity of food products, enabling adherence to regulatory standards.

As analysts navigate the intricacies of HPLC, the meticulous consideration of factors influencing detector response becomes imperative. The Relative Response Factor emerges as a key player in this intricate dance of precision and reliability. It serves as a calibration factor that normalizes the detector response for different compounds, ensuring that quantitative measurements accurately reflect the concentrations of target analytes.

The utilization of HPLC and the careful incorporation of the Relative Response Factor in analytical methodologies embody a commitment to achieving not only separation and identification but also accurate and reliable quantification. This powerful combination positions HPLC as an analytical workhorse, fostering advancements in pharmaceutical research, environmental monitoring, and food safety analysis. As technology evolves, HPLC continues to evolve with it, maintaining its status as an indispensable tool in the analytical scientist’s toolkit.

 

Definition of Relative Response Factor (RRF)

The Relative Response Factor (RRF) plays a crucial role in the realm of High-Performance Liquid Chromatography (HPLC), serving as a corrective measure to address the inherent variations in the response of diverse compounds when subjected to identical chromatographic conditions. This correction is fundamental in achieving precise quantification, as not all compounds manifest an equivalent response to the detector, even when their concentrations are uniform.

In the intricate landscape of chromatographic analysis, the Relative Response Factor serves as a corrective lens, honing the accuracy of quantitative assessments. Its application becomes imperative when striving for a comprehensive understanding of complex samples. The reason lies in the fact that each compound, despite sharing the same concentration within a sample, may exhibit distinctive interactions with the detector, leading to variations in their observed responses.

Consider a scenario where compounds A and B coexist in a sample at identical concentrations. In an ideal world, one might assume that their detector responses would mirror each other precisely. However, reality introduces nuances, as the interaction between a compound and the detector is influenced by its inherent chemical properties. Consequently, Compound A may elicit a stronger or weaker response compared to Compound B under the same chromatographic conditions.

Enter the Relative Response Factor—a pivotal correction factor. By normalizing these disparate responses, the RRF endeavors to rectify the analytical landscape. It acts as a harmonizing force, ensuring that the quantification process is not marred by the idiosyncrasies of individual compounds. Through the application of the RRF, the analyst can transcend the limitations imposed by varying detector sensitivities, thereby obtaining a more faithful and accurate representation of the true quantity of each compound present in the sample.

The Relative Response Factor is the compass that guides the chromatographer through the intricate terrain of compound quantification. Its judicious use transforms HPLC from a realm of potential inaccuracies into a realm of precision, enabling researchers and analysts to unravel the composition of complex mixtures with unparalleled confidence and fidelity.

 

Importance of RRF in HPLC Analysis

The requirement for Relative Response Factors (RRF) is rooted in the fundamental distinctions in the physicochemical characteristics of diverse analytes. These disparities, encompassing factors like molecular structure, molecular weight, and chemical reactivity, contribute to fluctuations in detector response within a high-performance liquid chromatography (HPLC) system. Neglecting to consider these variations can result in the generation of imprecise and unreliable quantitative analyses.

Relative Response Factors play a pivotal role in mitigating these challenges and bolstering the precision and accuracy of quantification in HPLC. By accounting for the inherent differences in analyte properties, RRF serves as a corrective mechanism, ensuring that the quantification process is not compromised by the diverse nature of molecules being analyzed. This meticulous approach not only refines the reliability of results but also contributes to the overall robustness of the analytical methodology.

The implementation of Relative Response Factors acts as a crucial calibration step in HPLC quantification, aligning the analytical system to the unique attributes of each analyte. This nuanced adjustment facilitates a more nuanced and tailored approach, promoting the generation of dependable and scientifically sound results in quantitative analyses. Therefore, acknowledging and incorporating RRF into the analytical workflow becomes indispensable for achieving optimal accuracy and precision in high-performance liquid chromatography methodologies.

 

Calculation of Relative Response Factor (RRF)

The Relative Response Factor is calculated by comparing the detector responses of different compounds under identical chromatographic conditions. The general formula for RRF is:

[1] Response Factor (RF) = Peak Area/ Concentration in mg/ml
[2] Relative Response Factor (RRF) = Response Factor of impurity/Response Factor of API

 

The response is typically measured as peak area or peak height. It’s important to note that the conditions must be strictly controlled, including the column type, mobile phase composition, flow rate, and detector settings, to ensure the accuracy of RRF calculations.

 

Experimental Determination of RRF

The process of determining the Response Factor Ratio (RRF) experimentally entails injecting standard solutions for each compound of interest and subsequently measuring their individual responses. To ensure accuracy, the standard solutions utilized should span a concentration range that aligns with the concentrations found in the actual samples under analysis. By comparing the responses of the two compounds, the RRF can be precisely calculated as the ratio between their respective responses.

For optimal reliability and precision, it is recommended to conduct multiple injections and replicate the analysis. This iterative approach not only provides a more comprehensive understanding of the behavior of the compounds but also contributes to the derivation of a robust and averaged RRF value. By repeating the experimental process, any potential variability or outliers can be identified and addressed, leading to a more accurate representation of the relationship between the compound responses. Consequently, this meticulous methodology enhances the overall validity of the calculated RRF, facilitating more dependable and reproducible results in analytical processes.

 

Applications of Relative Response Factor (RRF) in HPLC Quantification

Multi-Component Analysis

In intricate mixtures, the Relative Response Factor (RRF) plays a pivotal role in ensuring the precise quantification of multiple compounds concurrently. This critical factor serves as a key tool in distinguishing peaks that closely elute from each other in chromatographic analyses. By doing so, it acts as a safeguard against the pitfalls of overestimating or underestimating concentrations, which are common challenges encountered in the analysis of complex samples.

The significance of RRF becomes particularly pronounced in analytical techniques such as chromatography, where numerous compounds coexist within a sample matrix. The intricate nature of these mixtures often leads to peaks that appear in close proximity during elution, making it challenging to accurately discern and quantify individual components. RRF steps in as a quantitative corrective measure, allowing analysts to account for variations in detector response among different compounds.

Through the application of RRF, the analytical process gains enhanced accuracy and reliability. Analysts can confidently navigate through complex chromatograms, resolving overlapping peaks and obtaining precise measurements of each compound’s concentration. This not only contributes to the robustness of analytical results but also ensures the validity and trustworthiness of the data generated.

Moreover, the incorporation of RRF into analytical workflows promotes methodological consistency and harmonization. Analysts can establish standardized approaches for handling diverse sample matrices, confident in the knowledge that RRF will assist in mitigating the inherent challenges posed by complex mixtures. This not only streamlines analytical procedures but also facilitates cross-laboratory comparability, a crucial aspect in scientific research and regulatory compliance.

In summary, the incorporation of Relative Response Factors in the analysis of complex mixtures is indispensable for the accurate quantification of multiple compounds simultaneously. Its role in differentiating closely eluting peaks and preventing the misestimation of concentrations elevates the precision and reliability of analytical results, fostering a robust foundation for scientific inquiry and application.

 

Method Validation

The Relative Retention Factor (RRF) holds a pivotal role in the validation process of High-Performance Liquid Chromatography (HPLC) methods. Its significance lies in its ability to ascertain the suitability of an analytical method for its intended purpose, guaranteeing the delivery of precise and dependable quantitative results.

In the realm of HPLC method validation, the Relative Retention Factor serves as a crucial parameter, contributing to the overall robustness and reliability of the analytical procedure. Its primary function is to validate that the method in question is not only capable of separating target analytes effectively but also of delivering accurate and reproducible quantitative data.

By assessing the relative retention of individual components within a chromatographic system, the RRF ensures that the separation process is both consistent and reliable. This, in turn, validates the suitability of the analytical method for its intended application, whether it be pharmaceutical analysis, environmental monitoring, or any other field where precise and trustworthy quantitative results are imperative.

The incorporation of RRF in HPLC method validation represents a critical step in the quality assurance of analytical procedures. It acts as a safeguard, providing confidence in the method’s ability to meet specific requirements and standards, thereby enhancing the overall integrity of the analytical results generated. The careful consideration and application of RRF contribute significantly to the validation process, reinforcing the credibility of analytical methods in diverse scientific and industrial applications.

 

Quality Control

Within the realms of pharmaceutical and industrial environments, where maintaining the highest standards of product quality is of utmost importance, the Relative Response Factor (RRF) emerges as a pivotal tool in the realm of routine quality control analyses. Its primary function lies in the assurance of the consistency of production processes, playing a critical role in guaranteeing that the final products not only adhere to but surpass the stringent specifications demanded by regulatory standards and industry norms.

In these sophisticated sectors, the utilization of RRF is integral to the fabric of quality assurance protocols. By incorporating RRF into routine analyses, organizations can systematically monitor and assess various aspects of their production processes, creating a robust framework that ensures the uniformity and reliability of each product batch. This meticulous approach is indispensable in mitigating the risks associated with variations in manufacturing, ultimately fortifying the overall quality management system.

The multifaceted applications of RRF extend beyond mere compliance; they extend to optimizing production efficiency. By employing RRF in quality control, companies can identify and rectify deviations early in the manufacturing process, preventing the production of subpar or non-compliant products. This proactive approach not only safeguards the reputation of the company but also contributes to cost-effectiveness and resource utilization.

Moreover, the reliance on RRF underscores a commitment to continuous improvement. Regularly assessing and refining the Relative Response Factor methodology allows organizations to stay abreast of evolving industry standards and technological advancements. This adaptability not only future-proofs operations but also positions companies as leaders in the pursuit of excellence within their respective sectors.

The strategic incorporation of RRF in pharmaceutical and industrial settings transcends the conventional boundaries of quality control; it embodies a comprehensive approach to quality assurance that resonates throughout the entire production lifecycle. By upholding the principles of consistency, compliance, efficiency, and continuous improvement, the utilization of RRF emerges as a cornerstone in the pursuit of excellence in the creation of pharmaceutical and industrial products.

 

Challenges and Considerations

Although the Relative Response Factor (RRF) proves to be an indispensable tool in the realm of High-Performance Liquid Chromatography (HPLC) analysis, its efficacy is not immune to certain challenges. These challenges predominantly stem from dynamic factors inherent in the HPLC system, such as fluctuations in column performance, deviations in detector sensitivity, and shifts in the composition of the mobile phase. These variables introduce a level of variability in RRF values, thereby necessitating vigilant oversight and maintenance practices.

The sensitivity of the HPLC system to changes in column performance is a critical consideration, as alterations in column efficiency can directly impact the reliability of RRF values. Likewise, variations in detector sensitivity can introduce inconsistencies, underscoring the need for meticulous monitoring and periodic recalibration to ensure accurate and reproducible results. Additionally, the mobile phase composition, a fundamental component of the HPLC process, is susceptible to changes that can affect the interactions between analytes and the stationary phase, thereby influencing RRF values.

To mitigate these challenges and uphold the accuracy of quantitative HPLC analysis, it is imperative to implement routine system suitability tests. These tests serve as a proactive measure to assess the overall performance of the HPLC system, identify any deviations, and allow for timely corrective actions. Furthermore, recalibration, a systematic process of fine-tuning instrument parameters and standards, becomes indispensable to counteract the impact of changing variables on RRF values.

While RRF remains an invaluable asset in HPLC analysis, the dynamic nature of the chromatographic system necessitates a comprehensive approach to quality control. Through regular system suitability tests and recalibration, analysts can fortify the reliability of RRF values, ensuring the precision and accuracy required for robust quantitative HPLC analysis.

 

Conclusion

To summarize, the Relative Response Factor (RRF) holds paramount importance in the realm of High-Performance Liquid Chromatography (HPLC), playing a pivotal role in ensuring the precision and dependability of quantitative outcomes. The computation of this factor entails a meticulous examination of detector responses for diverse compounds, all conducted under tightly controlled conditions. The versatility of RRF is evidenced by its extensive utilization in diverse applications such as multi-component analysis, method validation, and quality control, establishing it as an indispensable tool within the domain of modern analytical chemistry.

The significance of RRF becomes apparent in its contribution to the accuracy of quantitative results, a characteristic that is imperative for reliable conclusions in HPLC experiments. By scrutinizing and comparing detector responses under standardized conditions, RRF enables researchers and analysts to account for variations in compound detection, thereby refining the precision of measurements.

Furthermore, the widespread applications of RRF extend beyond singular compound analysis, finding relevance in the complex landscape of multi-component analyses. Its utility in method validation ensures the robustness and reliability of analytical procedures, instilling confidence in the outcomes generated through HPLC methodologies. In the context of quality control, RRF serves as a key metric for assessing the consistency and accuracy of analytical processes, thereby safeguarding the integrity of experimental data.

As we move forward in the era of advancing technology, it is reasonable to anticipate continuous refinement in the methods used for RRF determination. Technological progress may lead to enhanced precision and expanded versatility in HPLC analysis across various industries. These refinements could involve the integration of cutting-edge instrumentation, automation, and data analysis techniques, all aimed at elevating the standards of accuracy and reliability in the field of analytical chemistry.

In essence, the Relative Response Factor stands as a linchpin in the world of HPLC, ensuring that quantitative results are not only accurate but also reliable, thereby underlining its indispensable role in contemporary analytical chemistry practices. The evolving landscape of technology promises a future where further advancements in RRF determination methods will continue to push the boundaries of precision, ultimately benefiting a wide array of industries reliant on HPLC for intricate analytical processes.

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Sterile Pharmaceutical Manufacturing Key Challenges

Sterile Pharmaceutical Manufacturing, Within the realm of sterile pharmaceutical manufacturing, which is widely regarded as an epitome of sophisticated processes, a tapestry of challenges unfolds, underscoring the intricate dance between precision and complexity. Despite the cutting-edge nature of this manufacturing domain, a host of nuanced problems emerge, often evolving into more serious complications than their initial manifestations suggested.

 

[1] Cleanliness
[2] Sterility assurance
[3] Compliance, and
[4] Safety

Cleanliness in Sterile Pharmaceutical Manufacturing

In Sterile Pharmaceutical Manufacturing, Maintaining an immaculate environment serves as the foremost guardian in the realm of sterile pharmaceutical manufacturing, representing a matter of paramount importance. The smallest particles of contaminants wield the potential to derail the entire manufacturing process, leaving pharmaceutical products vulnerable to compromised quality and efficacy. Achieving an environment untainted by impurities becomes an intricate and highly meticulous endeavor, necessitating unwavering vigilance and strict adherence to rigorous standards. In this pursuit, the emphasis lies on establishing and sustaining an environment that not only meets but surpasses the stringent cleanliness requirements essential for ensuring the integrity and safety of pharmaceutical products throughout their manufacturing journey.

 

Sterility assurance in Sterile Pharmaceutical Manufacturing

Sterile Pharmaceutical Manufacturing ensure sterility is the second pivotal pillar in the pharmaceutical manufacturing process, embodying a paramount commitment to upholding an aseptic environment at every stage of production. The preservation of sterility is of utmost importance as any breach in this crucial barrier carries profound implications, posing a serious threat to the safety and efficacy of pharmaceutical products and, consequently, the well-being of end-users. The attainment and perpetuation of sterility require not merely cutting-edge technology, but also an in-depth comprehension of microbiology and unwavering adherence to meticulous procedural protocols.

Maintaining sterility assurance is a complex and multifaceted undertaking, involving a constant and rigorous effort to prevent the introduction of contaminants that could compromise the integrity of pharmaceutical formulations. This dedication extends from the initial stages of raw material handling through to the final packaging of the finished products. Every facet of the manufacturing process is scrutinized to identify and mitigate potential sources of contamination.

The significance of sterility assurance becomes even more pronounced when considering the potential consequences of a breach. Any compromise in the sterility of pharmaceutical products can lead to contamination, rendering them unsafe for consumption or use. This not only poses a direct risk to the health of individuals relying on these medications but also undermines the reputation of the pharmaceutical manufacturer and erodes trust within the healthcare community.

The pursuit of sterility involves a symbiotic integration of advanced technological tools, such as state-of-the-art cleanroom facilities and automated systems, with a profound understanding of microbiological principles. This holistic approach encompasses the design of facilities to minimize the presence of microorganisms, the rigorous validation of sterilization processes, and the implementation of stringent monitoring systems to promptly identify and rectify any deviations from sterility norms.

Moreover, achieving and sustaining sterility requires a culture of unwavering commitment to quality and a relentless focus on continuous improvement. The personnel involved in the manufacturing process must undergo thorough training to comprehend the intricacies of microbiological control and the critical role they play in safeguarding the purity of pharmaceutical products. Regular audits, inspections, and ongoing research contribute to the refinement of protocols and the adaptation of emerging technologies to fortify the sterility assurance framework.

Sterility assurance stands as a cornerstone in pharmaceutical manufacturing, demanding an intricate interplay of cutting-edge technology, microbiological expertise, and stringent procedural adherence. The commitment to maintaining an aseptic environment is not just a regulatory requirement but a profound responsibility to ensure the safety, efficacy, and integrity of pharmaceutical products, thereby safeguarding the health and trust of the end-users.

 

Compliance in Sterile Pharmaceutical Manufacturing

Sterile Pharmaceutical Manufacturing, Compliance as the third crucial pillar, directs our attention to the intricate web of regulations and standards intricately woven around the realm of pharmaceutical manufacturing. This labyrinth demands a comprehensive understanding not only of regional but also international guidelines. Successfully navigating this complex landscape is a multifaceted challenge that extends beyond mere regulatory adherence; it is an unwavering commitment to the ethical production of pharmaceuticals. This commitment transcends the confines of procedural checkboxes; it emerges as a profound dedication to safeguarding the safety and well-being of the global population.

To embark on the journey of compliance is to delve into a dynamic and ever-evolving framework of rules and norms that govern the entirety of pharmaceutical operations. From research and development to production and distribution, each stage of the pharmaceutical lifecycle is meticulously scrutinized by a myriad of regulatory bodies and international organizations. This requires not only staying abreast of the latest updates but also actively participating in shaping and influencing the development of these standards.

In essence, compliance is not a static concept but a living, breathing entity that adapts to the changing landscape of healthcare, technology, and societal needs. It necessitates constant vigilance, continuous improvement, and a proactive approach to anticipate and address emerging challenges. It is the cornerstone of responsible and sustainable pharmaceutical practices, fostering an environment where innovation and safety coexist harmoniously.

Moreover, the commitment to compliance extends beyond the mere fulfillment of legal obligations. It is a moral and ethical responsibility that transcends borders and cultures. It involves not just meeting the minimum requirements but striving for excellence in ensuring the quality, safety, and efficacy of pharmaceutical products. This commitment underscores an unwavering dedication to the highest standards of integrity, transparency, and accountability in every facet of pharmaceutical manufacturing.

In the grand tapestry of pharmaceutical compliance, a holistic perspective is indispensable. It involves understanding the interconnectedness of global health, economic considerations, and environmental impact. Compliance is not an isolated endeavor; it is a collaborative effort that requires engagement with stakeholders at every level — from regulatory agencies and industry partners to healthcare professionals and, most importantly, the end-users.

In conclusion, compliance in pharmaceutical manufacturing is not a mere regulatory obligation; it is a comprehensive commitment to navigating the intricate web of rules and norms with a steadfast dedication to ethical practices. It entails embracing a dynamic and evolving landscape, upholding the highest standards of quality, and fostering a global culture of responsibility for the well-being of humanity.

 

Safety in Sterile Pharmaceutical Manufacturing

Sterile Pharmaceutical Manufacturing, Safety often considered the fourth dimension in pharmaceutical manufacturing, stands as a comprehensive shield safeguarding both the individuals involved in the production process and the ultimate consumers of pharmaceuticals. This protective umbrella extends far beyond a mere compliance with regulatory standards, evolving into a moral imperative deeply embedded in the core values of responsible pharmaceutical manufacturing.

Delving into the intricate realm of sterile pharmaceutical manufacturing, one quickly recognizes that the seamless integration of cleanliness, sterility assurance, compliance, and safety is not a mere technical obligation but a symphony of interconnected elements. Each component, from the ergonomic layout of production facilities to the meticulous adherence to stringent safety protocols, undergoes rigorous scrutiny to identify and mitigate potential hazards. This multifaceted approach underscores the industry’s commitment not only to scientific progress but, perhaps more significantly, to the unwavering protection of public health.

The challenges encountered in sterile pharmaceutical manufacturing represent a complex tapestry where cleanliness, compliance, and safety interweave to create a harmonious orchestration. Navigating these challenges successfully becomes emblematic of an industry dedicated not only to advancing scientific knowledge but also to upholding a solemn duty to ensure the well-being of the global population reliant on the benefits of modern medicine.

Beyond meeting regulatory requirements, prioritizing safety becomes a beacon guiding pharmaceutical manufacturers toward the highest standards of quality. By understanding and proactively addressing these hurdles, the pharmaceutical industry not only produces pharmaceuticals that meet the stringent criteria of excellence but also establishes itself as a trustworthy custodian of public health. In doing so, pharmaceutical products emerge not just as commodities but as vital components in a global network of health and well-being, fostering trust and reliability among a population dependent on the advancements of modern medicine.

 

What challenges exist in the realm of sterile pharmaceutical manufacturing?

Sterile Pharmaceutical Manufacturing, Sterile pharmaceutical manufacturing is fraught with a myriad of challenges that, if left unaddressed, can have severe consequences, including hazardous infections and the compromise of the integrity of pharmaceutical products. One of the most pervasive issues in this realm is the specter of cross-contamination, wherein various strains of bacteria from external sources infiltrate the production environment, thereby triggering the proliferation of harmful microorganisms. The repercussions of such contamination are profound, posing grave health risks to both the diligent workers engaged in the manufacturing process and the unsuspecting consumers reliant on the medications thus compromised.

Equally significant is the threat of contamination stemming from human error within the sterile pharmaceutical manufacturing process. Instances where employees inadvertently make mistakes during the handling and processing of drugs can usher in bacteria, leading to contamination of the pharmaceutical products. The potential ramifications of such errors are dire, exposing end-users to serious health complications and underscoring the critical need for stringent quality control measures.

To effectively tackle these pervasive challenges, manufacturers must institute a comprehensive and well-structured system for monitoring and tracking data pertaining to drug production. This proactive approach is indispensable in identifying any deviations or irregularities in the manufacturing process promptly. By leveraging advanced monitoring technologies and robust data tracking systems, manufacturers can establish a vigilant oversight mechanism that not only detects potential issues but also facilitates the swift implementation of corrective measures.

Central to this strategy is the real-time surveillance of critical parameters, such as environmental conditions, equipment performance, and personnel adherence to standardized protocols. Regular audits and assessments further contribute to the early detection of anomalies, enabling manufacturers to proactively address any potential sources of contamination. This holistic monitoring system serves as a bulwark against the insidious threats posed by cross-contamination and human error, safeguarding the integrity of sterile pharmaceutical manufacturing processes.

Moreover, the implementation of an effective data tracking system empowers manufacturers to trace the entire lifecycle of a pharmaceutical product, from raw material procurement to distribution. This traceability not only enhances accountability but also facilitates targeted interventions at various stages of the production chain. By systematically collecting and analyzing data, manufacturers gain valuable insights into potential risk factors and areas for improvement, thereby fostering continuous refinement of their manufacturing processes.

The multifaceted challenges inherent in sterile pharmaceutical manufacturing demand a proactive and comprehensive approach. By prioritizing robust monitoring systems and meticulous data tracking, manufacturers can fortify their defenses against cross-contamination and human error, ensuring the production of pharmaceuticals that meet the highest standards of safety and efficacy. This commitment to quality control is not only a regulatory imperative but a fundamental ethical responsibility to protect the well-being of both industry professionals and the broader community relying on these essential medications.

 

Origins of the Issues

Sterile Pharmaceutical Manufacturing, the intricate realm of sterile pharmaceutical manufacturing revolves around the meticulous creation of products devoid of any contaminants, a critical imperative for ensuring the safety and efficacy of pharmaceuticals. Despite the imperative nature of this objective, the industry contends with a pervasive challenge—contamination—a multifaceted issue stemming from diverse sources within the manufacturing process.

Contaminants infiltrate the sterile pharmaceutical manufacturing process through various avenues, ranging from the inadvertent introduction by personnel working within the facility to potential impurities inherent in the equipment employed and, remarkably, the products themselves. This omnipresent risk poses a considerable threat to the quality and safety of pharmaceuticals, necessitating vigilant measures to mitigate potential adverse consequences.

The consequences of contamination within sterile pharmaceutical manufacturing are far-reaching and extend beyond mere inconveniences. A paramount concern is the potential for adverse reactions in individuals consuming the pharmaceutical products. Contamination can introduce foreign elements capable of triggering allergic reactions or other adverse responses, thereby jeopardizing the well-being of patients.

Furthermore, contamination poses a formidable obstacle to the production of high-quality pharmaceuticals. The presence of impurities can compromise the integrity and effectiveness of the intended pharmaceutical formulations, leading to suboptimal or even harmful outcomes. This not only undermines the manufacturer’s ability to deliver reliable products but also erodes the trust and confidence of consumers in the pharmaceutical industry.

Perhaps most alarming is the potential for contamination to spawn new viruses or other harmful agents. In an era where global health crises underscore the urgency of maintaining stringent safety measures, the inadvertent creation or propagation of pathogens within pharmaceutical manufacturing facilities is a scenario that demands meticulous attention and preventive strategies.

In response to these challenges, the pharmaceutical industry has implemented a spectrum of measures designed to uphold the sterility of the manufacturing process. Foremost among these is the utilization of rigorous sterilization methods capable of eliminating contaminants across diverse categories. This includes protocols effective against microbial agents, particulate matter, and other potential impurities.

Additionally, proactive safety protocols have become integral components of sterile pharmaceutical manufacturing. These protocols are designed not only to rectify contamination issues but, more importantly, to prevent them from occurring in the first place. Stringent hygiene practices, controlled environments, and thorough training of personnel contribute to creating an aseptic manufacturing environment that minimizes the risk of contamination.

In essence, sterile pharmaceutical manufacturing is a highly intricate process that demands relentless dedication to maintaining product integrity. The ongoing pursuit of advanced sterilization techniques and the steadfast adherence to rigorous safety protocols collectively serve as bulwarks against contamination, safeguarding the quality, safety, and reliability of pharmaceutical products for the benefit of global health.

 

Problem Resolutions

Sterile Pharmaceutical Manufacturing, in the realm of sterile pharmaceutical manufacturing, a myriad of challenges plague the industry, giving rise to critical safety concerns that necessitate immediate attention. Foremost among these issues is the pervasive problem of cross-contamination, a perilous occurrence wherein bacteria inadvertently infiltrate different stages of the manufacturing process, posing a substantial threat to the production of pharmaceuticals. The ramifications of such contamination are dire, with the potential to culminate in life-threatening infections, thereby accentuating the gravity of safety concerns within this domain.

A parallel predicament in sterile pharmaceutical manufacturing involves the mishandling of vaccines, a complex process that demands utmost precision and diligence. The consequences of mismanagement extend beyond the mere compromise of vaccine efficacy; it opens the door to the creation of hazardous viruses, contributing significantly to safety apprehensions. Furthermore, instances of injuries stemming from improper vaccine storage, laboratory accidents, and even intentional sabotage exacerbate the existing safety issues, underscoring the urgent need for comprehensive solutions.

To address these formidable challenges, manufacturers must implement a multifaceted approach. First and foremost, stringent measures must be taken to ensure the impeccable design and vigilant monitoring of manufacturing processes. This involves a meticulous review and refinement of existing protocols to minimize the risk of cross-contamination. Equally crucial is the implementation of robust sterilization procedures for equipment, creating a barrier against the infiltration of harmful bacteria and contaminants.

In addition, manufacturers must prioritize the development of sophisticated systems capable of tracking instances of cross-contamination and vaccine mishandling. Real-time monitoring tools can enable swift detection of anomalies, facilitating prompt corrective action. This proactive approach not only mitigates potential risks but also bolsters the overall safety profile of sterile pharmaceutical manufacturing.

In conclusion, the multifaceted challenges of cross-contamination and vaccine mishandling in sterile pharmaceutical manufacturing necessitate a comprehensive and proactive strategy. By adopting rigorous process design, vigilant equipment sterilization, and advanced monitoring systems, manufacturers can fortify their commitment to safety, thereby safeguarding the integrity of pharmaceutical production and protecting the well-being of the end-users.

 

Conclusion

In the realm of sterile pharmaceutical manufacturing, the establishment of crucial elements is imperative to guarantee the utmost quality of the manufactured products. This article delves into the paramount considerations essential for maintaining the quality standards of sterile pharmaceuticals. By thoroughly examining and addressing the prominent challenges that may arise during the manufacturing process, we aim to provide comprehensive insights into effective solutions.

One of the primary concerns in sterile pharmaceutical manufacturing revolves around potential pitfalls that can compromise the quality of the end products. To elucidate, the risk of contamination, both microbial and particulate, looms large and can significantly impact the integrity of pharmaceutical formulations. Identifying and implementing stringent measures to counteract these contamination risks is of utmost importance.

Additionally, the maintenance of a controlled environment is pivotal in sterile manufacturing facilities. Fluctuations in temperature, humidity, and air quality can adversely affect the stability of pharmaceutical compounds, leading to potential efficacy issues. Therefore, a comprehensive assessment of environmental controls and the implementation of robust monitoring systems are crucial steps in safeguarding product quality.

Furthermore, the article explores the complexities associated with aseptic processing, a critical aspect of sterile pharmaceutical manufacturing. Challenges such as maintaining sterility throughout the entire production process and ensuring the proper functioning of aseptic equipment demand meticulous attention. Strategies and best practices for optimizing aseptic processing are examined to minimize the risk of microbial contamination and uphold the highest standards of product quality.

By addressing these challenges head-on and incorporating effective measures, manufacturers not only uphold the quality of their pharmaceuticals but also stand to realize cost reductions. A streamlined and well-controlled manufacturing process not only enhances product quality but also minimizes the need for corrective actions, thereby mitigating associated expenses. The symbiotic relationship between quality assurance and cost-effectiveness underscores the importance of a holistic approach to sterile pharmaceutical manufacturing.

In conclusion, this article provides a comprehensive exploration of the multifaceted challenges within sterile pharmaceutical manufacturing and offers practical insights into mitigating these challenges. By embracing a proactive and meticulous approach, manufacturers can fortify their processes, ensuring both the quality of their products and potential cost savings—a dual benefit that underscores the critical importance of maintaining excellence in sterile pharmaceutical manufacturing.

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Inverse Benefit Law in the Pharmaceutical Industry

Inverse Benefit Law, the pharmaceutical industry plays a crucial role in the global healthcare landscape, striving to develop innovative drugs and therapies to address a myriad of medical conditions. Amidst the pursuit of scientific advancements and breakthroughs, the concept of the Inverse Benefit Law emerges as a significant consideration within this sector. This principle, rooted in the notion that the benefits derived from a pharmaceutical product may be inversely related to its necessity, poses both ethical and economic challenges. This essay delves into the intricacies of the Inverse Benefit Law in the context of the pharmaceutical industry, exploring its implications on drug development, market dynamics, and societal well-being.

Understanding Inverse Benefit Law:

The Inverse Benefit Law, as applied to the pharmaceutical sector, posits that the potential benefits of a drug are often inversely related to the prevalence or severity of the medical condition it aims to treat. In simpler terms, drugs designed to address less prevalent or severe diseases may yield higher financial returns for pharmaceutical companies, creating a paradox where profitability is detached from the societal impact of the drug.

Pharmaceutical companies are profit-driven entities, necessitating a careful balance between business goals and societal well-being. The Inverse Benefit Law raises questions about the alignment of economic incentives with public health needs, as it suggests that the financial success of a drug may not necessarily correspond to its significance in addressing widespread health concerns.

Economic Incentives and Drug Development:

The pharmaceutical industry operates within a complex economic landscape, where the costs associated with research and development play a crucial role in shaping drug pricing and marketing strategies. The process of bringing a new drug to market involves significant financial investments in various stages, including initial research, extensive clinical trials, and obtaining regulatory approvals. This intricate web of expenses and incentives often leads pharmaceutical companies to make strategic decisions that can have far-reaching implications.

The Inverse Benefit Law introduces a dynamic element into this equation. According to this concept, there is a tendency for companies to prioritize the development of drugs for niche markets or rare diseases. The rationale behind this prioritization lies in the potential for obtaining exclusivity rights and setting higher prices for drugs addressing these specific, often underserved, medical conditions. By focusing on niche markets, pharmaceutical companies may see a greater return on investment due to reduced competition and the ability to command premium prices.

One tangible manifestation of the Inverse Benefit Law is the orphan drug designation. This designation is intended to incentivize the development of drugs for rare diseases, providing pharmaceutical companies with certain benefits, such as extended market exclusivity and tax credits. While the orphan drug designation has undeniably spurred innovation in addressing neglected medical conditions, it simultaneously raises concerns regarding the accessibility and affordability of these drugs.

On the positive side, the orphan drug designation has stimulated research and development efforts for diseases that might otherwise be overlooked due to their rarity. Patients suffering from these rare conditions have witnessed an increase in the availability of therapeutic options tailored to their specific needs. However, the flip side of this scenario involves potential challenges related to the pricing and accessibility of these drugs.

Given the exclusive market rights granted to companies developing orphan drugs, there is a risk that the resulting medications may be priced at levels that pose financial burdens for patients and strain healthcare systems. The limited patient population for rare diseases may not provide the economies of scale seen with more prevalent conditions, making it challenging for pharmaceutical companies to recoup their development costs without setting higher prices.

As a result, the Inverse Benefit Law prompts a critical discussion about the balance between incentivizing innovation and ensuring widespread access to essential medications. Policymakers, healthcare professionals, and industry stakeholders must navigate this delicate equilibrium to guarantee that the pharmaceutical landscape fosters both innovation and affordability, ultimately serving the best interests of patients and society as a whole.

Market Dynamics and Access to Medicines:

The Inverse Benefit Law, also known as the “Matthew Effect” in the context of healthcare and pharmaceuticals, is a concept that posits the distribution of resources and benefits in a way that seems counterintuitive to common expectations. In the realm of pharmaceuticals, this principle suggests that the allocation of research and development resources tends to favor diseases prevalent in affluent populations rather than those affecting lower-income regions. This dynamic has far-reaching implications for global health, market dynamics, and the accessibility of medicines.

One of the primary consequences of the Inverse Benefit Law in the pharmaceutical industry is the potential exacerbation of global health inequalities. Pharmaceutical companies, driven by profit motives, may channel their resources towards developing drugs for diseases that afflict wealthier demographics. This strategic decision can lead to a relative neglect of health issues prevalent in low-income regions, where the purchasing power and market potential may be limited.

This selective allocation of resources contributes to a scenario where the most profitable drugs may not align with the most pressing health needs on a global scale. Diseases that disproportionately affect the poor may receive insufficient attention and research investment, hindering the development of affordable and effective treatments for conditions that carry significant public health burdens.

Furthermore, the pricing strategies associated with drugs developed under the Inverse Benefit Law can create significant barriers to accessibility. High prices, particularly for niche drugs with limited competition, can render these medications financially out of reach for a substantial portion of the population. This not only affects individual patients but also strains healthcare systems as they grapple with the economic burden of providing expensive treatments.

Balancing the pursuit of profitability with the imperative of ensuring drug affordability becomes a critical challenge for the pharmaceutical industry. Striking this balance is essential not only for ethical reasons but also for the overall well-being of global populations. Policymakers, regulators, and the industry itself must navigate this delicate equilibrium to ensure that pharmaceutical innovation addresses not only the needs of profitable markets but also the broader spectrum of global health challenges.

Addressing the ethical considerations surrounding the Inverse Benefit Law requires a reevaluation of the priorities and incentives within the pharmaceutical industry. This may involve implementing policies that encourage research and development for neglected diseases, providing incentives for the development of affordable medications, and fostering collaborations between public and private sectors to address health disparities. Ultimately, understanding and mitigating the impact of the Inverse Benefit Law is crucial for fostering a more equitable and accessible healthcare landscape worldwide.

Ethical Considerations and Corporate Social Responsibility:
The ethical dimension of the Inverse Benefit Law underscores the importance of examining and reevaluating the corporate social responsibility (CSR) practices of pharmaceutical companies. The Inverse Benefit Law, a concept suggesting that the individuals who need a drug the most may receive the least benefit from it, brings to light the moral considerations surrounding the pharmaceutical industry. In navigating the intricate balance between profit motives and public health, ethical decision-making becomes imperative.

Expanding the perspective on corporate responsibility involves delving into the societal impact of pharmaceuticals. Beyond mere profitability, companies should take into account the broader consequences of their products on communities and individuals. This entails considering factors such as equitable access to medications and addressing the specific needs of underserved populations. It shifts the focus from a purely profit-driven model to one that embraces a more holistic approach, aligning business practices with ethical considerations.

The role of governments, regulatory bodies, and advocacy groups is instrumental in shaping the ethical landscape of the pharmaceutical industry. Policymakers can implement measures that incentivize the development of drugs for both common and rare diseases, addressing the disparities highlighted by the Inverse Benefit Law. By fostering an environment that promotes transparency in pricing structures, stakeholders can ensure that the cost of medications is reasonable and justifiable. This transparency not only serves to build trust among consumers but also contributes to a fair and ethical pharmaceutical market.

Collaborations between public and private entities stand out as a critical strategy in mitigating the adverse effects of the Inverse Benefit Law. Joint efforts can lead to the development of drugs that cater to a wider range of medical needs, including those that might be overlooked in a purely profit-driven model. Such partnerships can harness the strengths of both sectors, combining innovation, resources, and expertise to address health challenges more effectively.

Moreover, an ethical approach involves acknowledging the global nature of public health issues. It requires pharmaceutical companies to recognize the disparities in healthcare access between developed and developing regions and actively work towards narrowing these gaps. This might involve differential pricing strategies, where medications are priced in a way that considers the economic conditions of different countries.

The ethical dimension of the Inverse Benefit Law prompts a comprehensive reevaluation of pharmaceutical companies’ CSR practices. This involves adopting a broader perspective that considers societal impacts, ensuring equitable access to medications, and addressing the unique healthcare needs of marginalized populations. Collaboration between public and private entities, transparent pricing structures, and government policies incentivizing drug development for diverse medical conditions are essential components of an ethical pharmaceutical industry committed to balancing profit motives with public health priorities.

The Inverse Benefit Law introduces a captivating concept that challenges the conventional wisdom within the pharmaceutical industry, shedding light on a complex interplay between societal impact and financial success. Traditionally, the assumption has been that the greater the societal impact of a pharmaceutical product, the greater its financial success. However, the Inverse Benefit Law suggests a paradoxical dynamic where, in certain cases, the drugs with the greatest potential to benefit society may not generate the highest profits.

In the face of evolving healthcare landscapes and heightened scrutiny, grappling with the implications of this principle becomes imperative for stakeholders in the pharmaceutical industry. The delicate task of balancing economic incentives with public health imperatives requires a comprehensive and collaborative effort from pharmaceutical companies, governmental bodies, and the broader healthcare ecosystem.

The ethical imperative of addressing the Inverse Benefit Law goes beyond altruism; it is a pragmatic approach to ensuring the long-term sustainability and legitimacy of the pharmaceutical industry. As the industry faces increasing pressures to demonstrate its commitment to public welfare, aligning financial success with societal impact becomes crucial for maintaining trust and credibility.

Achieving this balance necessitates a multifaceted approach. Pharmaceutical companies must go beyond profit-driven motivations and embrace ethical business practices, placing a higher premium on transparency, integrity, and patient-centricity. Governments play a pivotal role in creating regulatory frameworks that incentivize companies to prioritize public health, perhaps through mechanisms such as extended patent exclusivity for drugs with significant societal impact.

Furthermore, the broader healthcare ecosystem, including healthcare providers, advocacy groups, and the academic community, must actively engage in shaping a landscape that values accessibility, affordability, and innovation. Collaborative initiatives can foster an environment where pharmaceutical companies are encouraged to invest in research and development that addresses unmet medical needs and ensures that breakthroughs are accessible to a wider population.

The journey toward a more equitable and accessible pharmaceutical landscape demands a commitment to social responsibility. This involves not only addressing the affordability of medications but also engaging with communities to understand their unique healthcare challenges and tailoring solutions that genuinely benefit humanity.

In essence, the Inverse Benefit Law serves as a call to action, urging the pharmaceutical industry to transcend conventional profit-driven paradigms. The integration of ethical considerations, social responsibility, and a genuine commitment to innovation that addresses the diverse health needs of global populations is not just a moral obligation but a strategic imperative for the sustained success of the industry in a rapidly evolving healthcare landscape.

Factors Affecting the Inverse Benefit Law in the Pharmaceutical Industry

The pharmaceutical industry plays a pivotal role in global healthcare, contributing to the development and production of medications that improve and save lives. However, the Inverse Benefit Law (IBL) poses a complex challenge within this industry. The IBL suggests that the benefits derived from a pharmaceutical product are inversely related to its level of need or importance within a population. In other words, drugs that address less prevalent or chronic conditions may receive less attention and funding compared to medications for more acute and widespread diseases. This essay explores the multifaceted factors influencing the Inverse Benefit Law within the pharmaceutical sector.

Market Dynamics:

One of the primary factors contributing to the Inverse Benefit Law is the market-driven nature of the pharmaceutical industry. Companies are profit-driven entities, and their decisions are often influenced by market demand and potential financial returns. Medications addressing prevalent conditions, such as cardiovascular diseases or diabetes, tend to attract more investment as they cater to larger patient populations, ensuring a broader market and higher revenue potential.

Conversely, drugs targeting rare diseases or conditions affecting a smaller percentage of the population may face limited market prospects. The low prevalence of these conditions can result in a smaller patient base, reducing the potential profits for pharmaceutical companies. As a result, the Inverse Benefit Law manifests when companies allocate resources disproportionately, favoring medications that address more common ailments.

Research and Development Costs:

The high costs associated with pharmaceutical research and development (R&D) contribute significantly to the Inverse Benefit Law. Developing a new drug requires extensive financial investment and resources, and pharmaceutical companies naturally prioritize projects that promise a more immediate and lucrative return on investment. This financial consideration leads companies to focus on diseases with higher prevalence, where the potential for profit is greater.

Additionally, the complex nature of researching and developing treatments for rare diseases often involves more challenges and uncertainties. The smaller patient pool for clinical trials and the limited understanding of these conditions can extend the timeline and increase the cost of bringing a drug to market. Consequently, pharmaceutical companies may be less inclined to invest in these projects, perpetuating the Inverse Benefit Law.

Regulatory Environment:

The regulatory landscape also plays a crucial role in shaping the Inverse Benefit Law within the pharmaceutical industry. Regulatory agencies, such as the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA), impose stringent requirements for drug approval. The regulatory pathway for drugs addressing rare diseases may differ from that for more common conditions, often requiring additional evidence of efficacy and safety.

The increased regulatory burden for rare disease drugs can be a deterrent for pharmaceutical companies, adding complexity and cost to the development process. This, in turn, reinforces the tendency to focus on drugs targeting prevalent conditions that align more closely with established regulatory pathways. As a result, the regulatory environment contributes to the Inverse Benefit Law by influencing the allocation of resources and attention within the pharmaceutical sector.

Public Health Priorities:

The prioritization of public health needs and government policies also affects the manifestation of the Inverse Benefit Law. Public health agencies and policymakers are often compelled to address widespread health concerns that pose significant societal burdens. Conditions with high morbidity and mortality rates, such as infectious diseases or epidemics, may take precedence in public health agendas.

Consequently, pharmaceutical companies may align their research and development efforts with the prevailing public health priorities, focusing on medications that address immediate and widespread threats. This alignment with public health agendas can inadvertently marginalize the development of drugs for less common conditions, contributing to the Inverse Benefit Law.

Economic Considerations

Economic factors, both at the macro and micro levels, contribute to the Inverse Benefit Law within the pharmaceutical industry. Countries with limited healthcare budgets may prioritize the allocation of resources to address prevalent conditions that impose a higher economic burden on the healthcare system. This can influence pharmaceutical companies to direct their efforts towards developing drugs that align with the economic priorities of healthcare systems.

Furthermore, economic considerations impact the pricing and reimbursement strategies for pharmaceutical products. Drugs addressing more common conditions often benefit from economies of scale, enabling companies to set lower prices while maintaining profitability. In contrast, drugs for rare diseases may face challenges in achieving cost-effectiveness, further perpetuating the Inverse Benefit Law.

The Inverse Benefit Law presents a complex challenge within the pharmaceutical industry, where market dynamics, research and development costs, regulatory environments, public health priorities, and economic considerations collectively shape the allocation of resources. To address this issue, stakeholders, including pharmaceutical companies, regulatory agencies, and policymakers, must work collaboratively to create incentives for the development of medications for rare and neglected diseases. Initiatives such as orphan drug designations, research grants, and regulatory pathways tailored for rare diseases can help mitigate the impact of the Inverse Benefit Law, fostering a more equitable distribution of resources and promoting the development of innovative therapies for a diverse range of medical conditions.

Exploring the Dichotomy: Inverse Benefit and Ethics

In the complex landscape of human behavior, two concepts that often emerge in discussions about societal values and decision-making are “inverse benefit” and “ethics.” These terms encapsulate distinct perspectives on the consequences of actions, the motivations behind them, and the moral frameworks guiding human behavior. This essay aims to delve into the fundamental differences between inverse benefit and ethics, examining their implications for individuals and society at large.

Inverse benefit refers to a scenario where an action intended to bring about positive outcomes inadvertently results in negative consequences. It is characterized by the unintentional, adverse effects of actions or decisions, often stemming from unforeseen circumstances or unintended side effects. This concept underscores the importance of carefully considering the potential repercussions of any given action, as well as the interconnected nature of the choices we make.

In a world shaped by complex systems and dynamic interactions, inverse benefit highlights the inherent challenge of predicting the full spectrum of consequences that may arise from a particular decision. This concept prompts individuals and organizations to adopt a more holistic approach to decision-making, taking into account not only immediate advantages but also potential long-term drawbacks.

Ethics:

Ethics, on the other hand, involves a system of moral principles that guide individuals in distinguishing right from wrong. It serves as a compass for human behavior, providing a framework for evaluating the morality of actions and their impact on individuals and society. Ethical considerations are deeply ingrained in cultural, religious, and philosophical traditions, shaping the norms and values that underpin human interactions.

The study of ethics encompasses various theories, such as deontology, consequentialism, and virtue ethics, each offering distinct perspectives on what constitutes morally right conduct. Deontology, for instance, emphasizes adherence to moral rules and duties, while consequentialism focuses on the outcomes of actions as the basis for ethical judgment. Virtue ethics, in contrast, centers on the development of virtuous character traits to guide ethical decision-making.

Divergence between Inverse Benefit and Ethics:

While both inverse benefit and ethics involve the evaluation of actions and their consequences, they diverge in their focus and underlying principles. Inverse benefit is primarily concerned with unintended negative outcomes resulting from well-intentioned actions, highlighting the need for a comprehensive understanding of the interconnectedness of choices. In contrast, ethics provides a normative framework for determining the morality of actions, emphasizing intentional adherence to moral principles.

The key distinction lies in the proactive versus reactive nature of these concepts. Inverse benefit reacts to the unintended consequences that may emerge after an action, urging individuals to consider the potential downsides before making decisions. Ethics, on the other hand, guides individuals proactively by providing a set of principles to follow, aiming to prevent harmful consequences and promote virtuous conduct from the outset.

Implications for Individuals and Society: Inverse Benefit Law

Inverse Benefit Law, Understanding the difference between inverse benefit and ethics has significant implications for individuals and society. Individuals, when navigating the complexities of decision-making, must be cognizant of the potential unintended consequences of their actions. This awareness encourages a more thoughtful and responsible approach to choices, promoting a consideration of long-term effects beyond immediate gains.

On a societal level, the recognition of inverse benefit underscores the importance of regulatory frameworks and risk assessments in various fields, from technology and medicine to environmental policy. Governments, businesses, and organizations must implement measures to anticipate and mitigate potential negative outcomes, fostering a culture of responsibility and accountability.

In contrast, the ethical principles that guide human behavior play a crucial role in shaping the moral fabric of societies. Ethical considerations influence laws, social norms, and cultural practices, serving as a foundation for trust and cooperation among individuals. A society grounded in ethical values is more likely to foster a sense of justice, equality, and mutual respect.

Inverse benefit and ethics represent distinct but interconnected facets of human decision-making and behavior. Inverse benefit draws attention to the unintended consequences that may arise from actions, prompting a more cautious and thoughtful approach to decision-making. Ethics, on the other hand, provides a proactive moral framework that guides individuals and societies toward intentional and principled conduct.

Both concepts underscore the importance of considering the broader implications of actions, whether in personal, professional, or societal contexts. Striking a balance between an awareness of potential inverse benefits and a commitment to ethical principles can contribute to a more harmonious and responsible coexistence, where individuals and societies navigate the complexities of the human experience with mindfulness and integrity.

How Inverse Benefit affect ethics in terms of pharmaceutical company?

Inverse Benefit Law, the pharmaceutical industry plays a crucial role in global healthcare by researching, developing, and manufacturing drugs that improve and save lives. However, ethical considerations within this industry have been a subject of ongoing debate, and one significant factor that raises ethical concerns is the concept of “inverse benefit.” Inverse benefit refers to situations where the distribution of benefits from pharmaceutical innovations disproportionately favors certain populations or individuals, potentially leading to ethical dilemmas. This essay explores the implications of inverse benefit on ethics within the pharmaceutical industry.

Inverse Benefit Defined:

Inverse benefit in the context of pharmaceuticals can manifest in various ways. It occurs when the distribution of benefits from a drug or medical innovation is not proportional to the distribution of the burden of disease or need. This may result in a scenario where those who need a particular drug the most may not have access to it due to factors such as economic disparities, geographical location, or lack of healthcare infrastructure.

Economic Disparities and Access to Medications: Inverse Benefit Law

Inverse Benefit Law, One of the primary ways inverse benefit affects ethics in the pharmaceutical industry is through economic disparities in access to medications. The high cost of drug development and the need for companies to recoup their investments often lead to pricing strategies that make drugs unaffordable for certain populations. This creates a situation where individuals in lower-income brackets may be unable to access life-saving medications, raising questions about the ethical responsibility of pharmaceutical companies to ensure fair and equitable access.

Geographical Disparities in Clinical Trials:

Clinical trials are a crucial step in bringing new drugs to market, but inverse benefit can be observed in the geographical distribution of these trials. Often, clinical trials are conducted in regions with well-established healthcare infrastructure and regulatory frameworks, leading to a lack of representation from populations in developing countries. This raises ethical concerns as the safety and efficacy of drugs may not be adequately tested across diverse demographic groups, potentially resulting in a lack of access and benefit for those who need it most.

Orphan Drugs and Niche Markets:

Inverse Benefit Law, The development of orphan drugs for rare diseases is another area where inverse benefit can emerge. While these drugs can be life-changing for individuals with rare conditions, their high costs and the limited patient population can make them financially unattractive for pharmaceutical companies. This creates a situation where the benefits of innovation are concentrated in niche markets, leaving individuals with more common ailments underserved. The ethical dilemma lies in balancing the pursuit of profit with the moral obligation to address the healthcare needs of a broader population.

Ethical Considerations and Corporate Social Responsibility:

Addressing inverse benefit in the pharmaceutical industry requires a reevaluation of corporate social responsibility (CSR) and ethical frameworks. Pharmaceutical companies need to prioritize access to essential medications for all individuals, regardless of their economic status or geographical location. Transparency in pricing, increased investment in research for neglected diseases, and global collaboration in clinical trials are steps that can be taken to mitigate the ethical concerns associated with inverse benefit.

Inverse Benefit Law, The concept of inverse benefit challenges the ethical foundations of the pharmaceutical industry, prompting a reassessment of priorities and responsibilities. To uphold ethical standards, pharmaceutical companies must strive for equitable access to medications, address economic and geographical disparities, and prioritize the development of drugs that cater to the broader healthcare needs of the global population. Only through a commitment to ethical practices and corporate social responsibility can the pharmaceutical industry navigate the challenges posed by inverse benefit and contribute to a more just and inclusive healthcare landscape.

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Pharmaceutical Marketing, Balancing Innovation & Ethics

Pharmaceutical marketing serves as the linchpin in the intricate ecosystem of the healthcare industry, functioning as a vital conduit between pharmaceutical entities, healthcare professionals, and patients. Its multifaceted role encompasses a range of crucial activities aimed at introducing, promoting, and facilitating the use of medications. Despite its undeniable significance, the realm of pharmaceutical marketing is not devoid of challenges and controversies, presenting a dynamic landscape that constantly evolves with the ever-changing healthcare landscape.

At its core, pharmaceutical marketing seeks to achieve several key objectives, each contributing to the overall well-being of individuals and the advancement of medical science. One primary goal is the introduction of new medications into the market, a process that involves extensive research, development, and regulatory approvals. Effective marketing strategies play a pivotal role in ensuring that these innovative drugs reach the intended audience and are adopted by healthcare professionals as viable treatment options.

Furthermore, pharmaceutical marketing involves a crucial educational component targeted at healthcare professionals. This aspect is indispensable for fostering an understanding of the latest medical advancements, treatment modalities, and the nuanced characteristics of specific medications. Through comprehensive educational initiatives, pharmaceutical marketers empower healthcare practitioners with the knowledge necessary to make informed decisions about patient care, thereby contributing to improved treatment outcomes.

Beyond the realm of healthcare professionals, pharmaceutical marketing endeavors to create awareness among patients. This involves disseminating information about diseases, available treatment options, and the importance of adhering to prescribed medications. Patient awareness campaigns not only enhance health literacy but also encourage proactive engagement in one’s own healthcare, fostering a collaborative relationship between patients and their healthcare providers.

However, the field of pharmaceutical marketing is not immune to criticism and ethical dilemmas. One of the primary concerns revolves around the ethical considerations of promotional practices employed by pharmaceutical companies. Striking a delicate balance between promoting medications and ensuring that these promotions are based on scientific evidence and genuine medical need is a persistent challenge. The industry has, at times, faced scrutiny for aggressive marketing tactics that may prioritize profit margins over public health.

Pricing issues also loom large in the pharmaceutical marketing landscape. The high cost of certain medications has led to debates about affordability, access to essential drugs, and the economic burden on healthcare systems and patients alike. Striking a balance between recouping research and development costs and ensuring accessibility to life-saving medications for all socio-economic segments remains a complex challenge that requires ongoing dialogue and innovative solutions.

Moreover, the global nature of the pharmaceutical industry introduces additional complexities, with disparities in healthcare infrastructure, regulatory environments, and economic conditions affecting the marketing and distribution of medications on a global scale.

Pharmaceutical marketing is an indispensable component of the healthcare industry, serving as the vital link between innovation and patient care. While it brings life-saving medications to the forefront and facilitates knowledge dissemination, it grapples with ethical considerations, pricing challenges, and the imperative to ensure equitable access to healthcare. Navigating these complexities requires a commitment to ethical standards, transparency, and collaborative efforts among stakeholders to ensure that pharmaceutical marketing continues to evolve in tandem with the evolving needs of society.

Historical Overview

The evolution of pharmaceutical marketing is a fascinating journey that reflects the dynamic intersection of healthcare, technology, and consumer engagement. In the late 19th century, pharmaceutical companies embarked on a paradigm shift by redirecting their promotional efforts towards healthcare professionals. This marked the inception of a trend that would undergo profound transformations over the ensuing decades.

Initially, pharmaceutical marketing revolved around establishing trust and credibility within the medical community. Companies invested heavily in building relationships with physicians, pharmacists, and other healthcare practitioners. The dissemination of product information occurred through direct interactions, medical conferences, and educational materials distributed to medical offices.

As the 20th century unfolded, the pharmaceutical industry witnessed a surge in innovation, not only in drug development but also in marketing strategies. The emergence of mass media, particularly radio and television, opened up new avenues for reaching a wider audience. Companies began to leverage these platforms to communicate directly with consumers, albeit under regulatory constraints.

The turning point, however, came with the advent of the digital age. The rise of the internet and the proliferation of digital platforms transformed the landscape of pharmaceutical marketing. Companies now had the means to disseminate information rapidly and engage with a global audience. Digital marketing strategies, including websites, social media, and online advertisements, became integral components of pharmaceutical promotional campaigns.

Simultaneously, the era of big data and analytics revolutionized how companies understood and approached their target audience. Pharmaceutical marketers started harnessing data to gain insights into consumer behavior, preferences, and trends. This not only improved the efficiency of marketing campaigns but also allowed for more personalized and targeted approaches.

Direct-to-consumer advertising (DTCA) emerged as a significant trend, empowering pharmaceutical companies to communicate directly with patients. Television commercials, online videos, and social media platforms became powerful tools for conveying information about prescription drugs and medical conditions. However, this trend also sparked debates about the ethical implications of promoting prescription medications directly to consumers.

In the 21st century, the evolution of pharmaceutical marketing continues to be shaped by advancements in technology. Artificial intelligence and machine learning are being employed to analyze vast datasets, predict market trends, and optimize marketing strategies. Virtual reality and augmented reality technologies are being explored to enhance medical education and product visualization.

Moreover, the pharmaceutical industry is navigating an era of increased scrutiny and transparency. Stricter regulations, ethical considerations, and demands for clear communication have prompted companies to rethink their marketing practices. Building trust and providing accurate information have become paramount in an age where misinformation can spread rapidly.

The evolution of pharmaceutical marketing is a captivating narrative that spans over a century. From the early focus on healthcare professionals to the digital age of direct-to-consumer advertising, the industry has adapted to changing landscapes while navigating ethical considerations and technological advancements. As the journey continues, the future promises further innovations, challenges, and opportunities in the ever-evolving field of pharmaceutical marketing.

Key Components of Pharmaceutical Marketing

Product Promotion:

The promotion of pharmaceutical products to healthcare professionals is a crucial aspect of the pharmaceutical industry. This practice involves pharmaceutical companies investing significantly in various strategies to inform and persuade healthcare providers about the benefits and uses of their medications. One of the primary methods employed for this purpose is detailing, which encompasses face-to-face promotional visits by pharmaceutical sales representatives to healthcare professionals.

Detailing serves as a direct and personalized approach, allowing representatives to engage in meaningful conversations with healthcare providers. The effectiveness of this strategy hinges on several key factors, with the quality of information being paramount. The representatives must possess in-depth knowledge about the medications they are promoting, including their mechanisms of action, indications, contraindications, potential side effects, and comparisons with alternative treatments. Well-informed representatives are better equipped to address any queries or concerns raised by healthcare professionals, fostering trust and credibility.

Furthermore, the relationship between pharmaceutical sales representatives and healthcare professionals plays a pivotal role in the success of detailing. Building a positive rapport requires effective communication, professionalism, and a genuine commitment to providing valuable information. Establishing a strong relationship often involves regular and consistent interactions over time, allowing the representative to understand the specific needs and preferences of the healthcare professional.

In addition to detailing, pharmaceutical companies utilize various tools and resources to enhance their promotional efforts. These may include educational materials, scientific literature, and digital platforms that offer a wealth of information about the medications. Utilizing technology, such as virtual detailing through video conferencing or online platforms, has become increasingly common, especially in situations where in-person visits may be challenging.

The regulatory environment also plays a significant role in shaping pharmaceutical promotion. Many countries have stringent regulations and guidelines governing the interactions between pharmaceutical representatives and healthcare professionals to ensure ethical practices and the dissemination of accurate information.

Despite the investment in promoting pharmaceutical products, it is essential for the industry to strike a balance between promoting their products and ensuring patient safety. Overemphasis on sales without adequate consideration for patient well-being can lead to ethical concerns. As a result, pharmaceutical companies are increasingly focusing on providing evidence-based information and aligning their promotional activities with the broader goal of improving patient outcomes.

The promotion of pharmaceutical products to healthcare professionals involves a multifaceted approach, with detailing being a key component. The success of this strategy depends on the quality of information provided, the strength of the relationship between the representative and the healthcare professional, adherence to ethical guidelines, and a commitment to improving patient care. As the pharmaceutical landscape continues to evolve, companies must adapt their promotional strategies to align with changing healthcare dynamics and regulatory requirements.

Direct-to-Consumer Advertising (DTCA)

The surge in the direct promotion of prescription drugs to the general public marks a significant shift in pharmaceutical marketing strategies in recent years. Direct-to-consumer advertising (DTCA) has become more prevalent, especially in the United States, where it is legal and has gained widespread acceptance. This approach aims to educate patients about various medical conditions and the treatment options available to them. While the intentions behind DTCA are to empower individuals to take an active role in their healthcare, it also brings forth a range of concerns that warrant careful consideration.

One of the primary goals of DTCA is to inform the public about medical conditions, their symptoms, and potential treatment options. Advocates argue that this increased awareness can lead to early detection of health issues and encourage patients to seek medical advice promptly. By providing information directly to consumers, pharmaceutical companies believe they can contribute to better-informed decisions about healthcare, fostering a more engaged and proactive patient population.

However, the rise of DTCA has sparked a debate about its potential drawbacks. One major concern is the risk of self-diagnosis among consumers who may misinterpret symptoms or believe they require a specific medication without consulting a healthcare professional. This phenomenon could lead to delayed or incorrect treatment, potentially worsening health outcomes. Additionally, the emphasis on specific brand-name drugs in advertisements may steer patients towards more expensive options when equally effective, more affordable alternatives might be available.

Another significant issue arising from DTCA is the potential for an unnecessary demand for specific medications. Patients, influenced by persuasive advertising, may request prescription drugs from their healthcare providers, even if they are not the most suitable option for their medical condition. This can contribute to the overuse of certain medications and the unnecessary strain on healthcare systems.

The United States stands out as one of the few countries where DTCA is legally permitted. In contrast, many other countries, including those in the European Union, have implemented strict regulations prohibiting or heavily restricting the direct advertising of prescription drugs to consumers. Critics argue that the profit-driven nature of pharmaceutical companies in the U.S. may contribute to the persistence of DTCA, potentially prioritizing commercial interests over public health concerns.

To address these issues, proponents of stricter regulations advocate for measures that promote a more balanced approach to drug promotion. This may involve increased scrutiny of the content and claims made in advertisements, along with educational campaigns to help consumers critically evaluate the information presented. Striking a balance between empowering patients with knowledge and safeguarding against the risks associated with self-diagnosis and unnecessary demand for specific medications is crucial for maintaining the integrity of healthcare systems in the face of evolving marketing practices.

Digital Marketing

The advent of the internet has revolutionized the way industries operate, and the pharmaceutical sector is no exception. In response to the digital era, pharmaceutical companies have strategically embraced a variety of digital marketing strategies, recognizing the immense potential for reaching a broader audience and fostering meaningful connections with healthcare professionals and patients alike.

One of the primary components of this digital transformation is online advertising. Pharmaceutical companies are leveraging targeted online ads to effectively reach specific demographics, ensuring that their messages reach the right audience. These advertisements may encompass a range of formats, from display ads on relevant websites to sponsored content in healthcare publications, allowing companies to promote their products and disseminate important information in a visually engaging manner.

Social media campaigns have become another cornerstone of digital marketing in the pharmaceutical industry. Platforms such as Facebook, Twitter, LinkedIn, and Instagram offer a unique opportunity to connect with diverse audiences. Pharmaceutical companies use these platforms not only to showcase their products but also to engage in conversations, share educational content, and participate in relevant healthcare discussions. Social media provides a dynamic space for disseminating information rapidly and building a community around specific healthcare topics.

Content marketing has also emerged as a crucial element of pharmaceutical digital strategies. Companies are creating and sharing informative content, ranging from blog posts and articles to infographics and videos. By providing valuable and educational content, pharmaceutical companies position themselves as authorities in their respective therapeutic areas, building trust and credibility among healthcare professionals and patients. This approach not only fosters brand awareness but also contributes to the overall knowledge and understanding of healthcare issues.

Digital platforms offer an interactive and dynamic way to engage healthcare professionals. Online portals and platforms enable pharmaceutical companies to provide comprehensive resources, such as research studies, clinical trial information, and product details. This digital interaction allows healthcare professionals to stay informed about the latest advancements, facilitating evidence-based decision-making in their practices.

Similarly, patients benefit from the accessibility of information provided through digital channels. Pharmaceutical companies can create patient-centric content, addressing common concerns, providing information about diseases and treatment options, and promoting general health and wellness. Interactive tools, such as symptom checkers or dosage calculators, can enhance the overall patient experience and empower individuals to take a more active role in their healthcare.

The integration of digital marketing strategies into the pharmaceutical industry has opened up new avenues for communication, education, and engagement. The internet’s dynamic and interactive nature enables pharmaceutical companies to connect with healthcare professionals and patients in ways that were not possible before. As technology continues to evolve, the role of digital marketing in the pharmaceutical sector is likely to expand further, driving innovation and improving overall healthcare outcomes.

Conferences and Sponsorships

The participation of pharmaceutical companies in medical conferences serves as a strategic and multifaceted approach to connect with the healthcare industry and promote their latest innovations. Beyond a simple marketing endeavor, this engagement plays a pivotal role in fostering collaboration, disseminating knowledge, and staying at the forefront of medical advancements. Here’s an expanded exploration of this concept-

Medical conferences provide a dynamic platform for pharmaceutical companies to share their cutting-edge research, breakthrough therapies, and innovative products with healthcare professionals. By presenting their work, these companies contribute to the collective knowledge of the medical community, fostering an environment of continuous learning and discovery.

Participation in medical conferences enhances the scientific credibility of pharmaceutical companies. Presenting research findings, clinical trial outcomes, and technological advancements in a peer-reviewed setting establishes the legitimacy of their innovations. This scientific validation is crucial for gaining the trust of healthcare professionals and the broader medical community.

Conferences offer unparalleled opportunities for networking and relationship-building. Pharmaceutical representatives can interact directly with healthcare professionals, including physicians, researchers, and key opinion leaders. These relationships are instrumental in establishing a two-way dialogue, enabling companies to better understand the needs of the medical community and tailor their innovations accordingly.

Engaging in medical conferences allows pharmaceutical companies to receive real-time feedback on their products and innovations. Direct interactions with healthcare professionals offer valuable insights into the practical applications, challenges, and potential improvements for their offerings. This feedback loop is instrumental in refining products and ensuring they meet the evolving needs of the medical field.

Beyond showcasing their products, pharmaceutical companies often organize educational sessions, workshops, and symposiums during conferences. These initiatives aim to educate healthcare professionals about the latest therapeutic approaches, medical technologies, and treatment protocols. By contributing to the educational component of the conference, companies position themselves as thought leaders in the industry.

Participation in medical conferences provides pharmaceutical companies with a platform for increased visibility. Booths, sponsored events, and branded materials help create a strong presence, ensuring that their innovations are noticed by a diverse audience. This visibility extends beyond the conference as attendees share insights and experiences with their peers.

Medical conferences serve as forums for discussing and disseminating updates on regulatory frameworks and compliance standards. For pharmaceutical companies, staying informed about these changes is crucial to ensure that their innovations adhere to the latest guidelines. Conferences provide an opportunity for companies to showcase their commitment to ethical practices and regulatory compliance.

Attending medical conferences allows pharmaceutical companies to stay abreast of emerging trends in healthcare and the pharmaceutical industry. It also provides a platform for analyzing the strategies of competitors, understanding market dynamics, and adapting their own approaches to remain competitive.

Pharmaceutical companies’ participation in medical conferences goes beyond traditional marketing; it is a strategic investment in building relationships, fostering scientific credibility, and contributing to the advancement of medical knowledge and practice. Through these engagements, companies position themselves as integral partners in the collaborative effort to improve patient outcomes and advance the field of healthcare.

Challenges and Ethical Concerns

Ethical Dilemmas

Pharmaceutical marketing operates within a complex landscape where the pursuit of profit often intersects with the imperative to uphold ethical standards. One prominent ethical challenge is the promotion of off-label drug uses, wherein pharmaceutical companies market a drug for uses that have not been approved by regulatory authorities. This practice raises concerns about patient safety, as the efficacy and safety of a drug may not be adequately studied for these off-label uses.

Biased information dissemination is another critical ethical concern within pharmaceutical marketing. Companies may selectively present data that highlights the positive aspects of their products while downplaying potential risks or side effects. This can lead to a distorted perception of a drug’s benefits and risks among healthcare professionals and the public, potentially compromising patient safety and informed decision-making.

Financial incentives also play a significant role in shaping prescribing behavior, as healthcare professionals may be influenced by perks, gifts, or payments from pharmaceutical companies. This can create conflicts of interest, raising questions about the objectivity of medical recommendations and potentially compromising the well-being of patients. Striking a balance between the legitimate promotion of pharmaceutical products and ensuring that financial incentives do not unduly influence medical decisions is a delicate ethical challenge that requires constant vigilance.

The digital age has introduced new dimensions to these challenges, with online platforms and social media becoming powerful tools for pharmaceutical marketing. This raises concerns about the responsible use of digital channels, as misinformation and biased content can spread rapidly, influencing healthcare professionals and the general public. Pharmaceutical companies must navigate these digital spaces ethically, ensuring that their marketing practices adhere to the highest standards of accuracy, transparency, and patient welfare.

Regulatory bodies play a crucial role in addressing these ethical challenges, with the need for robust oversight and enforcement of guidelines to ensure that pharmaceutical marketing practices align with ethical standards. Additionally, fostering a culture of transparency within the industry, where companies willingly disclose information about their marketing strategies and financial relationships with healthcare professionals, can contribute to building trust and accountability.

Ultimately, the ethical challenges in pharmaceutical marketing underscore the need for a holistic approach that involves collaboration between industry stakeholders, healthcare professionals, regulatory bodies, and the public. By fostering an environment that prioritizes patient welfare, transparency, and the dissemination of accurate information, the pharmaceutical industry can navigate these challenges and contribute to the advancement of ethical standards in healthcare.

Access and Affordability

The high cost of pharmaceuticals is a pervasive global concern that has far-reaching implications for individuals, healthcare systems, and societies at large. One of the key factors contributing to the escalating prices of medications is the intricate web of marketing practices employed by pharmaceutical companies. While these practices are essential for promoting and distributing drugs, they also play a significant role in driving up overall costs.

Pharmaceutical companies invest substantial resources in research and development to bring new and innovative medications to the market. These investments are often colossal, involving extensive clinical trials, regulatory approvals, and continuous monitoring for safety and efficacy. To recoup these significant expenditures, companies resort to pricing strategies that not only cover the development costs but also generate profits.

The marketing practices adopted by pharmaceutical companies add an additional layer to the cost conundrum. Aggressive advertising campaigns, direct-to-consumer marketing, and other promotional efforts contribute to the overall expense associated with a particular drug. In an attempt to establish brand recognition and gain a competitive edge, companies allocate substantial budgets to marketing, which, in turn, impact the final price of the medications.

This situation raises critical questions about the accessibility and affordability of essential medications, especially those that are life-saving. The exorbitant costs create barriers for patients, limiting their ability to afford necessary treatments. This challenge is particularly pronounced in the case of chronic conditions and rare diseases, where ongoing medication is crucial for maintaining health and well-being.

The global implications of high pharmaceutical costs extend beyond individual struggles. Healthcare systems worldwide face the burden of budget constraints, as the costs of medications strain available resources. Governments, insurers, and healthcare providers grapple with the ethical dilemma of balancing the need for innovative treatments with the necessity of providing affordable healthcare for their populations.

Efforts to address these challenges involve a multifaceted approach. Policymakers must explore strategies to encourage competition in the pharmaceutical industry, promote transparency in pricing, and support the development of generic alternatives. Additionally, there is a growing call for increased collaboration between governments, pharmaceutical companies, and healthcare stakeholders to find sustainable solutions that prioritize both innovation and affordability.

The high cost of pharmaceuticals, exacerbated by marketing practices aimed at recouping research and development expenses, raises profound concerns about accessibility and affordability. Striking a balance between incentivizing innovation and ensuring equitable access to life-saving medications is crucial for the well-being of individuals and the sustainability of healthcare systems worldwide. Addressing this complex issue requires coordinated efforts from policymakers, industry leaders, and healthcare advocates to create a healthcare landscape that is both innovative and accessible to all.

Regulatory Compliance

Governments and regulatory bodies worldwide play a pivotal role in overseeing and regulating pharmaceutical marketing practices, recognizing the profound impact these practices can have on public health and the healthcare industry. The implementation of stringent regulations serves as a fundamental mechanism to ensure the reliability, accuracy, and ethical standards of information disseminated by pharmaceutical companies. This regulatory framework is designed to prevent misleading claims, safeguard the well-being of patients, and maintain transparency in the relationships between pharmaceutical entities and healthcare professionals.

One of the primary objectives of these regulations is to guarantee the accuracy of information provided by pharmaceutical companies in their marketing materials. Ensuring that promotional content accurately represents the benefits, risks, and limitations of a given medication is crucial for healthcare professionals and, more importantly, for the patients who rely on these medications for their health and well-being. Regulatory bodies set clear guidelines regarding the scientific evidence required to support marketing claims, fostering evidence-based medicine and informed decision-making within the medical community.

Preventing misleading claims is another key focus of pharmaceutical marketing regulations. Misleading advertisements or promotional materials can potentially lead to inappropriate prescription practices, misinformed patients, and, ultimately, jeopardize public health. Regulatory bodies work to establish and enforce standards that prohibit deceptive marketing practices, such as false efficacy claims, unsupported superiority assertions, or the omission of critical safety information. By doing so, they contribute to the creation of a more trustworthy and responsible pharmaceutical marketing environment.

Transparency in interactions between pharmaceutical companies and healthcare professionals is an essential aspect of maintaining public trust and ensuring ethical practices within the industry. Regulatory bodies often mandate disclosure requirements for financial relationships and collaborations between pharmaceutical companies and healthcare professionals. These requirements aim to minimize the potential influence of commercial interests on medical decision-making, promoting objectivity in the prescription and use of pharmaceutical products.
In addition to monitoring the content of marketing materials, regulatory bodies may also oversee the channels through which pharmaceutical companies promote their products. This includes digital marketing, social media, and other platforms where information is disseminated to healthcare professionals and the general public. By adapting regulations to the evolving landscape of communication, regulatory bodies can address emerging challenges and technologies to maintain the integrity of pharmaceutical marketing practices.

Overall, the role of governments and regulatory bodies in monitoring and regulating pharmaceutical marketing practices is instrumental in upholding the principles of patient safety, public health, and ethical conduct within the healthcare industry. Stringent regulations act as a safeguard, promoting accountability, transparency, and responsible behavior among pharmaceutical companies, ultimately contributing to a healthcare landscape that prioritizes the well-being of individuals and communities.

Here is a table illustrating the top pharmaceutical companies based on global revenue

RankCompanyRevenue (USD Billion)Headquarters
1Pfizer$81.43New York, USA
2Roche$61.72Basel, Switzerland
3Johnson & Johnson$56.10New Jersey, USA
4Novartis$51.90Basel, Switzerland
5Merck & Co.$48.05New Jersey, USA

Example: Pfizer’s revenue reflects its strong presence in the pharmaceutical market, driven by blockbuster drugs like Lipitor and Viagra

Overall, the realm of pharmaceutical marketing is intricate and multifaceted, exerting a profound influence on the healthcare landscape through diverse channels. Achieving a delicate equilibrium between the imperatives of innovation, ethical considerations, and widespread accessibility stands as a pivotal requirement for fostering sustainable growth within the industry. It is imperative for the pharmaceutical sector to navigate a landscape marked by stringent regulations, uphold transparent practices, and steadfastly direct efforts towards addressing global health imperatives. This concerted approach is indispensable to guarantee that pharmaceutical marketing not only aligns with the interests of healthcare professionals but also prioritizes the well-being of patients on a global scale. By embracing a commitment to ethical conduct, stringent regulatory oversight, and a comprehensive focus on addressing global health challenges, the pharmaceutical industry can amplify its positive impact and contribute meaningfully to the advancement of healthcare for all.

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Pharmaceutical Lobby, Navigating Healthcare & Industry Influence

Pharmaceutical Lobby

Pharmaceutical lobby, a powerful force within the realm of healthcare policy and regulation, plays a significant role in shaping the landscape of the pharmaceutical industry. Comprising a network of advocacy groups, trade associations, and individual corporations, the lobby exerts influence through various channels, including political contributions, lobbying efforts, and strategic alliances. This essay delves into the dynamics of the pharmaceutical lobby, examining its impact on healthcare policies, regulatory decisions, and public perception.

[I] Overview of the Pharmaceutical Lobby:

Pharmaceutical lobby is a collective term for organizations that represent the interests of pharmaceutical companies. These organizations aim to influence lawmakers, regulators, and policymakers to shape legislation and regulations that favor the industry. Major players in the pharmaceutical lobby include the Pharmaceutical Research and Manufacturers of America (PhRMA), Biotechnology Innovation Organization (BIO), and the Generic Pharmaceutical Association (GPhA).

[II] Lobbying Strategies and Tactics:

1. Political Contributions:

One of the primary tools employed by the pharmaceutical lobby is political contributions. Through Political Action Committees (PACs) and direct donations, pharmaceutical companies fund political campaigns, supporting candidates who are aligned with their interests. This financial support often translates into increased access to policymakers and a favorable stance on industry-related issues.

YearTotal Pharmaceutical Lobby Contributions (in millions)
2020$335
2019$283
2018$281

2. Lobbying Expenditures:

Lobbying expenditures stand as a pivotal facet in illustrating the considerable impact wielded by the pharmaceutical lobby. These financial allocations encompass a spectrum of activities, ranging from the recruitment of lobbyists to the execution of comprehensive advocacy campaigns, all aimed at shaping and molding legislative decisions in favor of the pharmaceutical industry. In essence, these expenditures encapsulate the multifaceted strategies employed by the pharmaceutical lobby to assert its influence on the political landscape, emphasizing the complex interplay of financial resources, strategic advocacy, and legislative impact within this influential sector.

YearTotal Pharmaceutical Lobby Expenditures (in millions)
2020$306
2019$295
2018$283

[III] Impact on Healthcare Policies:

1. Policy Advocacy:

Pharmaceutical lobby takes an assertive stance in promoting policies that are in harmony with the objectives of the industry. This involves not only advocating for the safeguarding of intellectual property rights but also championing initiatives to simplify regulatory procedures. Additionally, the lobby strives to cultivate an atmosphere that nurtures innovation, aiming to create an environment where advancements in pharmaceuticals can thrive.

2. Drug Pricing Legislation:

Pharmaceutical lobby has played a crucial role in shaping conversations concerning drug pricing. The industry’s lobbying endeavors have concentrated on actively influencing legislative measures pertaining to the control mechanisms of drug pricing and reimbursement policies. These concerted efforts underscore the lobby’s substantial impact on advocating for changes and reforms within the pharmaceutical landscape.

YearNotable Drug Pricing Legislation
2019H.R. 3 - Lower Drug Costs Now Act (aimed at reducing drug prices)
2020Executive Order on "Most-Favored-Nation" Drug Pricing
2021The Elijah E. Cummings Lower Drug Costs Now Act

[IV] Regulatory Capture and Criticisms:

1. Regulatory Influence:

Critics contend that the pharmaceutical lobby’s impact reaches beyond legislative realms and permeates regulatory bodies as well. The elevation of former industry executives to pivotal regulatory roles has sparked apprehension regarding the prospect of regulatory capture. This phenomenon suggests that agencies entrusted with safeguarding public health might shift their focus and priorities to be more in sync with the interests of the pharmaceutical industry, potentially compromising their primary mission of ensuring the well-being of the general populace.

2. Criticism of High Drug Prices:

The lobby is under intense public and political scrutiny, particularly concerning the exorbitant costs associated with prescription drugs. Detractors contend that the pharmaceutical industry’s considerable influence has played a significant role in impeding the implementation of effective measures to regulate and decrease drug prices. This influence, they argue, has created a situation where patients face challenges in accessing crucial medications due to the financial burden imposed by high drug prices. In essence, the pharmaceutical lobby’s impact on drug pricing has become a focal point of concern, with critics emphasizing the negative repercussions it has on the broader healthcare landscape and the well-being of individuals reliant on these essential medications.

[IV] Public Perception and Reform Efforts:

1. Public Awareness:

Growing public awareness regarding the activities of the pharmaceutical lobby has prompted a heightened scrutiny of its impact on the formulation of healthcare policies. This increased awareness has sparked conversations about the imperative for transparency, accountability, and comprehensive reforms to counteract any unwarranted influence on the policymaking process. The acknowledgment of these issues underscores a collective call for a more transparent and accountable healthcare landscape, where the interests of the public are prioritized over undue external pressures.

2. Reform Efforts:

Proposals to tackle issues associated with the influence of the pharmaceutical lobby encompass a range of strategies, such as advocating for changes in campaign finance regulations, enhancing transparency in lobbying endeavors, and implementing safeguards to curb regulatory capture. These reform initiatives are designed to find a nuanced equilibrium between promoting innovation within the pharmaceutical industry and guaranteeing that essential medications remain accessible and affordable to the broader population. By targeting various facets of the lobbying landscape, these proposals seek to create a more transparent, accountable, and balanced framework that prioritizes the public’s health and well-being while encouraging advancements in pharmaceutical research and development.

The intricate and multifaceted influence wielded by the pharmaceutical lobby constitutes a nuanced element within the broader healthcare panorama. In the ongoing evolution of the industry, the intricate dance between pharmaceutical interests and the imperatives of public health emerges as a focal point for continuous scrutiny and debate. Navigating this intricate terrain involves a delicate equilibrium – one that demands policymakers, healthcare professionals, and the public to grapple with the intricate challenge of fostering innovation while concurrently safeguarding equitable access to healthcare. This perpetual balancing act is crucial in steering towards a future that is both healthier and more sustainable.

Is Pharmaceutical Lobby Affect Drug Quality?

The influence exerted by pharmaceutical lobbying on drug quality is a multifaceted and contentious subject warranting a nuanced examination. Within the intricately regulated pharmaceutical industry, the assurance of drug quality stands as a paramount concern, inextricably linked to patient safety and therapeutic efficacy. Regulatory entities such as the U.S. Food and Drug Administration (FDA) and their global counterparts play an indispensable role in promulgating and upholding standards, conducting inspections, and ensuring that pharmaceutical products adhere to stringent criteria encompassing quality, safety, and efficacy.

Despite the pivotal role of regulatory agencies, apprehensions persist concerning the potential sway of pharmaceutical lobbying on pivotal processes such as the formulation of regulations, shaping of policies, and enforcement. Detractors posit that the extensive lobbying undertaken by pharmaceutical entities may culminate in regulations that lean favorably towards industry interests, potentially compromising the rigorous nature of safety and quality standards. This influence could manifest in various ways, such as impacting the drug approval process, expediting reviews, or affecting the depth of post-marketing surveillance.

It is imperative to acknowledge the substantial contributions of the pharmaceutical sector to research and development, ushering in novel and groundbreaking drugs to the market. Striking a delicate balance between promoting innovation and ensuring patient safety is at the core of ongoing discussions surrounding the influence of lobbying.

In recent years, concerted efforts have been made to augment transparency and mitigate potential conflicts of interest in regulatory processes. Regulatory agencies are steadfastly committed to preserving public trust by basing decisions on scientific evidence and prioritizing public health interests. However, the interplay between the pharmaceutical industry and regulatory bodies remains under intense scrutiny and continues to be a focal point of discussion.

Ultimately, the impact of pharmaceutical lobbying on drug quality is not uniform and is contingent upon several factors, including the robustness of regulatory frameworks, the effectiveness of transparency measures, and the dedication of regulatory agencies to upholding stringent standards. Public awareness, advocacy initiatives, and ongoing scrutiny emerge as indispensable elements in holding both the pharmaceutical industry and regulatory bodies accountable for ensuring the highest standards of drug quality and safety. The perpetual dialogue surrounding this issue underscores the importance of maintaining a delicate equilibrium between fostering innovation and safeguarding public health.

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Ethics in Pharmaceutical Sales :Striking a Balance Between Business and Patient Welfare

Ethics in Pharmaceutical Sales

Ethics in Pharmaceutical Sales, Pharmaceutical sales constitute a pivotal function within the healthcare sector, serving as a critical link between the production of medications and their accessibility to patients. The significance of this role lies in its ability to facilitate the dissemination of essential treatments, ensuring they reach individuals in need. Despite its inherent importance, the pharmaceutical sales domain is not impervious to ethical dilemmas. The pursuit of revenue goals and a competitive advantage by pharmaceutical companies introduces a nuanced dimension to the ethical considerations associated with sales practices.

In the pharmaceutical industry, where profitability and market competitiveness are paramount, the ethical facets of sales strategies often face scrutiny. This essay delves into the intricate landscape of ethics within pharmaceutical sales, seeking to unravel the multifaceted dynamics that govern this field. Emphasizing the delicate equilibrium required between business objectives and the fundamental well-being of patients, it explores the ethical challenges that arise when companies navigate the intricate intersection of commerce and healthcare. The exploration encompasses the ethical dilemmas posed by marketing tactics, pricing strategies, and interactions with healthcare professionals, highlighting the intricate ethical framework that must be navigated to uphold both corporate success and patient welfare.

The Pharmaceutical Sales Environment

In the realm of pharmaceuticals, the process of selling involves the dynamic promotion and distribution of medications to healthcare professionals and institutions. At the forefront of this intricate ecosystem are sales representatives, commonly known as medical or pharmaceutical representatives, who assume a pivotal role in conveying comprehensive information about newly developed drugs. This information includes insights into the drugs’ advantages, as well as guidelines pertaining to their usage.

The pharmaceutical industry is characterized by intense competition, as companies vigorously strive to secure a substantial market share and ensure profitability. The competitive landscape necessitates adept navigation of regulatory frameworks, understanding the nuances of medical science, and cultivating strong relationships with healthcare stakeholders. Sales representatives, acting as the linchpin between pharmaceutical companies and the healthcare community, are tasked with the responsibility of not only promoting products but also staying abreast of scientific advancements and industry trends.

Furthermore, the pharmaceutical sales process involves navigating a complex web of regulations and compliance standards, given the stringent oversight governing the development, manufacturing, and marketing of pharmaceutical products. Sales representatives are required to demonstrate a profound understanding of these regulations to ensure that their promotional activities align with industry guidelines and ethical standards.

In essence, pharmaceutical sales is a multifaceted endeavor that extends beyond the mere exchange of products. It encompasses a strategic interplay of information dissemination, relationship-building, regulatory compliance, and adaptation to the ever-evolving landscape of medical science and market dynamics. Successful engagement in pharmaceutical sales demands a nuanced approach that goes beyond traditional selling tactics, requiring a deep understanding of both the scientific and business facets of the industry.

Key Players in the Pharmaceutical Industry

CompanyMarket Capitalization (USD)Revenue (2022, USD)Key Products
Pfizer Inc.$250 billion$85.6 billionLipitor, Viagra, Prevnar, Xeljanz
Roche Holding AG$302 billion$68.1 billionRituxan, Avastin, Herceptin, Tamiflu
Johnson & Johnson$488 billion$93.8 billionRemicade, Imbruvica, Stelara, Zytiga
Novartis International$229 billion$53.7 billionGilenya, Lucentis, Cosentyx, Diovan
Merck & Co. Inc.$204 billion$47.7 billionKeytruda, Gardasil, Januvia, Propecia

Ethical Challenges in Pharmaceutical Sales

Off-Label Marketing

Ethics in Pharmaceutical Sales, A significant ethical dilemma within the realm of pharmaceutical sales revolves around the issue of off-label marketing. This ethical concern arises when pharmaceutical companies engage in the promotion of a drug for purposes that have not been officially sanctioned by regulatory authorities. Off-label use refers to the prescription of a medication for conditions or patient populations that fall outside the scope of its approved indications.

While healthcare providers are permitted to exercise their discretion and prescribe drugs for off-label purposes based on their clinical judgment and expertise, pharmaceutical companies are obligated to operate within stringent guidelines when it comes to promoting their products. The ethical tension arises from the potential divergence between the legitimate medical needs of patients and the commercial interests of pharmaceutical firms.

The practice of off-label marketing raises several ethical considerations. First and foremost, there is a concern about patient safety and well-being. When drugs are promoted for uses that have not been rigorously evaluated and approved by regulatory bodies, there is an inherent risk of exposing patients to unanticipated side effects or ineffective treatments. This misalignment between commercial interests and patient welfare underscores the ethical imperative for pharmaceutical companies to prioritize accurate and transparent communication about the approved uses of their products.

Furthermore, off-label marketing can erode the trust between healthcare providers and pharmaceutical companies, as it may create a perception that commercial interests are taking precedence over scientific evidence and patient safety. This erosion of trust has broader implications for the healthcare ecosystem, affecting the collaborative efforts between medical professionals and the pharmaceutical industry in advancing healthcare solutions.

To address these ethical concerns, regulatory bodies play a pivotal role in overseeing and enforcing guidelines that govern the promotion of pharmaceutical products. Companies must navigate a delicate balance between promoting their products to healthcare professionals for approved uses and avoiding the temptation to overstep ethical boundaries by encouraging off-label uses without robust scientific support.

In summary, the ethical challenges associated with off-label marketing in pharmaceutical sales revolve around the tension between the legitimate medical needs of patients and the commercial interests of pharmaceutical companies. Striking the right balance requires a commitment to transparency, adherence to regulatory guidelines, and a focus on prioritizing patient welfare over profit motives.

Notable Cases of Off-Label Marketing

CompanyDrugOff-Label UseLegal Consequences
Pfizer Inc.NeurontinBipolar disorder, migraines, and neuropathic pain$430 million settlement in 2004
Johnson & JohnsonRisperdalDementia in elderly patients$2.2 billion settlement in 2013
Eli Lilly and CompanyZyprexaDementia and mood disorders$1.42 billion settlement in 2009
AstraZenecaSeroquelAggression, Alzheimer's, PTSD$520 million settlement in 2010

Incentives and Gifts to Healthcare Professionals

Ethics in Pharmaceutical Sales, Pharmaceutical companies frequently offer incentives, gifts, or sponsorships to healthcare professionals as a means to promote the utilization of their pharmaceutical products. Although these practices may fall within legal boundaries, they give rise to ethical apprehensions regarding their potential impact on the impartiality of medical decision-making.

The relationship between pharmaceutical companies and healthcare professionals is intricate and multifaceted. In an attempt to enhance brand awareness and increase product visibility, pharmaceutical companies may extend various perks to healthcare professionals, including financial incentives, gifts, or financial support for educational events and conferences. While such initiatives are not inherently illegal, they do invite scrutiny due to the potential influence they may exert on healthcare professionals’ prescribing practices.

The concern lies in the potential conflict of interest that may arise when healthcare professionals receive these inducements. The fear is that these incentives could compromise the objectivity of medical decision-making, leading healthcare professionals to prioritize certain drugs over others based on factors beyond their therapeutic efficacy. This scenario poses ethical challenges as it may undermine the fundamental principle of patient-centered care, where treatment decisions should be solely guided by the best interests of the patient.

To address these ethical concerns, there have been ongoing efforts to establish and enforce guidelines and regulations that govern the interactions between pharmaceutical companies and healthcare professionals. These measures aim to promote transparency, limit the extent of financial relationships, and ensure that medical decisions remain grounded in evidence-based practices rather than influenced by external incentives.

In summary, while the practices of providing incentives, gifts, or sponsorships by pharmaceutical companies to healthcare professionals are legally permissible to a certain extent, the ethical implications surrounding these interactions necessitate careful consideration. The ongoing discourse on this issue underscores the importance of maintaining the integrity of medical decision-making to safeguard the trust and well-being of patients.

Examples of Pharmaceutical Company Payments to Healthcare Professionals

CompanyPayments (USD)Purpose of PaymentsNotable Cases
Novartis International$112 million (2019)Speaker fees, meals, and travel expensesSettlement in a 2015 lawsuit
Johnson & Johnson$2.7 million (2021)Speaker fees and consulting paymentsSettlement with the DOJ in 2019
GlaxoSmithKline$3 billion (2012)Kickbacks, false claims, and off-label promotionOne of the largest healthcare fraud settlements

Patient Privacy and Data Security

Ethics in Pharmaceutical Sales, The growing adoption of digital technologies in the field of pharmaceutical sales has given rise to apprehensions regarding the safeguarding of patient privacy and ensuring the security of sensitive data. As pharmaceutical companies delve into the realm of digitalization, they find themselves confronted with a complex ethical landscape, particularly concerning the acquisition, retention, and utilization of patient data for marketing endeavors.

In this context, the ethical challenges manifest in various stages of the data lifecycle, commencing with the collection process. Companies need to grapple with questions surrounding the transparency and consent mechanisms employed when gathering patient information. Transparency ensures that patients are adequately informed about the data being collected, the purposes for which it will be used, and any potential implications. Obtaining informed consent becomes pivotal in respecting the autonomy and privacy rights of individuals, as it empowers them to make informed decisions regarding the use of their data.

Moving forward, the storage of patient data demands a robust infrastructure that not only safeguards against unauthorized access but also ensures the integrity and confidentiality of the information. The implementation of stringent security measures becomes imperative to thwart potential breaches that could compromise patient confidentiality. This involves employing encryption protocols, access controls, and regular audits to monitor and fortify the security apparatus.

Moreover, the ethical considerations extend to the subsequent use of patient data for marketing endeavors. Striking a balance between leveraging data to enhance pharmaceutical sales and respecting patient privacy requires a delicate approach. Companies must prioritize responsible data usage, ensuring that marketing strategies are ethically aligned with the expectations and preferences of patients. This involves avoiding intrusive practices, respecting opt-out preferences, and refraining from exploiting sensitive health information for commercial gains.

Moreover, the ethical considerations extend to the subsequent use of patient data for marketing endeavors. Striking a balance between leveraging data to enhance pharmaceutical sales and respecting patient privacy requires a delicate approach. Companies must prioritize responsible data usage, ensuring that marketing strategies are ethically aligned with the expectations and preferences of patients. This involves avoiding intrusive practices, respecting opt-out preferences, and refraining from exploiting sensitive health information for commercial gains.

In essence, the integration of digital technologies in pharmaceutical sales necessitates a conscientious approach by companies, where ethical considerations surrounding patient data take center stage. By implementing transparent data collection practices, fortifying data security measures, and adhering to ethical marketing principles, pharmaceutical companies can navigate the challenges posed by the digital era while upholding the trust and privacy of the individuals they serve.

Data Breaches in Pharmaceutical Companies

CompanyDate of BreachNature of BreachConsequences
Pfizer Inc.2020Unauthorized access to customer dataFines and reputational damage
AstraZeneca2018Insider breach resulting in data theftInvestigations and enhanced security measures
Merck & Co. Inc.2017Petya ransomware attackDisruption of operations and financial losses

Ethical Frameworks and Solutions

Ethics in Pharmaceutical Sales, Tackling ethical dilemmas within the realm of pharmaceutical sales necessitates the implementation of comprehensive ethical frameworks and the development of solutions that span the entire industry. This involves fostering a collaborative effort among regulatory bodies, healthcare professionals, and pharmaceutical companies to not only define but also rigorously enforce ethical standards.

To delve deeper into this concept, it is crucial to understand that ethical challenges in pharmaceutical sales can encompass a wide range of issues, such as marketing practices, interactions with healthcare providers, drug pricing, and the transparency of clinical trial data. Robust ethical frameworks serve as guiding principles that help navigate these complex issues by providing a set of values and standards that uphold the integrity of the industry.

The involvement of regulatory bodies is instrumental in ensuring that these ethical frameworks are not just aspirational but are also legally binding. These bodies play a key role in formulating and updating regulations that govern pharmaceutical sales, ensuring that they align with evolving ethical considerations and maintain public trust.

Collaboration with healthcare professionals is equally vital, as they are at the frontline of patient care and can provide valuable insights into the impact of pharmaceutical sales practices on patient well-being. Establishing open lines of communication between pharmaceutical companies and healthcare professionals fosters a relationship built on transparency and mutual understanding, reducing the potential for conflicts of interest and unethical behavior.

Moreover, pharmaceutical companies themselves play a pivotal role in driving ethical practices within the industry. This involves not only adhering to established ethical standards but also actively engaging in initiatives that promote transparency, fair pricing, and responsible marketing.

In summary, addressing ethical challenges in pharmaceutical sales is a multifaceted endeavor that requires a concerted effort from regulatory bodies, healthcare professionals, and pharmaceutical companies. The adoption of robust ethical frameworks serves as a foundation for establishing and maintaining industry-wide ethical standards, ensuring the integrity of pharmaceutical sales and, ultimately, safeguarding the well-being of patients.

Compliance with Regulations

Ethics in Pharmaceutical Sales, Pharmaceutical companies are obligated to meticulously comply with the regulatory frameworks established by government agencies, such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). This stringent adherence encompasses a multifaceted commitment to guaranteeing that all promotional endeavors are in strict accordance with the approved uses of their products. Additionally, companies must uphold transparency and legality in their financial relationships with healthcare professionals.

The regulatory landscape governing pharmaceutical activities serves as a safeguard to protect public health and ensure the integrity of the healthcare system. The U.S. FDA and the European Medicines Agency, among other regulatory bodies globally, set forth guidelines and standards that pharmaceutical companies must follow to ensure the safety, efficacy, and quality of their products.

One critical aspect of adherence to regulations involves promotional practices. Pharmaceutical companies must ensure that their promotional materials, whether aimed at healthcare professionals or the general public, accurately reflect the approved uses and indications of their drugs. This helps prevent misinformation and ensures that healthcare providers and consumers have reliable and truthful information about the products.

Furthermore, the financial relationships between pharmaceutical companies and healthcare professionals must be characterized by transparency and legality. This is to avoid conflicts of interest and any potential influence that may compromise the objectivity of healthcare professionals in their clinical decision-making processes. Disclosing financial ties and maintaining ethical interactions with healthcare professionals contribute to the overall credibility and trustworthiness of the pharmaceutical industry.

In summary, the strict adherence to regulations established by government agencies is integral to the pharmaceutical industry’s ethical conduct. By aligning promotional activities with approved uses and maintaining transparent and lawful financial relationships, pharmaceutical companies contribute to building a foundation of trust, ensuring patient safety, and upholding the integrity of the healthcare system.

Training and Education

Ethics in Pharmaceutical Sales, Sales representatives must receive thorough training in ethical guidelines and compliance standards to ensure a deep understanding of the principles governing their conduct. This training is crucial for instilling a strong awareness of the significance of promoting pharmaceutical products based on rigorous scientific evidence and within the confines of regulatory approvals.

The comprehensive training program should cover various aspects, including but not limited to, ethical considerations, legal obligations, and industry-specific guidelines. Sales representatives need to be well-versed in the ethical principles that govern their interactions with healthcare professionals, ensuring that their promotional activities prioritize transparency, honesty, and integrity.

Furthermore, the training should underscore the importance of aligning promotional efforts with scientifically substantiated information. Sales representatives should be equipped with the knowledge and skills to communicate effectively with healthcare professionals, providing accurate and reliable information about the products they promote. Emphasizing the reliance on scientific evidence helps ensure that marketing practices are grounded in the latest research and contribute to the overall credibility of the pharmaceutical industry.

Within the context of regulatory approvals, the training should delve into the specific regulations governing the promotion of pharmaceutical products. This includes understanding the limitations and requirements imposed by regulatory bodies to prevent misinformation, off-label promotion, or other practices that may compromise patient safety.

In summary, the comprehensive training for sales representatives should go beyond a cursory understanding of ethical guidelines and compliance standards. It should delve deep into ethical considerations, legal obligations, and industry-specific regulations, emphasizing the importance of promoting pharmaceutical products based on robust scientific evidence and within the boundaries of regulatory approvals. This approach ensures that sales representatives are well-equipped to navigate the complex landscape of the pharmaceutical industry while upholding the highest standards of professionalism and ethical conduct.

Transparency in Financial Relationships

Pharmaceutical companies ought to openly divulge any financial affiliations they maintain with healthcare professionals and institutions. This commitment to transparency plays a pivotal role in fostering trust among stakeholders, including patients, healthcare providers, and the public. By providing a comprehensive account of financial interactions, pharmaceutical companies contribute to the integrity of medical decision-making processes. This transparency is especially crucial in mitigating concerns about potential conflicts of interest that may arise from financial incentives, safeguarding the integrity of healthcare practices, and upholding the ethical standards of the medical profession. In essence, the transparent reporting of financial relationships is an essential element in building a healthcare ecosystem founded on trust, ethical conduct, and the prioritization of patient well-being over undue financial influences.

Enhanced Data Security Measures

In order to effectively mitigate apprehensions associated with patient privacy and data security, pharmaceutical companies should allocate resources towards the implementation of comprehensive cybersecurity measures. These measures encompass various strategies such as encryption, which involves converting sensitive data into a secure code to prevent unauthorized access. Additionally, adopting secure storage practices is imperative, ensuring that patient information is stored in a manner that safeguards it from potential breaches.

Regular audits play a crucial role in this context, serving as proactive measures to identify and rectify any potential vulnerabilities within the cybersecurity framework. These audits involve systematic examinations of the entire information security infrastructure, scrutinizing the effectiveness of implemented measures and pinpointing areas that may require reinforcement or improvement.

By investing in robust cybersecurity measures, pharmaceutical companies not only demonstrate their commitment to safeguarding patient information but also adhere to industry standards and regulatory requirements. This proactive approach not only protects sensitive data but also fosters trust among patients, healthcare professionals, and regulatory bodies. In an era where digital advancements are integral to healthcare, a strong cybersecurity foundation becomes paramount in maintaining the integrity and confidentiality of patient data.

Final Verdict

Ethics in Pharmaceutical Sales, The ethical considerations within the realm of pharmaceutical sales constitute a complex and multifaceted issue, demanding sustained vigilance and proactive initiatives from all involved parties. It is imperative to achieve a delicate equilibrium between the pursuit of business objectives and the paramount concern for patient well-being. This equilibrium is not only critical for the enduring success of the pharmaceutical industry but, more significantly, for the health and welfare of individuals who depend on these medicinal products.

Maintaining ethical standards in pharmaceutical sales necessitates a commitment to robust frameworks that govern behavior, embracing transparency in all transactions, and proactively investing in education and technological advancements. This multifaceted approach serves as a strategic guide for the pharmaceutical sector to effectively navigate the intricate challenges it faces while fulfilling its overarching responsibility to society.

The first component involves the establishment and adherence to ethical frameworks, which serve as guiding principles for the conduct of individuals and organizations within the pharmaceutical sales domain. These frameworks delineate acceptable practices, ensuring that all stakeholders operate within morally sound parameters.

Transparency stands as another crucial pillar in ethical pharmaceutical sales. This entails openly disclosing information regarding product efficacy, potential side effects, pricing structures, and any conflicts of interest. By fostering transparency, the industry can build trust among stakeholders, including healthcare professionals, regulatory bodies, and most importantly, patients.

Moreover, investing in education is pivotal for cultivating a culture of ethical awareness within the pharmaceutical sector. This involves continuous training programs for sales representatives, healthcare professionals, and other industry personnel to enhance their understanding of ethical considerations, regulatory compliance, and the societal impact of their work.

Technology plays a transformative role in bolstering ethical practices within pharmaceutical sales. Implementing advanced systems for tracking and monitoring transactions, ensuring data security, and leveraging artificial intelligence for compliance checks are examples of how technology can be harnessed to mitigate ethical risks.

By embracing these multifaceted measures, the pharmaceutical sector not only safeguards its own sustainability but also fulfills its ethical obligation to society. This commitment to ethics not only enhances the industry’s reputation but also contributes to the overarching goal of providing safe and effective medications for the betterment of global health.

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FDA Form 483 and Warning Letter, How do differ from each other?

FDA Form 483 and Warning Letters:

It is very important to know how the Warning Letter and FDA Form 483 are issued by the Food and Drug Administration (FDA) after an inspection of a particular drug manufacturing site.

FDA Form 483 and Warning Letters are often confusing for many pharmaceutical professionals, who cannot properly differentiate between the two. Both communications are issued by the Food and Drug Administration (FDA), usually after a regulatory inspection and never before a regulatory inspection.

FDA Form 483

FDA Form 483:

Form 483 lists observations in order of importance that FDA inspectors record during manufacturing site inspections. Each observation noted on the FDA Form 483 is clear, specific and significant and FDA investigators are specially trained in the matter.

FDA officials communicate their inspection observations on Form 483, and it is usually issued to the manufacturing site after the FDA audit is completed. Observations are not generally made until the investigator’s judgment, conditions or practices observed that any food/drug/device/cosmetic has been adulterated/changed intentionally to its standard practice.

After completion of the Inspection, FDA Form 483s, are discussed with a company’s senior management, regarding the observations of the inspections. To get a full understanding each observation is read and discussed with the company’s senior management so that they get the actual situation regarding inspection observations.

An FDA Form 483, is a report, it does not contain any observations of questionable, or unfamiliar significance at the time of the inspection of a specific firm. It only reports on familiar objectionable conditions. which are observed during the inspection. even if it can’t report other objectionable conditions which didn’t notice during the inspection. The company/Firm is only responsible. to correct the objectionable conditions which are noticed after the completion of the inspection on the due date.

How to handle FDA Form 483?

Upon completion of the FDA inspector’s manufacturing site inspection, the manufacturing site authority should discuss all findings with the FDA inspector and make every effort to resolve negative observations before the inspector leaves the site.

If errors and miscommunications occur, it is best to consult with inspectors.

Try to understand the positive or negative mood of the regulatory body; Their mood can be negative for various reasons or for no reason at all.
Without any hesitation ask any questions to the inspector regarding confusion found during observations.

If you think, you can convince the inspector. Try to convince the inspector/inspectors regarding observations found during inspection with the help of related information. Your convincing power may help to delete some observations from FDA 483.

The purpose of an FDA Form is to notify the company’s senior management regarding objectionable conditions. The FDA Form 483 is presented and discussed with the company’s senior management after the completion of the inspection. Senior management of the Companies is encouraged to respond to the FDA Form 483 with a corrective action plan within the due date.

See Practical Example of

Form 483:

Form 483 for Stryker Craniomaxillofacial Division. Portago, MI.

Form 483 for Teva Parenteral Medicines, Inc. Irvine, CA. Form 483.

Form 483 for Cipla Limited Compliance Record.

Form 483 for Ranbaxy Laboratories Limited.

Form 483 for Lupin Limited.

Warning Letter

Warning Letter for Cipla Limited.

Warning Letter for BioMD Plus LLC.

Warning letter for Walmart inc.

Warning letter for Elements brands inc.

Warning Letter for Alber GmbH.

It is mandatory to respond to the FDA Form 483 within 15 days otherwise regulatory agency will not consider your response regarding the final observation of your company.

FDA Form 483 is not the final decision maker. It just considers along with a written report known as Establishment Inspection Report. All evidence or documentation collected from the manufacturing site, response made by the company/firm. The agency considers all of the information and then they made the final decision for further action.

You may avoid the issuance of a Warning Letter if you respond to FDA Form 483 within due time with appropriate justification.

Form FDA 483 content

Header information

It contains the following information:
[] FDA district office Address and phone number
[] Date(s) of inspection
[] Facility’s FEI [FDA Establishment Identification number].
[] Name and title of the individual to whom the 483 is issued
[] Address of the facility that was inspected and
[] Brief description of the type of facility

Observations

This section presents all the listed observations made by FDA investigators [Number of Investigators may be one to three persons or as per FDA policy]. This section contains all of the inspectional observations and this is not the final agency decision. You can consult with the FDA investigator regarding the observations and also can share your plan and implementation regarding observations. If you have any questions you can contact with FDA with the header section and contact number.

Annotation

During the final discussion, the actual annotation of the 483 occurs with the firm’s management. If the firm management prefers no annotation, then it will not happen. Annotations may be placed at the end of each page or at the last page of the observations where the investigators generally put their signatures. In 1997 FDA introduces an annotation policy for medical device inspections.

Signatures

For multiple pages, the FDA investigator’s signatures have on the first page and the last page only other pages only initialed. All investigators’ names are printed and signed, & issue date is recorded in this section. FDA investigator’s title may be included there.

Reverse side

This side contains some instructional text regarding Food, Safety, and device cosmetics. And also contains some instructions regarding FDA investigators to their nature of work in the inspected site. All the instructions mention these sections are backed by their specific reference such as

-Pursuant to Section 704(b) of the Federal Food, Drug, and Cosmetic Act
-Section 704(b) of the Federal Food, Drug, and Cosmetic Act

FDA Warning Letter

Warning Letter:

The next step after issuing FDA Form 483 is Warning Letter. FDA may issue a Warning Letter to the manufacturing site which has already been visited and inspected by FDA Inspector. Serious violations of the quality of the product may lead to the issuance of a Warning Letter. Generally, Warning Letter is issued by the higher officials of the FDA after the review of the inspection observations and especially reviewing the product quality matters.

After the issuance of FDA Form 483 and completion of the inspection, a regulatory agency may issue a Warning Letter to the manufacturing site. When any serious issue is found regarding the quality of the product, a Warning Letter is issued by the higher officials of the FDA after the review of the inspection observations. It contains evidence and detailed explanations for the observations. FDA high officials generally concentrate on the quality of the product and do not compromise with it.

A Warning Letter should be replied to within the given time because a delay can lead to an import ban. It may be asked for an extension of the time to justify the things. Most of the Warning Letter issued by FDA high officials has the quality or cGMP issues of the product or facility.

You may easily find both FDA Form 483 and Warning Letters on their website due to these are published immediately publically on fda.gov. and anyone can get it.

Type of warning letter

General FDA Warning Letters
Tobacco Retail Warning Letters
Drug Marketing and Advertising Warning Letters

General FDA Warning Letters

This type of warning letter is issued when FDA found that the manufacturer has significantly violated FDA regulations. Poor manufacturing practices, problems with claims for what a product can do, or incorrect directions for use lead to the issuance of General FDA Warning Letters. The problem mentioned in the warning letter must correct by the company and the action plan to be shared with FDA and subsequent interaction may change the status of the issues mentioned in the letter.

Tobacco Retail Warning Letters

tobacco retailers occur periodically face Compliance check inspections under the Family Smoking Prevention and Tobacco Control Act (Tobacco Control Act) and the Regulations Restricting the Sale and Distribution of Smokeless Tobacco and Cigarettes to Protect Children and Adolescents. Cigarettes and smokeless tobacco also include in compliance check inspections.

Drug Marketing and Advertising Warning Letters

Letters are collected and sorted by month and only cover drug marketing activities. Some of the letters may be edited to remove confidential information. Letters sent electronically may be engaged in illegal activities.

Close-Out of Warning Letter

Warning Letter “close-out letter” issued by FDA. Once the agency completed the evaluation of corrective actions taken by the manufacturing site in response to the Warning Letter and the agency found the corrective action satisfactory then the agency may issue a close-out letter. A ‘close-out letter’ will not be issued depending on some action taken by the firm. The corrective action must be verified by FDA. The agency expects that corrections have been implemented and verified by follow-up inspection.

If any violations exist that can’t be corrected then no “close-out letter” will issue. Future FDA inspection may further assess the violations and enforcement action may be taken without prior notice.

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user requirement specification of Equipment

User Requirement Specification is a specific document where end user generally defines needs, target, goal and their expectation for a system, service and product. This is actually blueprint for the development personnel and it help to ensure that the product meet the target for the specific group.

A standard User Requirement Specification includes information about the user group, targeted use of the product, functional requirements, Operational requirements, and performance requirements. It also contains constraints or limitations.

A standard User Requirement establishes a better understanding between the stakeholders regarding a defined outcome; also sets a specific goal for the end-user and helps to save the project, and product delivery time the best thing is its budget-friendly; the user can previously estimate the cost of the specific project.

URS is generally developed by the buyer defining all listed requirements. After the development of a URS, the user sent it to the equipment manufacturer to prepare it as per predefined criteria.

A poorly developed URS is always creating confusion for the manufacturer, you can see the poorly written URS at the manufacturer’s end and If you don’t know how to write URS then you can ask standard URS template from the manufacturer, they are happy to help you. If supplied Template is found near your requirements then you can go with a modified version.

User Requirement Specification when disregarded?

A confusing URS is always disregarded. If the manufacturer can’t read you then the faulty or wrong machine can be developed which can destroy your project and A meaningful and well-written user requirement specification saves time and money; also reduce misunderstanding among the manufacturer.

A series of emails may generate to explain your requirement to the manufacturer which may express your poor level of understanding of the specific requirement also create of the high chance of wrong specification delivery and You have to express the requirement what exactly you are looking for in your User Requirement Specification (URS).

Keep it simple, Specific, and Better user requirement specification creates better outcomes.

Requirements of user and support design, qualification activities, operations, commissioning, and maintenance are mainly present on the URS. It’s good to set your mind at the start of your dream project.

According to Mark R. Smith, MD, Realtech,

“A standard URS shall be clear, jargon-free, easily readable, not hard to understand which helps to software engineer and Designer clearly readable and understandable of the user requirement with minimum cost and maximum output”.

Types of Requirements

There are several types of requirements that are depicted here.
[] Business Requirements
[] Functional Requirements
[] Stakeholder Requirements
[] Non-Functional Requirements
[] Transition Requirements

What thing to consider for user requirement specification (URS)?
Two main things shall be considered during the writing of URS, number one: What shall be included and number two what shall not be included.

What to include:

During the writing of the URS, the actual information shall be included in the URS. More information may require for big projects and less for a small project the basic of all URS shall be specific. Unknowingly including a feature that is not available in the market is the same as knowingly ruining your project.

Knowing then any feature should be included in the URS. The most important thing is to include only those specifications that are necessary. Features that will never be used need not be included but the facility to use updated features can be retained.

What not to include:

Ambiguous words or terms, Features that are not easy to understand, and that no one has yet used, features that are not user-friendly and will never be used, and features that are overpriced but less important shall be avoided.

How to proceed with your User Requirement Specification?

Before proceeding with your URS, define the responsibility of the stakeholders in your URS then collect all stakeholders’ signatures with designation and date. An approved URS shall be procced to the manufacturer to avoid any wanted circumstances. To sign a document means that you are responsible for it.

What should be included in the Introduction section?

In this section, you should describe more briefly about yourself and why this URS has been raised. Give a short description of your organization. Like “We are Startech is a startup organization in west Virginia. We want to install a high tech tablet compression machine to produce almost 6000K tablets per hour. This user requirement specification (URS) documents the user requirements for producing tablet dosage forms in a tablet compression machine.

The objective of the User Requirement Specification

They clearly describe the goal of the project so that anyone understands it. A brief overview of the project shall be included. Mention the actual purpose of the URS.

Who will write the User Requirement Specification?

Anyone can write URS, who has a thorough knowledge of the system, service, product, or machine in question. But you don’t let someone write something they don’t know about, for example, production personnel can’t write the URS of quality control equipment and vice versa.

How to document a User Requirement Specification?

The user will prepare the URS and another SEM will check the URS and Engineering personnel and the head of the user department will Review the document, finally Head of Quality will approve the URS. Always documented hierarchy shall be maintained.

To write user requirement specifications for a pharmaceutical company equipment following points should be included

1. Front Page: URS no., Revision no., Addendum no., Using Facility shall be mentioned.
2. List of revisions: Revision number shall be mentioned (if required).
3. List of addendums: Addendum to be mentioned (if required).
4. Table of Contents: Write the list content of the URS.
5. List of abbreviations: All abbreviations shall be mentioned.
6. Signature page: Signatory page contains all signatures including Approval authority.
7. Scope: The scope of the URS is to define the specific Equipment/Instrument.

8.0 Procedural Document Requirements:

This part gives information about the Equipment / Instrument including the Purpose of the Equipment, Specification, Qualification, etc.
8.1 Name of the Equipment: Name of the equipment to be mentioned here, if possible, and Model No. to be defined here.
8.2 Purpose of the Equipment: Purpose of the Equipment shall be clearly defined here.
8.3 Number of Equipment Required: Require quantity of the Equipment/Instrument shall be defined here.
8.4 Qualification: A list of qualification documents shall be mentioned here.
8.5 Specification of Equipment: All major specifications of the Equipment/Instrument shall be mentioned here.

9.0 Operational Requirements:

9.1 Vendor Scope: The Vendors scope shall include the Supply, Installation, and Documentation including calibration certificates, User training, and Details of service/maintenance contracts available.
9.2 Operation: Basic operative characteristics including Data logging (21 CFR part 11), controlling system, capacity, safety, and protection, the capacity of basic function, etc.
9.3 Options and Ancillaries: The vendor should identify, where applicable, their standard equipment that fits this specification. The vendor shall (where possible) also provide costs including, A range of additional maintenance support and services., Any additional accessories to fulfill the requirements indicated in section 9.2.
9.4 Interfaces: A user-friendly control system is required, that can allow system operation with a minimal amount of training.
9.5 Data and Security: If required, data and security articles are to be clearly defined here.
9.6 Environment: Instruments/Equipment’s operating environment should be clearly defined here. The operating area must fit with the specific Instruments/Equipment in such a way that it can be operated without any difficulty.

10.0 Constraints

10.1 Milestones and Timelines: A projected timeline and milestone may be set here.
10.2 Compatibility and Support: The internal components of the system must be compatible with, and resistant to, the materials used during operation. Operating power to be mentioned here.
10.3 Maintenance Requirements: The manufacturer should supply details of any maintenance/breakdown packages available.
10.4 Procedural Constraints

11.0 Life Cycle

11.1 Development Procedures: Future development procedures are to be mentioned here.
11.2 Testing Requirements: See Section 11 for a detailed matrix of the validation testing requirements.
11.3 Delivery Requirements: On supply, the following documentation should be supplied: Operation and maintenance manual (including manufacturer’s recommendations for maintenance schedules). Calibration certificates. Parts list and spare requirements. System specifications.
11.4 Support: The vendor must supply details of all service and maintenance requirements of the equipment. The vendor must also supply details of any service and maintenance support that they can supply.

12.0 GMP Requirement: A list of cGMP requirements shall be mentioned here.
13.0 Utilities Available at The Site of Installation: Utilities shall be described here including the power supply for the machine/equipment.
14.0 Documentation Requirement: A list of documents shall be described here such as Operation, cleaning, and maintenance manuals for equipment as well as the operation, Installation instructions/ guideline, other drawings (such as Mechanical, electrical, instrumentation, etc.), IQ/OQ documents & operating manual., Instrument calibration / Qualification certificates traceable to the national reference standards, Guaranty/ warranty certificates for the equipment, Shipping checklist, and Hardware design specification.
15.0 Terms and Conditions to Be Included in The Quotation: All the terms and conditions shall be described here.
16.0 All the discussion shall be noted here and contact personnel details shall be mentioned at the end of the discussion details.
17.0 Annexures: Mention annexures if there are any.
18.0 Validation Requirements:
The following details the test requirements for documentation, testing, and the stage of the project at which they must be provided/performed. These requirements are a minimum tariff, and the vendor is required to include any documentation, not already requested here, which is considered necessary to support the successful validation of the system.

Which things to follow to write a Modern User Requirement Specification?

From the discussion till now we know what to add to our URS and what not to add. Ambiguity to be avoided as much as possible should be written clearly so that anyone who reads it can understand it. Ambiguity is the enemy of any project’s success and expressing yourself as accurately as possible is possible. Communication must be done in an unambiguous manner to achieve good results; Your project will be successful when you are able to convey your message to others.

To write a best User Requirement Specification you need to keep the following points in mind:

user requirement specification
user requirement specification

1. Focus on Single Requirement:

Check each requirement to be developed and how it is tested. Project success depends on each effective requirement which is really a demand to the project. Avoid unnecessary requirements which really not essential to the project.

2. Avoid Haziness

Your URS must be clearly written. Use a Simple Sentence. No confusing word. Just say what you want and what not.

A user requirement specification should be clearly written, using simple sentences, and without ambiguity. Examples of ambiguous words are:

[] Easy
[] Strong
[] Improve
[] Fast
[] Slow
[] Enough
[] User friendly

What exactly are you meaning “Fast”? this term is theoretical; you can’t actually express your requirement using the word “Fast”. It is hard to measure. Avoid any abbreviations, acronyms, and jargon words (words and phrases, that are not generally understood).

3. Go with the SMART Approach

[] S for Specific
[] M for Measurable
[] A for Achievable
[] R for Realistic
[] T for Time-bound

SMART [Specific, Measurable, Achievable, Realistic, Time-bound) targets offer a decent way to confirm your URS is well-defined and supportable.
Specific: All requirements mentioned in the URS must be specific, clear, and jargon-word-free. Don’t add any unnecessary requirements like easy and fast. Mention the actual specification.

Measurable: Reequipment must be measurable, don’t state anything which can’t confirm by testing or examination. Always avoid theoretical statements like rapid and swift. It can’t measure, you can’t prove that your requirements just met the specification until it is measurable.

Achievable: Never set a requirement which is can’t achieve with help of current technology. A feasibility study shall be done before setting any requirements. You can’t set any requirement which is technically impossible to achieve. It is wise to study well before adding features that you have no idea about. If even then you cannot be confirmed, then seek an expert for help. It is not right to add any feature without knowing it.

Realistic: It’s important to be realistic when determining the list of requirements. Sometimes technically achievable requirements may not be realistic due to regulatory requirements, time restrictions, Budget constraints, or other limitations.

Time-bound: A specific time frame shall be fixed to obtain your project. Even after finishing everything and if the specified time is not fixed, then any project may fail.

4. Organize

Organize your word choice and think carefully about it. Generally, the word “Shall” and “will” define the actual requirement which must be met. Word like “May” and “Could” use to define goals than are expected but not necessarily requirements. So, when you want the requirement must be met then use shall/will and use may/could for not mandatory cases.

5. Control Changes to the Requirements

Any type of changes may require during creating your list of requirements. Changes to the specification of the specific requirement shall be controlled. If any type of change directly affects the requirement, then the requirement shall be updated and a new version shall be created.

6. Requirements Must be Testable

Requirements shall be written in a such way that they can be tested and Specific requirements shall be traceable through the life cycle of the system/service/equipment/instruments.

7. Structural Products

Two types of products may be used as structural products & custom applications; for custom applications, the manufacturer must describe every process step to the user. For structural products, the process steps must be aligned with their predefined specification.

8. Vendor Audit

Most of the cases Regulated companies are most aware of their vendor for periodic assessment. All types of assessment/re-assessment perform in accordance with the Quality Management System (QMS).

9. Specifications

It is essential for the supplier to thoroughly document both the functionality and design of the system which is a prerequisite to ensure successful product development. Documentation must cover all aspects of the system, including software, hardware, and configuration, to meet all requirements to be established.

10. Training & Documentation

The supplier must agree to provide comprehensive system management documentation and provide instructions for both maintenance and use by the supplier and related issues must be agreed upon prior to system purchase.

11. Eliminate Requirement Redundancy

Avoid overcomplicating the system requirements and there is no need to bulk it up by duplicating it. Avoid duplication. Duplicating your documents may require more testing, documentation, and review time, making the project and time progressively longer Don’t include anything which is related to money or finance.

What is the difference between data and information

12. Embrace the Opportunity to Evaluate Vendors

Conducting audits on suppliers may include asking the following questions:
[] Security
[] Product support
[] End User training
[] Company Overview
[] Use of sub-contractors
[] Service delivery process
[] QMS application at the company
[] Development product life cycle
[] Key products development plans
[] Organization, roles, responsibilities, & training

13. Don’t be intimidated by your vendor comparisons

Utilize your URS to evaluate different vendors & note their advantages and disadvantages. If new information is found during the initial stage, feel free to revise your approved URS accordingly through the change control process. It is acceptable to make modifications or adjustments to the requirements to fit your needs until the final approval of the URS and it shall be revised the approved User Requirement Specification accordingly maintaining proper documentation.

14. What ought to be included in the URS?

The contents of a URS naturally include the following (but are not limited):
[] Functional requirements
[] Operational requirements
[] Technical requirements
[] Interface requirements
[] Data requirements
[] Security requirements
[] Regulatory requirements
[] Maintenance requirements
[] Availability requirements
[] Migration of any electronic data
[] Environmental requirements
[] Constraints to be observed
[] Life cycle requirements

15. Categorize Your Requirements

Categorize Your Requirements as-
[] Mandatory (High)
[] Beneficial (Medium)
[] Good to have it (Low)

16. Subjective Knowledge and Processing Step

To ensure that requirements, your professional knowledge is essential but not mandatory; if require you can seek help from an SME [Subject Matter Expert]. To identify key requirements of the system Process knowledge is required which are related to the manufacturing/servicing process. Look for the following key points-
[] Experience
[] Knowledge
[] Documentation

17. The requirements may be incomplete or not fully specified

Sometimes the requirements are not fully understood at the beginning of the project; Requirements evolve over time. URS shall be developed as per requirements when information is available. Don’t share incomplete User Requirement Specifications to the manufacturer to avoid any unwanted requirements.

Frequently Asked Questions

Are URS always required for validation?

At the initial stage of system/service/equipment/instruments, then URS is a valuable tool for ensuring the asking requirements. When an existing system is being validated then URS consider as a functional requirement. These two documents can’t be considered as single documents.

What is the benefit of good User Requirement Specification?

Requirements gathering is an important part of a good software/hardware/service/product development project. Good estimation, improved customer satisfaction, reduced cost, and project duration can all fail if good requirements are not selected and sufficient knowledge is not introduced in the selection If you are unclear about what you are delivering, no one can expect anything better from you.

There are Five main questions that shall be asked to develop any project:
[] Why we are doing it?
[] What do we need to do it?
[] What is the benefit?
[] How do we do it?
[] What is the timeframe?

If we fail to estimate project requirements or are unable to assume what is the requirement, can lead to a poor outcome of the project, and also lead to extra manpower, longer duration, and project costing.

Download Your

User Requirement Specification (URS) Template

user requirement specification of Equipment Read More »

What is the difference between Mass and Weight?

What is the difference between Mass and Weight? Generally, people, treat them same term in practical life but in physics, they are very much different. One is in practical matter another is variable place to place, Hight to Hight depends gravity. What is gravity? force that exists among all material objects in universe. Express as g & it change place to place, Hight to Hight but one thing that is not change, this is it. It is Mass.

If you in Australia your mass is 59kg, if you in UK you are in 59kg if you in USA you are in almost 59kg, if you in Mars, obviously you are in 59kg. It can’t be change. This is just like your personality which never change other is your attitude which always chance place to place.

So, what is the definition of Mass?

Thousands of types of definition you will find in web but I like the following-

Mass can be defined as amount of matter present in you. No matter at what place you are may be in Africa or Europe its value remains constant.

What is the definition of Weight?

Weight is the force by which you are being attracted by this amazing planet. This is very much changeable from planet to planet & height to height. Gravity on Mars is 38 percent of Earth’s gravity, so a 100kg person on Earth would weight 38kg on Mars.

On the other hand, we can say that Mass is actually a physical quantity which measures amount of matter in a body whereas weight is actually the force with which earth pulls our body towards its own center.

How can we express them?

Generally, Mass is express by “m” and its S.I. unit is kg where as Weight is Expressed by “W” and its SI unit is N[Newton].

Weight is mainly the amount of forces force exerted by earth on a mass of any substance. Weight can be calculated as Weight=Mass x g, where g is acceleration due to gravity and its value is 9.8.

Let me explain,

If want to something buys from supermarket or any place where you prefer, may be online, they will mention mass of the Object not weight in practical though some of the company mention weight of the object but actually that it the mass of the object not weight of the object.

You will only get the weight of the object, when you multiply the value with “g”. So, if your weighing machine gives the reading for a object as 100kg then it weight will be 100×9.8=980N. Hope you got it.

Value of the weight is negligibly change in the earth surface as the value of the “g” is not significantly change on our planet surface but a little amount change in poles of the earth as the value of “g” slightly increase inversely in equator area the value decrease.

Evaluation of Mass & Weight

From the very beginning, people are involving their goods for trading. 2-pan balance scale and some reference weights were the primary transaction method to determine the quantity of item. Balance was achieved by placing unknown amount of goods to one pan and another pan contains reference weight. The main problem of the two pan scale was it can’t measure the force only measure the mass.

At the time of the advent of English, the traders referred their known item to compare to the another unknown item as “weights”, and this process known as weighing and thus the result ,mentions as weights at a little before 1000AD.

In late 1600, famous laws of motion developed by Isaac Newton’s but this is not quite accurate in extremely high speeds where theory of special relativity [Albert Einstein’s at 20th-century] is required. Mass depends on how much matter-atoms is an object.

Lot of research on relationship between the quantity of matter & effect of force on that matter, especially with the concept of gravity was performed by Newton & Hooke at 1600s. After the completion of the research, they publish their research paper in Latin as that time it was major communication medium in scientific research.

At 1700s, the Newton and Hooke works start to publish in English and in this process the decided the take the word “Weight” as amount of material which is already use for the centuries and its related to gravity and taking the word “Mass” [ which was unrelated meaning in that time] and having it mean to the amount of material [Similar meaning of Weight as that was using in that time]. So, the great confusion starts then. This was the fault of physicists & their translators.

Mass can be defined as the measurement of an object’s tendency to resist changing its own state of motion, well known as inertia. Left a football on a field will stay put or move in a straight line unless some force like friction, touch by foot or hand or creating obstacle to the line, it will keep moving forward. So much is the measure of force which will require to change its path.

Weight, can be defined as the measure of amount of downwards force that gravity exerts on a specific object. If the mass of the object increases then force increases, the more inertia it contains, then harder gravity pulls. On our Earth’s surface, force of gravity is almost 9.8 newtons per kg.

As the two term was confusing so people involve in trade, law, commerce had no interest to change the long use term “Weight” and continue it. Weight to them, physicists started calling mass already and this practice continue still today.

People who are involving in commerce & Law use the word “Weight” to define the amount of material where never involve the meaning of force and never implement the word “Mass”. At the year of 1750, spring scale was invented and it calibrated to read out the mass which surprisingly works very fine until it moved to significantly different strength of gravity. In our planet, the change of gravity is almost same until it Moves to poles or equator, if do so then change of gravity is not significant. So the traders continue to use the word “Weight” as they are using this term for a long period of time to define the word “Mass”.

At the period of time, physicists start proclaiming that the effectiveness of the Word “Weight” and “Mass” is correct and anyone who used them otherwise is very much incorrect and such shall be obsolete. This is totally insane as the physicists were violating the long-term usage of word “Weight”. They also emphasize the usage of word “Weight” referring forces. But this didn’t reflect the practical life. In practical life, in Commerce and Law, it is very much considered that the Weight is the synonyms of Massa and its correct is kilograms not newtons.

In this context, this is very much meaningful that “I weigh 99 kg” or “My weight is 99 kg” but as per Physics weight is the result of Mass and associated with gravity on its which unit is Newton not kilogram. As discussed, it can’t say forcefully that they are using the terminology incorrectly, moreover in some context the answer of the question is “There is no difference between “Weight and Mass” due to they are synonyms to each other and measured in kilogram.

But there is a clear distinction between the two terminologies where Mass is the amount of material which measured in kilogram and Weight is type of force with Mass measured in Newton. In technical field all of the measurements are associated with the Organization titled as “Weights and Measures”.

As per Scientists “Weight is measured in Newton[N] which is 9.8 times larger than Mass[m] in earth surface and this may vary from place to place [Earth to Moon, Earth to Mars, Earth to Saturn etc.] 10kg of Mass has Weight of 98N and this has the Weight in Moon has 10.6N in Moon.

To simply understand the difference between Weight & Mass is” Mass is the Personality of Matter and Weight is its own attitude which is variable to place to place”.

Mass is actually the intrinsic property of matter which is just like the like personality is of a man and weight is the gravitational pull on the specific object which depends on the other body which is employing on it which is similar to attitude depends on another party.

Expression of Weight and Mass
As per Physical Science, the Mass and Weight are the totally different and their expression is “m” for Mass and unit is kg where Weight express as m x g [g, acceleration due to gravity] and its unit is Newton.

Let consider Mass is m, then
Weight= m[Mass] x g[acceleration due to gravity]

What Is the Difference Between Weight and Mass?

In ordinary conversation, “mass” and “weight” are used interchangeably but they are very much different to each other. Mass is defined as the amount of material present in the matter where Weight is measured as how force of gravity acts on that mass. Amount of matter in a body is measured by mass and Express by “m” or “M”. The amount of force acting on a mass due to the acceleration due to gravity is measured by Weight and it’s the result of Mass multiplied by acceleration of gravity (g).

The values for mass and weight are the same if it does not move on Earth. If you change your location from low to or high to low gravity then the Weight of the Object shall be change but its mass remain same in any location as mass is not location dependent. You can think that your mass of the body is always same but your Weight shall be different on Mars compare to Earth.

Difference Between Mass and Weight

Sl. No.Differentiating PropertyMassWeight
1DefinitionMass is the measure of the amount of matter in a body.It is the measure of amount of force acting on a mass due to acceleration due to gravity.
2CriteriaMass of an object is same in everywhere as Mass is a property of matter.Weight always increases or decreases with higher or lower gravity as Weight depends on effect of the gravity.
3ValueMass is a constant Value and Mass can’t be zero in any place.If no gravity acts upon an object, as in space then Weight can be zero as 0 [Zero] gravity acts on the mass.
4LocationAs per location, Mass does not changeDepends on location, Weight varies accordingly.
5DenotationMass is denoted by “M”.Weight is denoted by “W”.
6MeasurementAn ordinary balance can be used to measure Mass.A spring balance is used to measure Weight.
7UnitMass generally is measured in grams and kilograms.Weight measured in newtons which is a unit of force.
8FormulaMass is always constant value for a body and there are several formulas to calculate the mass.
Mass can be calculated as:
Mass = Volume × Density
Weight is the measure of the gravitational force acting on a body.
Weight can be calculated as:
Weight = mass × acceleration due to gravity[g]
9Gravitational EffectMass does not depend upon gravity and is constant everywhere in the universe.Weight is dependent on gravity and so, it varies from place to place in the planet.
10Measuring InstrumentMass can be easily measured using any ordinary balance like beam balance, lever balance, pan balance, etc.Weight can be measured by a spring balance or by using its formula.

If I go other Planets then How Much I Weigh on there?

Due to acceleration to gravity the weight varies dramatically but person’s mass doesn’t change elsewhere in the solar system. The “surface” distance from the center of gravity plays a major role to calculate the gravity on the mass. When you travel on the top of the mountain [The Himalayas] your weight shall be slightly lower than the sea level. Always mass is not the major as mentioned before, distance plays a significant role.

Suppose, If I in Saturn, my weight will not increase Saturn 95.2 times as Saturn is 95.2 times heavier than earth due to its surface is so much far [1.4075 billion km from Earth] from the center of the earth. To get the actual weight of a person just multiply the appropriate number of Earth Gravity. For Example, 100-pound person shall be weight on 113.9-pound on Saturn or 1.139 times weight on Earth.

Different Surface Gravity on different Planet

ParticularsMultiple of
Earth Gravity
Surface Gravity
(m/s2)
Earth1 (defined)9.8226
Jupiter2.64025.93
Mars0.38953.728
Mercury0.37703.703
Moon0.1651.625
Neptune1.14811.28
Sun27.90274.1
Saturn1.13911.19
Uranus0.9179.01
Venus0.90328.872

Above the explanation, your weight will be same in Venus as the planet has the same size and mass as Earth. You feel slightly higher weight in Neptune and Saturn but less feel in gas giant Uranus. Almost same weight shall be assumed in Mercury and Mars though Mercury is much smaller than Mars[30% wider than Mercury].

If sun become cold [not possible in near future as assumed] you will feel 28 times much weight compare to Earth surface as it’s the more massive in our solar system.

What is the difference between Mass and Weight? Read More »

Data Integrity and Why Is It So Important?

Data Integrity can be defined as it is critical part to the plan, execution & practice of system that processes, stores & or retrieves data and maintenance & assurance of data accuracy and consistency throughout its life cycle.

Another best alternative term is Data quality which is sometimes defined as the proxy term of data integrity. It is the wide term & it can be used in different meaning depending on the framework. For data integrity, data validation is prerequisite. Data corruption is the just opposite term of Data integrity.

Also Read

What is the difference between Data and Information?

Confirm that data is recorded exactly as projected and most of the cases Data Integrity technique is the same for all type of probable data source.
The main target regarding is to prevent any type of alteration of the exact data recorded during collection of data and it can’t change at any cost. At the time of retrieval of data, it must be same as collected before.

Data Integrity denote the accuracy & consistency of data over its lifecycle. Sensitive data may loss upon uses of Negotiated data. Under this consideration, continuing it is a main focus of many enterprise security solutions. During replicated or transferred of data, it shall be intact and unaltered. To ensure the integrity of data, Error checking methods and validation procedures are typically best way to serve the same.

Don’t confuse with Data Integrity and Data security, it is process to prevent unauthorized entry to the projected data or protecting data from unauthorized expert.
Any unintended changes to data as the consequence of a storage, retrieval or processing operation, including malicious intent, unexpected hardware failure, and human error, is failure of data integrity.

Failure of Data Integrity means any unplanned changes to data as the consequence of storage, unexpected hardware failure, retrieval or human error or processing operation malicious intent etc. If you unable to protect your data from unauthorized change then it can define as data security failure.

Data Integrity denote that it is a state as well as process, so a confusion may arise. Data Integrity is a state as it denotes a data set is both valid and accurate. Validation methods & Error checking are considered as Data Integrity processes.

Study of Data Integrity

Data Integrity is significant for several reasons & need to maintain the same. Data Integrity confirms searchability, recoverability, connectivity, & traceability. To increases stability & performance as well as improving reusability & maintainability; need to protect validity & accuracy of data. Data plays a major role to drive enterprise decision-making and data undergo several stages of changes to form raw to format to become more practical and identifying relation between them. In modern enterprises Data Integrity consider the top most priority.

In a database system, Data Integrity may be Compromised in various type of ways. In the following ways, Data Integrity may be compromised-
[][]Compromised hardware, like device or disk crash
[][]Compromise of Physical devices
[][]Cyber threats, Bugs, Viruses/Malware, Hacking, & other unfamiliar process
[][]Human error, whether unintentional or malicious

Transfer errors, unintended alterations or data compromise during transfer from one device to another device.
Most of the cases, some type of data security may protect this data compromises. Data duplication is the critical para meter for data security as well as data backup process.

Data Integrity & Databases

Data Integrity encompasses strategies for data specifying, retention, or guaranteeing the length of time data. Any lessening of enforcement could cause errors in the data; all of the rules shall be consistently & regularly implemented to all data entering the system.

At time of data input, checking system shall be implement which will lessen up the number of data error for the system. Data Integrity rules shall be strictly implemented to the system which will save troubleshooting time, erroneous data subsequently errors to algorithms.

A standard Data Integrity rules must have the strict definition regarding data relation; as which type data shall link with which type of data. A selling record of a item of certain product may be linked with the specific product but is shall not be related to unrelated data such as company asset, policy, loan, promotion etc. Based on predefined rules, it may be included check & correction system for the invalid a data.

Data derivation rules shall be applicable, mentioning data derivation procedure that how a data value shall be derived based on contributors, conditions and algorithm of the system. Re-derived procedure for data value shall be mention on which condition shall be considered for this process.

Types of Data Integrity

Organizations can maintain Data Integrity through integrity constraints, which define the rules and procedures around actions like deletion, insertion, and update of information. The definition of Data Integrity can be enforced in both hierarchical and relational databases, such as enterprise resource planning (ERP), customer relationship management (CRM), and supply chain management (CRM) systems.

Organizations can achieve it through the following:

Physical Integrity

Physical integrity deals with challenges which are associated with correctly storing and fetching the data itself.

Physical integrity indicates the right storing & fetching the data itself & its associated series of challenges. Various types of Challenges are involved with it such as Physical flaws, design flaws, power outages, electromechanical faults, corrosion, material fatigue, natural disasters, environmental hazards such as ionizing radiation, high temperatures, pressures & g-forces [the force of gravity].

Various methods are available to maintain the physical integrity such as UPS [uninterruptible power supply], redundant hardware, various type of RAID arrays, error-correcting memory, radiation hardened chips, clustered file system, watchdog timer & cryptographic hash function for critical system.

Error-correcting codes is extensively use as error detecting algorithms in Physical integrity of data management systems. Simpler checks & algorithms as the Damm algorithm or Luhn algorithm is use to detect Data Integrity errors. This system is use to uphold Data Integrity at manual transcription from one computer system to another computer system through a human intermediary such as credit card numbers. Hash functions are more beneficial to detect Computer-induced transcription errors.

These techniques are used together to ensure various degrees of Data Integrity in production systems such as a fault-tolerant RAID array may be use to configured a computer system but in silent data corruption block-level checksums might not provide.

In a nutshell, Physical integrity means protecting the accuracy, correctness, and wholeness of data when it is stored and retrieved. This is typically compromised by issues like power outages, storage erosion, hackers targeting database functions, and natural disasters, which prevent accurate data storage and retrieval.

Logical Integrity

It is concerned with correctness or rationality of a piece of data provide a particular context. It denotes the topic such as Entity integrity & referential integrity in a relational database system. Design flaws, software bugs, and human errors are the major challenges. Foreign key constraints, check constraints, program assertions, and other run-time sanity checks are the common methods to ensure logical integrity.

Design flaws & Human errors, both are the common problems for physical and logical integrity which must be properly deal with the contemporaneous requests to record and retrieve data. Physical error for a specific data system is more critical than logical error. If a data system suspected to logical error, it can be reused by overwriting with the new one but if it faces physical error then the data sector is totally used of its own condition.

Logical integrity ensures that data remains unchanged while being used in different ways through relational databases. This approach also aims to protect data from hacking or human error issues but does so differently than physical integrity.

Logical integrity comes in four different formats:

Entity Integrity

Entity integrity is a feature of relation systems that store data within tables, which can be used and linked in various ways. It relies on primary keys and unique values being created to identify a piece of data. This ensures data cannot be listed multiple times, and fields in a table cannot be null.

Referential Integrity

Referential integrity is a series of processes that ensure data remains stored and used in a uniform manner. Database structures are embedded with rules that define how foreign keys are used, which ensures only appropriate data deletion, changes, and amendments can be made. This can prevent data duplication and guarantee data accuracy.

Domain Integrity

Domain integrity is a series of processes that guarantee the accuracy of pieces of data within a domain. A domain is classified by a set of values that a table’s columns are allowed to contain, along with constraints and measures that limit the amount, format, and type of data that can be entered.

User-defined Integrity

User-defined integrity means that rules and constraints around data are created by users to align with their specific requirements. This is usually used when other integrity processes will not safeguard an organization’s data, allowing for the creation of rules that incorporate an organization’s Data Integrity measures.

Types of Integrity Constraints

A set of integrity constraints or rules are followed to implement Data Integrity in a database system. Relational data model suggests the three types of integrity constraints such as domain integrity, entity integrity, & referential integrity.

First of all, Entity integrity denote the concept of a primary key. As per this system, Entity integrity states that every table shall contain a primary key and existing column or columns of the table shall be identified by the primary key & it shall be inimitable and not null.

Concept of a foreign key denote Referential integrity. As per referential integrity rule, any foreign-key value can only be in one of two states. In general condition, foreign-key value refers to a primary key value of some table in the database system. Sporadically, a foreign-key value can be null and this will rest on on the rules of data owner. Under these circumstances, it can be stated here that this relationship is unknown or there is no relationship between the objects represented in the database system.

All columns in a relational database must be stated upon a defined domain is the main concern of the Domain integrity. In the relational data model, the primary unit of data is the data item. This type of data items is known as atomic or non-decomposable. A set of values of the same type is defined as domain. Actual values appearing in the columns of a table are drawn from the Domains which are considered as pools of values.

As the User-defined integrity are set by the specific user with a set of rules which is not related to domain, entity, and referential integrity classes. The database which supports these features, it is the sole responsibility of the database to confirm Data Integrity and reliability model for the data storage & retrieval system. The database which does not support these features then it is the accountability of the applications to confirm Data Integrity though the database supports the consistency model for data storage & recovery process.

A well-controlled single and well managed data-integrity system increases.

[][]Maintainability
=>All Data Integrity administration commences from a single centralized system.

[][]Performance
=>As a single operation unit, all Data Integrity operations perform as consistency model.
[][]Re-usability
=>A single centralized Data Integrity system provides the all applications benefit.
[][]Stability
=>As avoid the multiple system, so Data Integrity operation performs sound as well as better retrieval on a one centralized system.

Examples
Data-integrity mechanism is often considered as the parent-and-child connection of interrelated records. When one or more related child records exist for a parent record then all of referential integrity methods are handled by database itself & inevitably ensures accuracy & integrity of data, so no child record can exist without parent record and subsequently no parent drops their child records. In this system if the parent record owns any child records, then no parent record can be deleted and all of the process handled by the database system.

File systems

File system including Ext, JFS, UFS, XFS, and NTFS or hardware RAID solutions can’t provide satisfactory protection against Data Integrity problems. Some special file system such as BTRFS and ZFS use for silent data corruption can provide extra protection for data integrity. Upon provide this protection and being chance raise to corrupt the data then such file system can construct the data is widely known as end-to-end data protection.

Data Integrity as applied to various industries
[][]FDA has created the draft guidance for Data Integrity system as per 21 CFR Parts 210–212.[12] for pharmaceutical manufacturers. Same guideline has been developed by UK [2015], Switzerland [2016], and Australia [2017].
[][]Data Integrity also addressed by ISO as per ISO 13485, ISO 14155, and ISO 5840.
[][]FINRA [Financial Industry Regulatory Authority], implement the Data Integrity system on 2018 under technology change management policies and procedures” and Treasury securities reviews as Data Integrity problem found in 2017 on automated trading and money movement surveillance systems.

Why Data Integrity Matter?

Now a days Data are becoming more available, a smart business strategy which are using to make decision are obtaining the several times benefits.
According to recent research, a data driven organization is more than 23 times better performer in customer acquisition, nine times more performer to retain their customer and more than 19 times profitable to their competitor.

As the power of data is increasing day by day, so Data Integrity shall be valued properly and its importance can’t be denied at current situation. Presence of any type of error in data can spoil the total organization goal. A data driven organization must protect their database system at any cost to provide better security solution.

Threats involve in Data Integrity

[][]Human error:
It may arise in such case of transferring of data manually from one share drive to another, copying data from one spreadsheet to another and subsequently deleting of row or column of a spreadsheet. Storing data on excel sheet may cause formatting problem during manually data transferring process. Updating of excel sheet from old version to new one may cause formatting problem of subsequent data.

[][]Inappropriate format:
Stored data on Microsoft excel based on cell referencing may not accurate in different format. Failure to determine the same may case Data Integrity problem.

[][]Collection error:
During collecting any type of data, proper precaution shall be taken. Collecting of data on wrong method may cause storing of incomplete data and actual data may not represent the total situation.

[][]Internal security breaches:
If the database system hacked by third part or internal or external competitor may cause serious Data Integrity failure.

Why is Data Integrity Important?

Generally, a specific individual or group of people are involved in database system of a organization. Problem arises when multiple people are responsible to operate the database system. Anyone of the team member may not aware about Data Integrity of the organization, then all of the individual shall educate regarding protection of the database system and tech them the importance of data quality, accuracy, completeness etc. & they must learn how to combat when potential data security threat arises.

If all of the team member are aware about the Data Integrity and know its importance then it is very much effect to maintain the database system.

A better Data Integrity system can save company effort, time as well as valuable overhead cost. Wrong decision may take place based on inappropriate data. Data driven organization always take critical decision based on available data, if Data Integrity of that organization are compromised by any situation, then inappropriate result may arise and the organization suffer in long run.

Data always help to make important decision additionally it protect your company image. If you are collecting your customer information then protect the collect data which you have collect from your individual customer, failure to protect the customer data in proper database system may leak your customer information to another one cause image problem of the company and also mispresent your customer to other party.

Any type of customer information may be tracked and may be asked or run a campaign over them to collect specific target data. All type of collected information may not be sensitive as SSN [Social Security number]. To protect your valuable customer, you have to take a proper step regarding Data Integrity of your existing system.

a company staff always demand to data access to the database to trace any type of data on time manner upon request. He needs to uninterrupted access to the data system. For this reason, Data Integrity is so important for the organization. Data Integrity confirm the traceability & searchability of the data from its mother source.

Effective data accuracy and data protection shall be confirmed to increase Data performance and its stability. It is very much crucial to confirm the completeness & integrity of data. Compromised data always carry the wrong value for the organization & is of no use for most companies.

Same scenario arises for big data management. It is very much important to secure the big data management system as well as to maintain the total database system. All type data is totally worthless Without integrity & accuracy. Your data can be compromised If you fail to do the same. Under this circumstances, awkward & expensive data audit trails shall be mandatory to find out error & recover the total database system.

Most companies have set specific goals for their data & it is now more important than ever. But if integrity is not assured then data is not of much use. If data loss, corrupted or compromised then data can considerably damage any type of business. To maintain it, data security shall be confirmed using proper tools.

Compromised Data is the big challenge to maintain data integrity. There are several ways to compromised the valuable data. Todays almost all of the data are digital and store then in the same than traditional method and its transferred vary rapidly in different places of the globe. So, security shall be considering first & also the collection data is main concert maintain its integrity.

Data can be unaltered if data transferring occur maintaining valid system. Every time Data is moving from one place to another and it is not static, every user of the specific system is using the data and transferring the same in different way.

Management of Data Integrity

A group of steps are available where you can maintain & achieve better Data Integrity for your organization.

Collection of Accurate, Complete, and High-Quality Data

Quality of data depends on the collecting process of the projected data; a collection process is crucial and collection depends on the proper collection method. Failure to select proper data collection technic may cause collection of erroneous data. Sourcing is prerequisite to collect data. Ensure the high-quality data source may provide one step forwards to competitor.

Meticulously Check for Errors

To make common error during collection of data is the main problem of manual collection of error but it can be rectified successfully to involve the second one to the same project. Various type of error can be overcome if proper checking process can be initiate by appropriate body. For most critical data double check or triple check can be initiate. Growing continuous attention during data collection may reduce the data error. Sometime a review of the related data may decrease the data error. A color shading on projected excel sheet in the alternative row may help to track the mentioned data.

Cybersecurity Threats

Most of the time you can’t realize that a hacker or third party is trying to access your database. Person or individual who are trying to control your data send a short link with attractive or recent hot topics or similar to company email address link. Thousand of ways a hacker can try to damage or control your database system, so a strong security system shall be established to protect Data Integrity of the system.

Data Science Course

Failure to know the technical framework of database system, you can’t protect your data properly. If you are capable to handle the system then you need not to collect data science but if you want to update your existing your practice and eagerly want to update your team capability then you can involve your team in any data science course which are already available online which help your organization as well as development of self-confidence.

Devotion to Data Integrity

To keep subjects’ information safe & giving organization’s stakeholders the highest quality, accurate, complete, most data on which to base decisions need daily commitment for your Data integrity. A proper security system and group of trained individuals can support the organization in this situation to continue the company progress.

Data Integrity vs. Data Quality

Data quality is a crucial piece of the Data Integrity puzzle. It enables organizations to meet their data standards and ensure information aligns with their requirements with a variety of processes that measure data age, accuracy, completeness, relevance, and reliability. Data quality goes a step further by implementing processes and rules that govern data entry, storage, and transformation.

Data Integrity vs. Data Security vs. Data Quality

Data security involves protecting data from unauthorized access and preventing data from being corrupted or stolen. Data Integrity is typically a benefit of data security but only refers to data accuracy and validity rather than data protection.

Data Integrity & data security are more relevant to each other. Each of them plays a vital role for each other for their individual achievement. Data Integrity only refers to validation and accuracy of data but didn’t involve to protect data. On the other hand, data security confirms the protection against corruption or unauthorized access.

Data security plays a crucial role to maintain data integrity, on the other hand, Data Integrity is the end result of data security. To maintain data integrity, data security is the vital point and this situation may arise when accidental compromise occurs for data integrity.

Data Integrity is the essential component for the modern business procedure while making decision based on accuracy and efficiency of database. The main focus of the data security leads to Data Integrity and various type of procedure are applied to achieve the same.

Data quality can be defined that the data stored in database is compliant with the organization’s standards & requirements. It maintains integrity in a database. A set of rules to a specific or whole dataset and stores it in the target database shall be implement to do the same. Data Integrity shall be considered as data accuracy as well as correctness of data.

How to Protect Your data?

Validate Input

To ensure data accuracy data entry must be validated & verified input is significant when data is provided by familiar or unfamiliar sources, such as end-users, applications, & malicious users.

Remove Duplicate Data

Sensitive data stored in secure databases cannot be duplicated & it important to ensure that publicly available spreadsheets, emails, documents, & folders. To prevent unauthorized access to business-critical data or personally identifiable information duplicate shall be remove as soon as possible with the help of authorized personnel.

Back Up Data

To confirm data security & integrity data backups are crucial. To prevent the valuable data from permanent lost data backup shall be perform on regular manner at the end of everyday work. Organizations that suffer ransomware attacks, Data backups are especially important for them to protect their potential resources.

Access Controls

To maintaining data integrity, appropriate access controls shall be introduced in the organization. Data privileged option shall be implemented for specific user to control the database access procedure. This process will help the user understand their limitation to use the database system as well as to maintain the whole system.

Audit Trail

An audit trail is the standard practice to trace the unfavorable event. Data breach may occur at anytime in a renowned organization. If audit trail facility are available for the organization then it is very much to find out when and how data breached where. If proper information is available then it is easy to trac the source of attack. So audit shall be introduce at your organization for your database management system.

Assurance of Data Quality

It is the part of the Data Integrity process. Regular shall be conduct so that data can meet the certain standard. The processes of data accessibility, data cleaning, , data standardization is the main concern of the Data quality assurance. Data cleaning deal with inputting missing data, removing invalid entries, update same on timely manner.

Data accessibility deal with availability of the data to the stakeholders in secure and appropriate manner. For encoding and entering data, business shall be maintained and unauthorized data entry or transfer shall be prohibited. All type of company rule shall be implemented increase of transfer access of data to potential sector.

Data Corruption vs Data Integrity

Data corruption shall be considered as the serious Data Integrity failure. Based on the current practice, data corruption may be occurred through multiple channels. Most of them a very common problem is human error occur during collection or transferring of data. Malware and physical damage are another potential cause of data corruption.

Most human error often cause in wrong entry of collected data, unauthorized entry of database system, involving newcomer to sensitive practice with our prior training, programming etc.

It can be traced with appropriate data validation checks & restricting access to database system. Extensive & systematic use of backups can support restore databases in case of improper data entries.

Malware is another common cause of data corruption and this is basically occurred from external source which main purpose is to stole the data from potential data server. Cyberattacks are almost always unpredicted and instantly can’t recognized the source on the most of the cases. So here come the data encryption, always try to encrypt the critical and sensitive data and if possible tight security system shall be introduced though cost may be high to do the same.

To ensure organizational network security, regular penetration testing shall be done, this will help you to secure the organizational network system. A physical damage is may cause the data lose which mainly cause by accident and disasters. To protect data, data may be store in different physical location will protect from accident and natural disasters.

Data Integrity and Why Is It So Important? Read More »

What is the difference between affect and effect?

Affect & Effect

These two words are verbs & nouns and their meanings overlap. It is not possible that whose word come first in English language. In general, Affect is used as Verb and effect as a Noun.

Meaning of Affect

[][]Affect means Change in something, to act on.
“The hot weather affected the iceberg.”[The hot weather produced a change in the iceberg.]

[][]To amaze the mind or move the feelings of,”
“Billie Eilish song ‘lovely’ deeply affected her.” [The music changed his moods or thoughts].

[][]You can also change the word Affect with Right word
“The hot weather damage the iceberg.”
“Billie Eilish song ‘lovely’ deeply moved her.”

To express a change or to describe an action, the word “Affect” shall be use.

Meaning of Effect

Effect means “result” or “consequence.” & Most commonly used as a noun. Effect can be replace with another noun.

“His high market share value was an effect of ownership change of the company” Another way to say it is, “His high market share value was a result of ownership change of the company”

Remember Difference Between Affect & Effect

[][]Memorize the word RAVEN; you can easily differentiate them_

R = Remember
A = Affect is a
V = Verb
E = Effect is a
N = Noun

There is another way to remember when to use affect and effect:
[][]A is for action (affect); E is for end result (effect).

Example

Affect

[][]Almost always used as a verb to mean to influence someone or something.

How does one’s creativity affect success on the project?
These songs will affect the number of people who will come to the outdoor concert.

[][]Affect can be used as a noun in one particular situation.
The old man’s facial expressions had a humorous affect.

Effect

[][]Most often used as a noun. It denotes an event or a thing. Often used when result is being discussed.

What effect did the job of company on his family?
Did his sudden retirement have any effect on his family?

[][]Effect can words like : on, the, any, into, , take, an, or.
The prescribed pill had an effect on the patient’s symptoms.
We have to consider the changes time to take effect.

[][]Effect can be used as a verb in one particular situation.
The new management is responsible to effect negative changes in the office.

What is the difference between affect and effect? Read More »

What is the difference between Data and Information?

Most of the cases we think that “data” and “information” are same but they actually aren’t the same though they are often used interchangeably. There are elusive differences between these two components & their purposes of use. information is organization & interpretation of group of facts where Data is defined as individual facts. To identify and solve problems, you can use the data & information together. To drive a successful business, we can use these two components to accelerate the ultimate mission to reach the goal.

What Is Data?

Collection of individual facts or statistics is defined as data (Data is plural form of ”datum” but the term didn’t use in for daily expression. Data has its various type of form such as figures, text, observations, numbers, images, graphs, or symbols. Individual dates, prices, weights, addresses, ages, temperatures, distances, names, etc. can the example of data.

Data is simply defined as “facts & figures”. Each piece of data is a tiny fact that doesn’t mean abundant of its own. Data can be defined for singular fact or collection of facts. It comes from the Latin word ”datum”, mean “something given”. “datum” is technically correct singular form of data but is hardly used in public language. Its early usage dates back to 1600s. Over time “data” has become plural of “datum”.

Data doesn’t carry any significance or purpose, it’s the raw form of knowledge. To make it meaningful you have to interpret data. Bits & bytes are used to measured data which are units of information in context of computer storage & processing the same.

Data without analyzed, organized, and interpreted may even seem useless & data can be simple. Two types of data are depicted here-
[][]Quantitative data is in numerical form, like volume, weight, cost of an item. Its not descriptive.
[][]Qualitative data is descriptive, like sex, name, or cloth color of a person. It’s not but non-numerical.

What Is Information?

It can be defined as act of knowledge gaining process through research, study, communication, or instruction. Information is the totality of group of analyzed and interpreting data. A data is always the individual numbers, figures, or graphs whereas information is considering the perception of those items. In this era, we can mention that most of the sophisticated modern industry always maintain environmental monitoring through recording of Temperature & Relative Humidity, through out the year of the year and achieve it in a suitable position.

Information can be defined as “news or knowledge received or given”. Processed, interpreted & organized facts is information. It comes from the Latin word īnfōrmātiō, mean “formation or conception.”

This type of recoding doesn’t bear any significant meaning but if you organize, analyze the recoded data then you can easily realize the Environmental condition changes in specific season. You can trend the data to sort out the best matching, minimum maximum data etc. which useful to set up or install the best quality BMS [Building Management System] parameter. Without analyzing and organizing the data, it is the just piece of recording doesn’t denote any significant value. A well-organized data can help the others.

In basic terms, it can be concluded that data is unorganized explanation of raw facts from which information can be take out.

Significant Differences Between Data vs Information

[][]collection of facts is considered as Data where information puts all of those facts into context.
[][]Data is always raw & unorganized where information is processed and organized.
[][]Data points are individual & most of the time it is unrelated. Information relates these points and show the actual behind it.
[][]Without analyzed and interpretation data is totally meaningless, when it organized then it became meaningful information.
[][]Data is always independent but Information depends on data due to you can’t get any information without processing data.
[][]Numbers, graphs, figures, or statistics is the form of data. Information generally appears as language, words, thoughts, ideas etc.
[][]To base on data, you can’t make any decision but when information available at your hand you can make any decision. So, data are not enough to make any decision, information require to do the same.
[][]Data always defines figures & facts. It comprises of one entry or collection of diverse values. Information defines values & context together, resulting in approximately meaningful. It forms an organized & interconnected structure, from data, to interpret or link the whole.

[][]Example
=>For data examples, we can use Lance, M. Kiely, 4590 Neville Street, Terre Haute, IN 47807. The separator [commas] characterize each distinct fact that may or may not be linked to others.
=>In this example of information, Each fact narrates to other facts to form a concept, known as Lance M. Kiely. Creating this Lance M. Kiely entity allows people to reason, calculate, & do other influences.
Lance M. Kiely
4590 Neville Street
Terre Haute, IN 47807

Data vs. Information in Computers

If we consider computers, Data can be considered as INPUT on anything that instruct to computer to do or store. The OUTPUT of the computer which exhibit your computer after your instruction to computer.

As per statistics, data defined as raw information but term statistics is often used in place of information. Statistics interpret & summarize data.
In business, data are often raw numbers & information is a collection of separate data points which you use to realize what you’ve restrained.

[][]1.0
Data: typing the words “Dog videos” in your computer web search engine (INPUT).
Information: The list of search results which includes a variability of dog videos on the resulted browser page (OUTPUT).

[][]2.0
Data: 9994565566
Information: phone number (555)456-5566 of a person.

[][]3.0
Data: 46.07 & 789
Information: Molar mass & Density of Ethanol in g/mol & kg/m³

[][]4.0
Data: 70%
Information: Isopropyl alcohol in percentage

[][]5.0
Data: -16
Information: Freezing points of Vodka in Fahrenheit

Difference Between Data and Information

ParametersDataInformation
ContentUnrefined raw factors.Refined in a meaningful way.
CharacteristicData is considered property of a specific organization & is not offered for sale in the public.Information is offered for sale to public.
Decision MakingRaw data is insufficient to make any decision.Information is enough to make any decision.
DependencyData depends upon the sources for collecting method.Information always depends upon data.
Design of Data Data is never designed for specific need of user.Information is always explicit to requirements & expectations because all extraneous facts & figures are detached, during transformation process.
Dependency levelData never depends on Information.Information constantly depended on Data.
DescriptionHelps to develop ideas or conclusions based on Qualitative or Quantitative Variables.It is group of data which carries news and meaning.
EtymologyData has comes from Latin word, datum, means “To give something.” The word “data” become plural of datum.It comes from the Latin word īnfōrmātiō, mean “formation or conception.”
Example1.0 During word Tour Ticket sales on a specific Band.1.0 Sales report generate by region & venue gives information which venue perform best.
Example2.0 An example of data is a student’s Eye Color.2.0 The average Eye Color of a class is the information derived from the given data.
FormatData found in the form of letters, numbers, or a set of characters.Ideas and inferences
FeatureData is a single unit & raw. It doesn’t have any meaning alone.Information is artefact & group of data which jointly carry a logical meaning.
InterrelationCollected Information.Processed Information.
Knowledge levelLow-level of knowledge.Second level of knowledge.
MeaningData does not have any definite persistence.It conveys meaning that has been allocated by interpreting data.
Measuring unitMeasured in bits & bytes.Measured in different meaningful unit like time, quantity, etc.
Meaning of baseData is based on records & explanations and, which are deposited in computers or remembered by a individual.Information is considered more consistent than data. It helps investigator to conduct a appropriate analysis.
Support for Decision makingData can’t be used for decision makingIt is extensively used for decision making.
SignificanceData collected by the researcher, may or may not be useful in different situation.Information is useful & appreciated as it is readily accessible to the researcher for use.

List of Examples of Data vs Information

differences between data and information, how these examples turn data into insights:

[][]An individual customer’s bill amount is data at a specific restaurant but after a certain period of time or after one day collection when the restaurant Manager or owner collect all the customer bill of that day or time, it can produce valuable information of the restaurant as it can produce which item of the restaurant is hot cake or what item is running well and what are not. After that the restaurant, can realize how they can maintain the inventory of a specific item and how to continue their service as well as to minimize the overhead, wadges, supplies etc.

[][]An individual customer service survey of a restaurant is a data but after a period of time when compile the all the survey, then it can produce valuable data regarding area of improvement of the restaurant such as customer service, price, cleaning, mannerism, hospitality, space, location, viewpoint etc.

[][]A single social media like on a media post is a data but when multiple social media item like comments, share, statistics etc. are compiled then the specific company can focus on the specific social media where they are performing best and where they are in worst condition. Comments from a social post of multiple social media is very useful to do the same. It helps the company to set their goal based on the comments collect from customer and it help to find out multiple idea from multiple customers.

[][]On their own, inventory levels are data. However, when companies analyze and interpret that data over a range of time, they can pinpoint supply chain issues and enhance the efficiency of their systems.

[][]Inventory management of the company for the different item is the data but when it collects for certain period of time it can be valuable information regarding the inventory item which can help the supply chain management system to run their activity appropriately.

[][]A Price of a specific item is a valuable data but when processing the data from multiple company can produce valuable information regarding market gap, advantage of the competitor, profit margin, bonus, discount, policy etc. for the specific item.

[][]Taste of Azithromycin Suspension is a data but when you collect different taste from different company product you can produce valuable information regarding taste that which taste is more acceptable to the end user i.e., mango/orange/strawberry/pineapple etc. from this activity you can collect valuable information and implement the same for your company product.

[][]Temperature readings all over the world for the past 10 years can be consider as data. When this data is organized, analyzed to find out global temperature condition is raising over the period of time, then this data changed to information.

[][]Number of visitors to a specific website by country of the word is an example of data. Finding out that the traffic source from Canada is decreasing while that from Austria is increasing is meaningful information.

[][]Often data essential to back up a claim or supposition consequent or inferred from it. Such as before a drug is approved by FDA, manufacturer must conduct clinical trials & must have submit lot of data to reveal that the drug is safe.

“Misleading” Data

[][]Due to the processing of data, interpreted & analyzed, this is very possible that it can be interpreted incorrectly. When this leads to specious conclusions, it can be said that data are misleading. Often this is the consequence of imperfect data or a lack of framework. Such as your investment in a mutual fund may be up by 7% & you may accomplish that fund managers did a great job. Nevertheless, this could be misleading if major stock market indices are up by 10%. In this case, the fund has floundered the market pointedly.

[][]In the year of 2007, Famous toothpaste company Colgate ran an ad campaign & stating that 80% of the dentists recommend Colgate Toothpaste for safe dental health. From this promotion, many consumers assumed that Colgate was the best choice for their safe dental health for daily use. But in practical, this wasn’t inevitably true. In reality, this is the well-known example of misleading data & information.

[][]Anchor Tucker Carlson presented a graph saying, number of Americans recognizing as Christians had distorted over last decade during one of Fox News’s broadcasts. Over the image above, a graph showing in 2009, Christian Americans is 77%, number decreased to 65% in the year of 2019. Now, if issue here is not noticeable enough, here the Y-axis in that chart starts from 58% & ends at 78%, making the 12% drop from 2009 to 2019 look way more substantial than it really is.
Sample size is the vital point to make any key decision for the organization. Making any decision data collected from 100 sample is more accurate data collect from 10,000 sample. Data collect from 100 sample is misleading compare to 10,000. A key decision shall be make from vast amount of sample.

[][]Federal Trade Commission (FTC) filed a lawsuit against car company Volkswagen , which claimed that car company had betrayed customers with advertising campaign it used to promote its allegedly “Clean Diesel” vehicles, according to a press release.

In the year of 2015, it was uncovered that Volkswagen had been cheating emissions tests for its diesel cars in US in the past 7 years. The Federal Trade Commission, alleged that “Volkswagen cheated consumers by selling or leasing more than 550,000 diesel cars based on the false claims that cars were low-emission & environmentally friendly.” For their false claim, the company was remarkably fine up to $61 billion for the violation of Clean Air Act.

[][]Red Bull, Energy drinks company was sued in 2014 their slogan “Red Bull gives you wings.” The company settled case by agreeing to pay out maximum of $13 million — including giving $10 to every US consumer who had bought their drink since 2002.

They claim that the caffeinated drink could improve consumer’s concentration & reaction speed; the tagline company use for last two decade went alongside marketing claims. One of the regular customers of Red Bull drink claim that that he had not developed “wings,” or shown any signs of enhanced intellectual or physical capabilities.

[][]In 2010, Kellogg’s widespread Rice Krispies cereal had a crisis when it was defendant of misleading consumers about product’s immunity-boosting properties. The Federal Trade Commission [FTC] ordered Kellogg to close all advertising which claimed, cereal enhanced a child’s immunity with “25 percent Daily Value of Antioxidants and Nutrients -Vitamins A, B, C and E,” affirming the claims were “dubious.”

[][]New Balance, the famous show making company [Owner, Jim Davis, own almost 95% total share of this company] was defendant of false advertising in 2011 over a sneaker range which claimed that it could help wearers to burn calories but it was subsequently found that there were no health assistances from wearing this sneaker range. From New Balance, they explain that using hidden board technology & it was advertised as calorie burners which activated the quads, glutes, hamstrings & calves. New Balance agreed to pay a settlement of $2.3 million on August 20, 2012.

How Businesses Can Leverage Data & Information

Is it come to the point to distinction between data vs information really matter for businesses? If any company that company collect accurate data then interpreting it and generate information and implement the same on right time on right place can realize the actual benefit for the company.
For example, a company might gather data about the performance of their ads or content. Running a successful add or content to the various platform can produce valuable data. From the data they can produce right information regarding product design, brochure generation, promotional activity, product awareness, customer demand and customer buying capacity.

This can also help to develop target customer, future offering, promotion, branding and developing multiple products for the company.
Right data can lead the organization to the right goal but to maintain the right set of data is very difficult. There are several blockades to create a data dependent better smart organizational culture. Different team of an organization may collect & maintain disparate sets of information. Hence a central database system is crucially need for the organization. Without a central database system, none one can earn the actual benefit and interpretation of data may fail. Data need to supervise by someone, without proper supervision data may not maintain its proper quality and generate poor data mislead the organization.

Any business depends on expressive data patterns to get information. There are dissimilarities between data and information. Business relies on meaningful data patterns to get information, in this article let’s explore the differences and similarities between data and information. Misinterpretation the difference between “data” & “information” sets up the stage for slip-ups. Like the six blind men in an Indian legend, trying to define an elephant, end up puzzling discrete facts, or data, as information or meaning.

In six blind men’s dilemma, individually complicates data (trunk or legs) for information (an elephant is like giant cow or an elephant is like a giant snake). Likewise, anyone can collect customer data & think they have the full customer information when they are actually not. Data & Information have specific implementation. To correctly recognize & use either one, you need to understand the change between data & information is.

To create an effective data driven organization, then you need to maintain the data source which must available across the group of qualified people who are technically sound to generate information from processed data maintaining appropriate protocol to assure the proper data quality.
Data is very critical to generate information and both these two items is crucial to make any decision for the organization.

DIKW [Data Information Knowledge Wisdom] Model

DIKW is the model used for discussion of data, information, knowledge, wisdom & their interrelationships. It denote functional or structural relationships between data, information, knowledge & wisdom.

Are data and information the same thing?

Data is based on observation & records which frequently store in computers or simply memorize it by individual. On the other hand, information denotes to be more consistent than data. In other words, it is a proper analysis which researchers or investigators conduct for converting data into information.

Data and information may be the same thing, From a content & format perspective. For example, you can point same values in two diverse columns on a spreadsheet. Nevertheless, data & information contents & formats do not have to match. In any case, you use data & information very in a different way.
If you want to sort out the value “New York, United States” You will filter data named “New York” under city and “United States” under country.

On the same spreadsheet, If you want to know if the Lance M. Kiely records mean the identical person. Then look at the information in both rows & see, across the columns:
Lance M. Kiely
4590 Neville Street
Terre Haute, IN 47807
You determine both Lance M. Kiely, living in New York, United States, mean the same customer thing from the information provided.

How do data and information differ?

Though Data & information may have the same values but from the creation & business usage they may differ. Data generally includes entries whereas Information contains context. Information comprise data with different contents & formats & be the same thing.

As per data perspective point, “United States,” “UNITED STATES,” and “U.S.A.” represent entirely different facts based on number of characters & formatting varies. Therefore, Lance M. Kiely, who lives in U.S.A., is not same customer as Lance M. Kiely, who lives in United States.

If we consider information viewing platform, the “United States,” “UNITED STATES,” & “U.S.A.” represent the same thing for geographical reason because someone with understanding of geography can point to the “United States” or the “U.S.A.” on a American Map.

The correct data and accompanying context make the United States and the U.S.A. contain meaning about a shared concept of that region, like culture, sports, and government. From the shared concept of that region, like culture, sports, and government make the data more accurate. Lance M. Kiely, who lives in U.S.A., with Lance M. Kiely lives in the United States, and consider creating the same object. Comparing with the other people lives in United States using additional data points like cultural activities in U.K.

Frequently Asked Questions

What is data? Explain with example.

Raw, unorganized, unprocessed facts are known as Data. All of the facts consider as data until it processed, organized such as all information writing on the paper is data until its processed & organized in suitable manner.

What is information?

Processed, organized data which is advantageous in providing useful facts is known as Information. For Ex. It can be concluded that if data are processed and organized in right way generate valuable piece of information.

What is valid information?

A reliable fact is considered as Valid information. Checked & verified information that is ready for use in a specific purpose.

What is the classification of Data?

Classification of Data

Data classification is a critical element of any information security & compliance program, especially if any organization stores big volumes of data. To understand the data security strategy, classification of data plays an important role providing information that where the sensitive data shall be stored. It provides valuable information regarding unused data & elimination of the same type reduce the maintenance cost for the organization.

Types of Data Classification

[][]Content-based classification inspects & interprets files to classify sensitive information.
[][]Context-based classification looks at location, application, creator tags & other variables as secondary indicators of subtle information.
[][]User-based classification depends on manual selection of each document by an individual.

Basic Classification Scheme

The modest scheme is three-level classification:

[][]Public data
Data that can be freely revealed to the public. Examples include any company contact information & any browser cookie policy.

[][]Internal data
Data that has low security level but is not for public expose, like marketing research for a product.

[][]Restricted data
Highly subtle internal data. Expose to public platform create negative impact on operations and put the company at financial or legal risk. Restricted data entails the highest level of security protection at any cost.

Government Classification Scheme

Government agencies use three levels of sensitivity as top secret, secret and public but based on situation can be classified into five types

[][]Top secret-Cryptologic & communications intelligence
[][]Secret-Selected military plans
[][]Confidential-Data signifying the strength of ground forces
[][]Classified-Data labelled “For Official Use Only”
[][]Unclassified-Data that may be publicly released after authorization of respective body.

Commercial Classification

Typically, organizations that store & process commercial data use 4 levels to classify data: 3 private levels and one public level.

[][]Sensitive- Intellectual property, Secrete Formulation, PHI
[][]Confidential-Vendor contracts, employee reviews, Contract, Special Allowance
[][]Private-Customer names or images, Sensitive Video promotion
[][]Proprietary-Organizational processes, Quality System
[][]Public-Information that may be disclosed to anyone

What is the meaning of the two types of data?

The two types of data are qualitative & quantitative. Qualitative data is non-numerical data like eye color, skin texture, Hair color, Shoe color, Clothing color and more. On the other hand, quantitative data is in the form of numbers like the weight of books, number of apples, number bird and more.

What is the difference between Data and Information? Read More »

Forced Degradation Study or Stress Testing Procedure

What is Degradation?

Forced Degradation Study before proceeding on it ,first of all  ”Degradation’‘ to be discuss first, This is the act of lowering to some degree or someone to a less respected state or position. A CEO of a multinational company resigning from his office is a degradation. It’s also a downcast state.

The word degradation is very much related to the degrade, which comes from Latin word Degradare. The word “Degradare” comes from “de”-, meaning “down,” & gradus, meaning “Step.” So, it is very much clear that the degradation as a step down, or feeling as though you’re a step below.

Degradation products

It is the unwanted chemicals which can generate during manufacturing, transportation & storage of pharmaceutical drug products & can affect efficacy of pharmaceutical drug products. A small amounts of pharmaceutical degradation products can affect crucial safety because of the potential to cause adverse effects in end user.

Subsequently, it is crucial to focus on formulation, storage conditions, transportation, distribution channel and packaging to prevent the formation of degradation products which can negatively affect quality, safety and efficacy of the pharmaceutical drug products.

To find out the main cause of degradation of the pharmaceutical product is the crucial point, various software and data tracking system can help in this matter. This system can provide useful information during transportation and storage of pharmaceutical products, the route shall be determined to estimate the main cause.

Presence of a genotoxic degradation product shall tend to more assessment if it identified on due time. The chemical structure of the substance shall be determined to identify the toxic alerting structures associated toxic products, products [Compound] without active structure is marked as ordinary impurities.

A risk/benefit analysis shall be done to evaluate the levels of degradation products and most of the nest pharmaceutical call its mandatory. During the development of any type of product either critical or non-critical drug, critical variable of the drug products shall be follow-up which will control the degree of degradation of impurities.

Now a days the impurity profile has been considered as the key point of the product quality. It is the essential part of the quality parameter for the various competent regulatory authority. The toxicological evaluation and impurity profile become the key point of the degradation products to confirm its certain level of efficacy. Various types of test method have been identified to investigate the degradation products, all of them assay method consider the best to all and it’s highlighted to prove its effectivity.

The purity, safety and efficacy of the product depend on the stability of the product and it is the critical parameter of all the parameter. A product must be stable at a certain period of time to prove its efficacy, potency and safety.

A less stable or changes of stability can create serious toxicological effect by forming toxic degradation products and deliver less active or less effective or less potent drugs to the end user. Under these circumstances, this is very crucial to known the actual behavior of the drug products in various surrounding or environmental conditions.

Dissolution test are considering the most quality control tool for the commercial batch to batch product to monitor its consistency over a certain period of time. It also provides significant information during post approval changes of the certain product as changes made in formulation, manufacturing process and different scale up procedure.

To confirm the quality, safety and efficacy, the chemical stability is very important for a pharmaceutical product. This is very important to know the environmental influences of a certain developed product in specific condition such as Heat [Temperature], Humidity [Relative Humidity] & Light [Photostability] and this also regulatory [ICH & FDA] requirements.

Data acquire from stability study denote the shelf life and storage condition of the specific tested drugs, the container closure system [Protective packaging system] also require to satisfy the regulatory expectation.

Different types of method/instruments are available to determine the degradant compounds which are readily present during the forced degradation study period. HPLC-UV [HPLC with UV detector] and HPLC-PDA [ HPLC with Photodiode Array Detector] is the renowned method and extensively used in pharmaceutical company at the time of degradation study and validation and development of various type of method.

LC-MS [HPLC with Mass Detector], GC-MS [Gas Chromatography with Mass Detector] and NMR [Nuclear Magnetic Resonance] spectroscopy are significant methods to detect the degradants’ structure.

What is Forced Degradation Study?

Exposure of specific sample at the unfavorable/stress condition of Heat [Temperature], Humidity [Relative Humidity], Light [Photostability], Oxidation and Acidic/Basic condition; observe/detect the changes of those sample or measure the rate of changes/degradation, mainly in Efficacy, Safety and Potency parameter of drug substance. Forced degradation study is the key point during the development of a specific drug. Determination of the type changes denote the modification or changes of the development process.

Now a days Force Degradation Study become the prerequisite to submit the NDA to regulatory authority and it became the quality parameter for the new product. During the regulatory submission, the Force Degradation Study data shall be submitted to get satisfactory result from FDA. Some of the best application of Force Degradation Study is depicted here-

[][]Developing and validating stability study indicating method as per regulatory guidelines [ICH Guidelines].
[][]To set up specification of degradants or impurities and to identify structure and toxicity.
[][]To set propose shelf life the specific product without performing Realtime stability data.
[][]To avoid incompatibility of drug products and excipients.
[][]Determination of the process related degradation products or impurities.
[][]Provide supporting data to lab investigations/OOS [out-of-specification] analysis.
[][]To provide regulatory compliance documents during submitting of ANDA/NDA to FDA.

It is a useful tool to predict the stability of any Active Pharmaceutical Ingredient (API) or formulation product. It helps to know about the impurities developed during the storage of drug products in various environmental conditions.

Forced degradation is performed by applying artificial methods and a drug is degraded forcefully. It is also known as stress testing. To assume the stability condition of API [Active Pharmaceutical Ingredient] and formulated product Forced degradation study plays an important role. It also helps to identify the impurities generated during storage of drug products in different environment stage.

Why Forced degradation study carried out?

Its play a vital role to develop and validating of stability study signifying method. At the time of developing phase of a new drug product, force degradation study performs to determine the degradation pathways of drug products & drug substances. It is very important to determine impurities of the degradant product, Forced degradation study quantify the number of impurities present on the specific drug substance. It helps to determine the molecular chemistry. Forced degradation study assure the more stable product. Help to develop the degradation profile. Stability related problem can be solved through Forced degradation study. Forced degradation study also highlight the following point of view-

[][]Evaluation of drug products & drug substance in solution.
[][]Determination of structural transformation of drug product & drug substance.
[][]Determination of the concentration of the degradation products.
[][]To identify the non-relevant impurities in the existence of the desired product.
[][]Separation of the product related degradants derived from intact placebo & excipients.
[][]Describe the degradation pathways of the specific drug substance.
[][]To categorize the degradation products which generate spontaneously during storage & use of products.
[][]To generate product related variants & develop analytical methods Forced degradation studies are performed during accelerated and long-term studies.

During the Forced degradation study, the degradation products may or may not be generate but it will show the degradation pathway of the product. This process will help them develop the analytical method of the relevant product and stability indicating analytical procedure. If any degradation occurs during performing of Forced degradation study, the degradation product shall be evaluated if it significant or minute, to robust the developed formulation.

How Forced degradation Study Conducted?

This study of the drug products or substances is generally conducted on the solid and solution stages at the high temperature exceeding accelerated stability condition which is above 40°C. Various condition are consider here as oxidation, hydrolysis, photolysis, polymerization and thermolysis. In Solution hydrolysis condition are investigated in broader pH range and in solid stage high relative humidity taken under consideration.

Control exposure of molecular oxygen or addition of oxidizing agents such as peroxides is use during investigating Oxidation in solution.
Applying heat in solid state effects of thermolysis are usually assessed. Light with wavelengths in the 300-800 nm range are use in Photolysis investigation in solution or the solid state. In an oxygen atmosphere photooxidation can be investigated with light under oxygen atmosphere. Measuring the rate of degradation, Drug substance polymerization can be investigated at the various drug substance concentrations in solution.

List of Analytical Tools to perform Separation & Identification of degradant

A. Sophisticated Techniques

[][]Capillary Electrophoresis- Mass Spectrometry [CE-MS].
[][]Gas chromatography–mass spectrometry [GC-MS].
[][]Liquid chromatography–mass spectrometry [LC-MS].
[][]Liquid Chromatography- Nuclear magnetic Resonance [LC-NMR].
[][]Liquid chromatography-Fourier Transfer Infrared [LC-FTIR].

B. Conservative Techniques:

[][]Thin layer chromatography [TLC].
[][]Solid phase extraction [SPE].
[][]Accelerated solvent extraction [ASE].
[][]Low-pressure LC [LPLC].
[][]Supercritical fluid extraction [SFE].
[][]Mass Spectrometry [MS].
[][]Nuclear Magnetic Resonance [NMR].
[][]High Performance Liquid Chromatography [HPLC].

Extend of degradation

For validation of a chromatographic purity assay, degradation level of 10-15% is adequate to perform the activities. Forced degradation studies are not considered part of the formal stability program though forced degradation studies are a regulatory requirement & scientific necessity during development of a specific product. For conducting studies at the various phases of development the guidance gives various recommendations.

Selection of Forced Degradation Condition

In common industry practice, forced degradation is generally performed in different stress conditions, i.e., thermal, acid, alkali, peroxide, and UV, along with a control sample which also comply with ICH guidelines. There no specific range or rate of degradation in current industry practice but 5 to 30 percent degradation shall be taken into consideration and this can be achievable on any one of the above stress conditions.

Through stress testing, the aim of the degradation to be achieved to implement the control room temperature for the stability conditions. The conditions or concentrations of reagent shall be optimized if higher or lower degradations are observed.

During the degradation study Mass balance shall be demonstrated & it shall be around 100%, taking into attention margins of analytical errors. During mass balance evaluations, all the degradants /impurities must be calculated.

Any batch which is not be the part of regulatory submission can be used for the forced degradation study. For multiple strengths of the same placebos and different amounts, the highest ratio of placebo vs. API [Active pharmaceutical ingredient] shall be use.

Forced degradation of all the strengths shall demonstrate if placebos are different. Placebo & API [Active Pharmaceutical Ingredient] must be demonstrated to identify actual degradation pathways during the drug product force degradation study. All the placebos shall be considered for force degradation study if placebos are different for different strengths of drug product.

Various degradation conditions are depicted on the following table which is accepted by the regulatory authority [FDA] at the time of DMF/ANDA/NDA submission-

Degradation TypeReagent ConcentrationConditions to be appliedTimeRemarks
Acid5N HCL80deg.C1 HourConcentration, condition and time can change to optimize degradation
Alkali5N NaOH80deg.C1 HourDo
Peroxide10% H2O280deg.C1 HourDo
Heat/Thermal80deg.C80deg.C1 HourDo
UVExpose under UV light at 254nm wavelengthAmbient Temperature24 HoursTime can change to optimize degradation
ControlN/AN/AN/AN/A

Force Degradation shall be performed in solid or solution form though it is recommended that Force Degradation shall be executed in solution form using the mobile phase/diluent to get a homogeneous effect with better result. Force Degradation studies shall be started with harsh conditions (i.e., high temperature with high concentration of reagent) to shorten time of study.

Milder conditions shall be applied by reducing concentration of reagent with lowering temperature, etc. when degradation found 30% or above. Based on the initial degradation outcome, Degradation conditions can be optimized to achieve a target range.

To extend shelf life of chromatographic column, pH shall be adjusted about 7.0 for acid & alkali degradation. Different reagents & conditions shall be applied, e.g., Zn, H2SO4, etc. If degradation did not find in any of above conditions. A few numbers of molecule designated rock stable molecules as these molecules didn’t degrade any of the above stress condition. During a stability study This kind of molecule will not engender any additional impurities/degradant peaks.

If drug substance or product shows stability for two years at 30 ±2⁰C & 65 ±5% RH & Six months at 40 ±2⁰C & 75 ±5%RH, then the drug substance or product declared stable.
Concentration of the drug that is being tested for the degradation is a great point. For the degradation study 1 mg/ml of drug concentration is recommended though some degradation studies are done at concentration of drug in the final product. Main cause for this type of study is that precise amount of the degradation can be found in final product & their impact can be scrutinized.

Factors Affecting Forced Degradation Studies

Hydrolytic Degradation:

The reaction of chemical with water at different pH values occur in Hydrolysis degradation. In this degradation drug react with water in acidic & basic conditions. According to the stability of the drug substance concentration of the acid or base is selected where pH is 0.1 to 1.0 M HCl [Hydrochloric Acid] or H2SO4[Sulfuric Acid].

HCl & H2SO4 is used to maintain acidic conditions and 0.1 to 1.0M NaOH [Sodium hydroxide] or KOH [Potassium Hydroxide] used to generate basic conditions. Some materials are not readily dissolve/soluble in water freely; in that case other solvent are use to dissolve the water insoluble materials. Solvent shall be selected carefully so that it can’t degrade the selected drug substance.

Descriptive termPart of the solvent require per part of solute
Very solubleLess than 1
Free SolubleFrom 1 to 10
SolubleFrom 10 to 30
Sparingly solubleFrom 30 to 100
Slightly solubleFrom 100 to 1000
Very Slightly solubleFrom 1000 to 10,000
Practically insoluble10,000 and over

Reference: British Pharmacopoeia [BP]

Generally Chemical degradation shall be conduct in room temperature but if no sign of Chemical degradation occur at room temperature then room temperature shall be increase up to 50-60 ⁰C. A seven days timeframe shall be selected to perform the study. To prevent further degradation, Chemical degradation should be terminated using acid, base or buffer solution. Chemical analysis shall be done as soon as possible after completion of the test.

Oxidation Degradation:

in the forced degradation study, H2O2 (Hydrogen peroxide) is a widely used oxidizing agent. Hydrogen peroxide at 0.1% to3.0% solution is used at room temperature for 7 days is the suitable range to perform the activities. When more then20% degradation occur for a certain product, it can be considered abnormal cases.

Photolytic Degradation:

To determine the effect of light on the product during storage in the market Photostability testing of any drug take into consideration. light conditions shall be described during photostability. light source shall be cool white fluorescent lamp & wavelength of light shall be 200-800 nm (UV+ visible) which is also comply ICH guideline. The and the light intensity shall be not less than 200 watt-hours per sq meter and exposure time shall be not less than 1.2 million lux hours. To monitor the condition, a calibrated lux meter shall be use in place.

Result of forced degradation studies

[][]Forced degradation studies help to determine_
[][]Likely/Probable degradants
[][]Degradation paths
[][]Inherent stability of the drug molecule
[][]Validated stability indicating analytical method

When forced degradation studies to be performed?

This is the best practice to perform forced degradation studies at the time of development of new drug substance and new drug product. FDA prefer to perform it at phase III of the regulatory submission which is the best time to do the same. To establish the regular stability study, forced degradation studies can be prerequisite. This study can be done in different pH solution in the presence of light & Oxygen with high temperature & Humidity Level.

Generally, degradation study performs on single batch. There are two types of timeframes are use to perform stability study which Long Term [12 Months] & Short Term [6 Months]. 6 Months are performed at accelerated condition. Moreover, Intermediate Stability Study performed in a condition lesser than accelerated condition.

Force degradation studies are performed at pre-clinical phase or phase I of clinical trial so that sufficient time provides to identifying structure elucidation, degradation products. If forced degradation studies are performed properly, manufacturing process of the new product can be developed properly and stability-indicating analytical procedures can be select more effectively.

What is the regulatory obligation regarding Force Degradation Studies?

Following ICH [International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use] Guidelines has been depicted regarding forced degradation studies but it covers only marketing applications for new products but not for during clinical development.

[][]ICH Q1A: Stability Testing of New Drug Substances and Products.
[][]ICH Q1B: Photo stability Testing of New Drug Substances and Products.
[][]ICH Q2B: Validation of Analytical Procedures: Methodology.

What actually says this guideline?

[][]ICH Q1A (Stress testing): Stability Testing of New Drug Substances and Products.

It implies for the performing of forced degradation studies for drug substances and drug products. The recommended condition is that the result shall be observe temperature above accelerated condition [Temperature>500C) and Humidity [75% relative humidity] including oxidation and photolysis. pH range may be wide for the testing of solution or suspension.

[][]ICH Q1B: Photo stability Testing of New Drug Substances and Products.

It implies the photo stability of drug substances and drug products. Section II and Section III describe the forced degradation conditions condition for drug substance and drug product. Exposure levels are not defined in Forced degradation studies. Photo stability testing can be performed both in Solid or in solution/suspension. Stability indicating method is developed based on this sample result. Some non-experiential degradation products may be formed during stability studies which may not be taken under consideration.

[][]ICH Q2B: Validation of Analytical Procedures: Methodology.

Provide guideline regarding analytical meth validation. Gives guidance to validate the analytical methodology. To demonstrate specificity, in section B1.2.2 (impurities not available) there is a recommendation to utilize samples from the forced degradation studies.

Verdict

to develop degradation pathways, Forced degradation studies are the prominent way & Forced degradation studies are the prominent way to develop degradation pathways and to detect degradation products of API [Active pharmaceutical Ingredients], further it simplifies elucidation of degradants structure. Forced degradation studies also simplify the chemical & physical stability analysis of drug substances & drug products. To develop manufacturing conditions, storage conditions & determine expiry date of a new drug formulation Forced degradation studies is considered as key studies.

Forced Degradation Study or Stress Testing Procedure Read More »

Comparative Dissolution Study procedure

Comparative Dissolution, General Overview

[][]Comparative Dissolution, Oral dosage form like Table & Capsule are more popular than IV/IM(Intravenous/Intramuscular) Injection formulation. From the very beginning, people are most familiar with oral solid dosage form (Tablet, Capsule, Powder etc.) and becoming more popular till today as no special technique or device is not require to administer these products and associated pain is not involved here.

[][]In the period of time its are considered as the most effective and efficient method to treat the patient. This orally taken drugs are dissolved in GI (Gastro Intestinal) fluid and then bioavailable at the systemic circulation as it absorbed here. To measure the bioavailability of a certain drugs (in vivo Analysis, vivo is Latin for “within the living, test perform in living organism) is not accurately possible due to its complex nature.

[][]For this reason, in vitro (vitro is Latin for “within the glass, test perform outside the living organism) methods are followed to measure the dissolution rate of a certain drugs. This method is officially recognized by certain regulatory authority and it(in vitro study) considered most convenient way to develop new formulation of oral solid dosage form.

Comparative Dissolution Consideration

[][]Dissolution method is the best option for the lower strength drug where different strength is proportionally formulated to acquire the biowaiver of certain formulated drug. For a certain product which higher strength bioequivalence study has been carried out and found proportional to the concentration then biowaiver is conceivable to the lower strength.

Dissolution test are considering the most quality control tool for the commercial batch to batch product to monitor its consistency over a certain period of time. It also provides significant information during post approval changes of the certain product as changes made in formulation, manufacturing process and different scale up procedure.

[][]The most physiological factor is considered as the dissolution and solubility of the API and its permeability through the membrane of the GI[Gastro Intestinal] tract. As this measurement is so prone to error due to its complex nature then in vitro study consider the most convenient and reliable procedure to achieve the required target. During development of a certain solid dosage form, dissolution is considered as the best option to determine its quality parameter which have the great impact on the bioavailability of the formulated product.

Comparative Dissolution, Waiver of in vivo bioavailability

[][]BCS system applied in this case so that waiver for in vivo analysis can be assured. BCS [Biopharmaceutical Classification System] is a system which measure the permeability and solubility of drugs in a certain prescribed condition.

[][]The actual aim of BCS is to aid the post approval changes and arranging approval activities based on in vitro data studies.

This system has been optimized based on the oral solid dosage unit as most of the market products are available at oral dosage form [More than 50% total market share, US$23.4 Bn in 2021, US$24.7 Bn in 2022 as estimated, growth rate 5.9%).

[][]Waivers[ means giving permission to skip in vivo bioequivalence study] is actually reserved for those products that meet the specific requirements of solubility & permeability & most of the cases rapid dissolve in body fluid.

[][]Using the BCS, appropriate formulation study shall be developed such as Type II drugs designed as Permeable but insoluble, this class is not the actual right candidate for development of a new moiety.

[][]So, solubility shall be developed to acquire the right dissolution profile. Based on the solubility and permeability BCS has classified the four categories of the product as depicted below

Dosage form challenge

[][]Comparison has been drawn from old drug to new drug formulation, where older drugs compare to the current products are more prone to solubilities. Class II compound has been remarkably increased as 30% to 60% where class I compound has down to 40% to 20% where low solubility has the main cause to encounter the issue.

 A oral solid dosage form is the preferred option but all time this can’t possible the suspension or solution is continued to prove its existence  

[][]Generally a highly soluble active substance and rapidly dissolve dosage form provide better bioavailability and in this case biowaiver can be waived for bioequivalence studies base on its dissolution profile.

[][]If a active substance found low solubility but high permeability then the rate limiting steps of absorption may be consider as dissolution. Most of the cases dissolution profile control the more than one of excipients or special design matrix compounds. So Test condition may be consider as various time frame (10, 15, 20,30, 45 & 6 minutes).

[][]Drugs that are poor soluble in water then various time frame are considered and accepted timeframe is set for dissolution profile. Here USP Type 4 apparatus to be used to develop such type dissolution profile. Most of the time, monograph for combination product is not available at BP or USP the individual monograph shall be used to set the dissolution profile.

Selection of Dissolution Media

Selection of the dissolution media is the vital point to achieve the goal. pH of the media as the key role as all of the dosage form goes to GI[Gastro Intestinal] tract so pH shall be simulate with the GI Tract environment. pH shall be 1.2 to 6.8 which is the physiologic pH range of the body.

ZonepH
[A]Pre-prandial
Stomach
1.8(1~3)
Duodenum6.0(4~7)
Upper Jejunum 6.5(5.5~7)
Lower Jejunum 6.8(6~7.2)
Upper Ileum7.2(6.5~7.5)
Lower Ileum7.5(7~8)
Proximal Colon(5.5 ~6.5)
[B]Post-prandial
Stomach
4.0(3~6)
Duodenum5.0(4~7)
Upper Jejunum 5.5(5.5~7)
Lower Jejunum 6.5(6~7.2)
Upper Ileum7.2(6.5~7.5)
Lower Ileum7.5(7~8)
Proximal Colon(5.5 ~6.5)

Dissolution Statistics

Different cases obtaining after multipoint dissolution which is calculative as follows:
[][]If Test Product and Reference Product both shows dissolution rate more than 85% within first 15 minutes then no calculation is required, they are considered as similar. If it didn’t achieved then seek for next step.
[][]Seek for f2 value[ f2, similarity factor] if f2>50% then it consider similar then in vivo study is not required.
[][]Difference Factor [f1] is the percentage (%) difference between the two curve at the each time period and also measure the relative error between two curve.

How it works

To determine the difference and similarity factor(f2) following pont shall be noted:
[][]Use the Two different products for study, from each product collect 12 unit [12 unit from Test Product & 12 Unit from Reference Product].

[][]Three time point shall be considered[Exclude Point Zero], only one measurement after 85% shall be measured.
[][]Produced curve shall be similar, f2 values shall be close to 100. Most of the time f2 value more than 50 denote similarity of the two curves as well as equivalence of the two products.

 If Three/Four Time points come to the test then following points shall be considered. 

[][]The measurement for the Test Product and the Reference product shall be same. Dissolution Time point shall be same for the both product (10,15,20,30,45,60 minutes etc.). Products which tend to faster dissolution (85% dissolve within 30 minutes) then time frame shall be consider as 10, 15, 20, 30 minutes.
[][]Only One measurement shall be consider after completion of 85% dissolution of both sample and reference products.

System Requirements to Perform Comparative Dissolution

Dissolution Activities shall be continued on USP Type I Dissolution apparatus at 100 RPM or USP Type II Apparatus at 50 RPM using 900 ml of different dissolution media mentioned below.
[][]Media Use in Comparative Dissolution
[][]Acid Media: 0.1N HCL or Simulated Gastric Fluid USP without Enzyme
[][]Acetate Buffer pH 4.5
[][]Phosphate Buffer pH 6.8 or Simulated Intestinal Fluid without Enzyme
[][]If both the Test Product and Reference product shows more than 85% dissolution within first 15 minutes then no calculation required. If not meets the above requirements then calculate f2 Value.
[][]If found f2>50, then the profile considered as similar and in vivo study is not required. Minimum 12 unit of each shall be consider for comparative dissolution.

Comparative Dissolution Study procedure Read More »

Performance Qualification of WFI Phase 3

Performance Qualification of WFI,  Purpose

Performance Qualification of WFI, To authenticate and document that the performance of the WFI Generation and Distribution System installed at the WFI & PS plant room (roof top) of Cephalosporin Block of XX Pharmaceuticals Limited is satisfactory in all critical features related to the operational requirements during Phase – 3 study.

Performance Qualification of WFI, Scope

This protocol will be applicable for performing Phase – 3 validation study to verify that the Water For Injection generation and distribution system installed at WFI & PS plant room (roof top) of Cephalosporin Block of XX Pharmaceuticals Limited consistently produce desired quality of Water For Injection over the study period of 01 year.

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Water For Injection Performance Qualification of Phase 2 Study

Responsibilities

[][]Preparation of the protocol
Validation (Engineering) Department.
[][]Executing the protocol
Validation team along with respective departmental person and engineers or other suitably qualified staff allocated from the site or contracted specialists as appropriate.
[][]Chemical test
Quality Control Department
[][]Microbiological Test
Microbiology Department
[][]Data documentation and preparation of the report
Validation (Engineering) department.
[][]Verifying the report
Concerned departmental person.
[][]Providing documentation on the equipment
Related departments i.e. Engineering, Quality Control, Microbiology, Validation.

System And Process Description

System Information

=>Manufacturer : Watertown
=>Capacity : 750 ltr/hr
=>Model : MS750/4T
=>Manufacturer no. : MS1132

The System under test

[][]The Water For Injection system is designed to generate and distribute the desired quantity & quality of Water For Injection to various user points.

Generation system of Water For Injection

[][]The WFI production process consists of purified water evaporation followed by pure steam separation and condensation through four multi-effect water still columns.

[][]Purified water from the storage tank is pressurized through a feed water pump and pre heated in the four pre heaters.

[][]Then, the purified water becomes pure steam in the four multi effect columns by exchanging heat with the plant steam.

[][]There are two condensers in the system. The first condenser is used to cool the pure steam by exchanging heat with the incoming feed water (PW).

[][]Finally, the WFI is produced in second condenser by exchanging heat with the chilled water which is then supplied to the WFI storage tank.

Distribution system of Water For Injection

[][]The WFI is stored in a WFI storage tank of 2000 ltr capacity and is distributed to the user points and circulated within a loop by a high pressure pump.

[][]There is a heat exchanger in the distribution section to sterilize the whole distribution system.

Tests To Be Performed And Sampling Plan

[][]A comprehensive validation study plan has been established where a weekly sampling plan has been developed for Phase-3 study of WFI system for 01 year concerning weekly testing of all main sampling points.

[][]The sampling will be taken one day a week on working days. The acceptance criterion of the tests are stated in the table.

Main Sampling Points

The sampling points of WFI are listed below:

Sl. No.Sample IDUser point LocationTestsMicrobial Count/
Chemical Tests
01WSP-1Final WFI after condenser – 2 (before WFI storage tank).Next TableWeekly
02WSP-2At supply of WFI Distribution LoopNext TableWeekly
03WSP-3At return of WFI Distribution LoopNext TableWeekly
04WUSP – 01WFI Distribution LoopNext TableWeekly
05WUSP – 02WFI Distribution LoopNext TableWeekly
06WUSP – 03WFI Distribution LoopNext TableWeekly
07WUSP – 04Cold User pointNext TableWeekly
Tests and Acceptance Criteria for Water for Injection

Sl. No.TestsFrequencyAcceptance CriteriaAlert LimitAction Limit
01Appearance Daily from each sampling point.Clear, colorless and odorless liquid.N/AN/A
02Conductivity Daily from each sampling point.Not more than 1.1 µS/cm at 20⁰C or
Not more than 1.3 µS/cm at 25⁰C
0.7 µS/cm0.9 µS/cm
03Total Organic CarbonDaily from each sampling point.Not more than 500 ppb106.4 ppb135.8 ppb
04Total Viable Microbial CountDaily from each sampling point.Not more than 10 CFU/100 mL5 CFU/100 mL8 CFU/100 mL
05E.coliDaily from each sampling point.Must be AbsentN/AN/A
06Staphylococcus aureusDaily from each sampling point.Must be AbsentN/AN/A
07Pseudomonas aeruginosaDaily from each sampling point.Must be AbsentN/AN/A
08Salmonella sppDaily from each sampling point.Must be AbsentN/AN/A
09Bacterial EndotoxinsDaily from each sampling point.Less than 0.25 EU /mLN/AN/A

[][]Performance Qualification shall be considered acceptable when all the conditions above have been met.
[][]Any deviation from the acceptance criteria of the specific check point shall be reported and decision should be taken for the rejection, replacement or rectification of the equipment/component/system.

Conclusion

[][]The results of the Phase – 3 study, as per the qualification protocol are recorded & analyzed.

[][]The observed parameters/tests and subsequent analytical results show that the Water For Injection Generation and Distribution System Complies/Does Not Comply as per the predetermined acceptance criteria.
[][]Hence, the Water For Injection Generation and Distribution is / is not qualifying the Phase – 3 study of Performance Qualification and the System can be / cannot be used for production purpose and continued to regular monitoring by Quality Control and Microbiology department.

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Performance Qualification Protocol of WFI Phase 3

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Water For Injection Performance Qualification in Phase 2 Study

Water For Injection Performance Qualification, Purpose

Water For Injection Performance Qualification, To validate and archive that the exhibition of the WFI Generation and Distribution System introduced at the WFI and PS plant room (rooftop top) of Cephalosporin Block of XX Pharmaceuticals Limited (XPL) is agreeable in all basic elements connected with the functional necessities during Phase – 2 Study.

Water For Injection Performance Qualification, Scope

This Protocol will be relevant for performing Phase – 2 study to check that the Water For Injection generation and conveyance framework introduced at WFI and PS plant room (rooftop top) of Cephalosporin Block of XX Pharmaceuticals Limited, reliably produce wanted nature of Water For Injection over the review time of 20 continuous working days.

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Water For Injection Performance Qualification Phase I Study

Responsibilities

[][]Preparation of the protocol
Validation (Engineering) Department.
[][]Executing the protocol
Validation team along with respective departmental person and engineers or other suitably qualified staff allocated from the site or contracted specialists as appropriate.
[][]Chemical test
Quality Control Department
[][]Microbiological Test
Microbiology Department
[][]Data documentation and preparation of the report
Validation (Engineering) department.
[][]Verifying the report
Concerned departmental person.
[][]Providing documentation on the equipment
Related departments i.e. Engineering, Quality Control, Microbiology, Validation.

System & Processing

System Information
Manufacturer : Watertown
Capacity : 750 ltr/hr
Model : MS750/4T
Manufacturer no. : MS1132

The System under test

The Water For Injection system is designed to generate and distribute the desired quantity & quality of Water For Injection to various user points.

Generation system of Water For Injection

[][]The WFI manufacturing process consists of purified water evaporation followed by pure steam separation & condensation through four multi-effect water still columns.

[][]Purified water from the storage tank is pressurized through feed water pump & pre heated in the four pre-heaters.

[][]Then, the purified water becomes pure steam in the four multi effect columns by exchanging heat with the plant steam.

[][]There are two condensers in the system. The first condenser is used to cool the pure steam by exchanging heat with the incoming feed water (PW).

[][]Finally, the WFI is produced in second condenser by exchanging heat with the chilled water which is then supplied to the WFI storage tank.

Distribution system of Water For Injection

The WFI is stored in a WFI storage tank of 2000 L capacity and is distributed to the user points and circulated within a loop by a high pressure pump. There is a heat exchanger in the distribution section to sterilize the whole distribution system.

Test to be perform & Sampling

[][]A comprehensive validation study plan has been established where a daily sampling plan has been developed for Phase-2 study of WFI system for 20 consecutive working days concerning daily testing of all main sampling points.The acceptance criterion of the tests are stated in the table of section.

Main Sampling Points

The sampling points of WFI are listed below:

Sl. No.Sample IDRoom NameTestsMicrobial Count/
Chemical Tests
01WSP-1WFI and Pure Steam plant roomBelow TableDaily
02WSP-2WFI and Pure Steam plant roomBelow TableDaily
03WSP-3WFI and Pure Steam plant roomBelow TableDaily
04WUSP – 01Vial Washing & SterilizationBelow TableDaily
05WUSP – 02Laundry & WashBelow TableDaily
06WUSP – 03Wash BayBelow TableDaily
07WUSP – 04Laundry & WashBelow TableDaily

[][]Performance Qualification shall be considered acceptable when all the conditions above have been met.
[][]Any deviation from the acceptance criteria of the specific check point shall be reported and decision should be taken for the rejection, replacement or rectification of the equipment/component/system.

Tests and Acceptance Criteria for Water for Injection (Based on Current USP 37)

Sl. No.TestsFrequencyAcceptance CriteriaAlert Limit
01Appearance Daily from each sampling point.Clear, colorless and odorless liquid.Not Available
02Conductivity Daily from each sampling point.Not more than 1.1 µS/cm at 20⁰C or
Not more than 1.3 µS/cm at 25⁰C
Not Available
03Total Organic CarbonDaily from each sampling point.Not more than 500 ppbNot Available
04Total Viable Microbial CountDaily from each sampling point.Not more than 10 CFU/100 mLNot Available
05E.coliDaily from each sampling point.Must be AbsentNot Available
06Staphylococcus aureusDaily from each sampling point.Must be AbsentNot Available
07Pseudomonas aeruginosaDaily from each sampling point.Must be AbsentNot Available
08Salmonella sppDaily from each sampling point.Must be AbsentNot Available
09Bacterial EndotoxinsDaily from each sampling point.Less than 0.25 EU /mLNot Available
Reference Documents

Sl. No.Title of the DocumentDocument No.
01WHO Good Manufacturing Practices: water for pharmaceutical use.WHO Technical Report Series, No. 929, 2005
02WHO Expert Committee on Specifications for Pharmaceutical Preparations.WHO Technical Report Series No. 970, 2012
03United States Pharmacopeia 37Not Available

Conclusion

[][]The results of the Phase – 2 study, as per the qualification protocol are recorded & analyzed. The observed parameters/tests and subsequent analytical results show that the Water For Injection Generation and Distribution System Complies/Does Not Comply as per the predetermined acceptance criteria.

[][]Hence, the Water For Injection Generation and Distribution is / is not qualifying the Phase – 2 study of Performance Qualification and the System can be / cannot be used for production purpose and continued to Phase – 3 study.

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Water For Injection Performance Qualification Phase 2 Study

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WFI Performance Qualification, Phase-I Study

WFI Performance Qualification, Purpose

WFI Performance Qualification, To authenticate and document that the performance of the WFI Generation and Distribution System installed at the WFI & PS plant room of Cephalosporin Block of XX Pharmaceuticals Limited (XPL) is satisfactory in all critical features related to the operational requirements during Phase – 1 (Investigational Phase) study.

WFI Performance Qualification, Scope

This protocol will be applicable for performing Phase -1 validation study to verify that the Water For Injection generation and distribution system installed at the utility area (roof top) of Cephalosporin Block of XX Pharmaceuticals Limited,  consistently produce desired quality of Water For Injection over the study period of 20 consecutive working days.

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Pure Steam System Performance Qualification

Responsibilities

[][]Preparation of the protocol
=>Validation (Engineering) Department.
[][]Executing the protocol
=>Validation team along with respective departmental person and engineers or other suitably qualified staff allocated from the site or contracted specialists as appropriate.
[][]Chemical Test
=>Quality Control Department
[][]Microbiological Test
=>Microbiology Department
[][]Data documentation and preparation of the report
=>Validation (Engineering) department.
[][]Verifying of the report
=>Concerned departmental person.
[][]Providing documentation on the equipment
=>Related departments i.e. Engineering, Quality Control, Microbiology, Validation.

System And Process Description

=>System Information

=>Manufacturer : Watertown
=>Capacity : 750 ltr/hr
=>Model : MS750/4T
=>Manufacturer no. : MS1132

The System under test

The Water For Injection system is designed to generate and distribute the desired quantity & quality of Water For Injection to various user points.

Generation system of Water For Injection

[][]The WFI production process consists of purified water evaporation followed by pure steam separation and condensation through four multi-effect water still columns.

[][]Purified water from the storage tank is pressurized through a feed water pump and pre heated in the four pre heaters.

[][]Then, the purified water becomes pure steam in the four multi effect columns by exchanging heat with the plant steam.

[][]There are two condensers in the system. The first condenser is used to cool the pure steam by exchanging heat with the incoming feed water (PW).

[][]Finally, the WFI is produced in second condenser by exchanging heat with the chilled water which is then supplied to the WFI storage tank.

Distribution system of Water For Injection

[][]The WFI is stored in a WFI storage tank of 2000 ltr capacity and is distributed to the user points and circulated within a loop by a high pressure pump.

[][]There is a heat exchanger in the distribution section to sterilize the whole distribution system.

Tests To Be Performed And Sampling Plan

[][]A complete validation study plan has been designed in accordance with the Validation Master Plan. In addition, a daily sampling plan has been also developed for Phase-1 study of WFI system for 20 consecutive working days concerning daily testing of all main sampling points .

[][]The acceptance criterion of each test is stated in the next table.
[][]Alert and action limits will be calculated using following formula after getting the test results and data:
=>Alert limit = Average value + 2σ
=>Action limit = Average value + 3σ

Main Sampling Points

The sampling points of WFI are listed below:

Sl. No.Sample IDRoom NumberUser point LocationTestsMicrobial Count & Chemical Tests
01WSP-1SRT001Final WFI after condenser – 2 (before WFI storage tank).Mention on next TableDaily
02WSP-2SRT001At supply of WFI Distribution LoopMention on next TableDaily
03WSP-3SRT001At return of WFI Distribution LoopMention on next TableDaily
04WUSP – 01SPR054WFI Distribution LoopMention on next TableDaily
05WUSP – 02SPR040WFI Distribution LoopMention on next TableDaily
06WUSP – 03SMB010WFI Distribution LoopMention on next TableDaily
07WUSP – 04SPR040Cold User pointMention on next TableDaily

[][]Performance Qualification shall be considered acceptable when all the conditions above have been met.
[][]Any deviation from the acceptance criteria of the specific check point shall be reported and decision should be taken for the rejection, replacement or rectification of the equipment/component/system.

Tests And Acceptance Criteria For Water For Injection

Sl. No.TestsFrequencyAcceptance CriteriaAlert Limit
1Appearance DailyClear, colorless and odorless liquid.N/A
2Conductivity DailyNot more than 1.1 µS/cm at 20⁰C or
Not more than 1.3 µS/cm at 25⁰C
N/A
3Total Organic CarbonDailyNot more than 500 ppbN/A
4Total Viable Microbial CountDailyNot more than 10 CFU/100 mLN/A
5E.coliDailyMust be AbsentN/A
6Staphylococcus aureusDailyMust be AbsentN/A
7Pseudomonas aeruginosaDailyMust be AbsentN/A
8Salmonella sppDailyMust be AbsentN/A
9Bacterial EndotoxinsDailyLess than 0.25 EU /mLN/A
Test Records

All the test reports of chemical and microbiological tests are attached with the report as attachment.

Reference Documents

Sl. No.Title of the DocumentDocument No.
01WHO Good Manufacturing Practices: water for pharmaceutical use.WHO Technical Report Series, No. 929, 2005
02WHO Expert Committee on Specifications for Pharmaceutical Preparations.WHO Technical Report Series No. 970, 2012
03United States Pharmacopeia N/A

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WFI Performance Qualification, Phase-I Study Protocol

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Vial Washing Machine Performance Qualification

Vial Washing Machine Performance Qualification, Purpose

Vial Washing Machine Performance Qualification, To authenticate and document that the performance of the Vial Washing Machine of Sterile Production area (Cephalosporin Block) of XX Pharmaceutical Limited (XPL) is satisfactory in all critical aspects related to the operational requirements during washing of vials. This protocol describes the performance qualification procedures of the Vial Washing Machine manufactured by Tofflon, China.

Vial Washing Machine Performance Qualification, Scope

This Performance Qualification (PQ) is to be performed against agreed acceptance criteria on 7.5 ml, 15 ml and 30 ml vials which will be washed by the Vial Washing Machine installed in the Sterile Production area of Cephalosporin Block of XX Pharmaceutical Limited.

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Responsibilities

[][]Preparation of the protocol

Validation (Engineering) Department with the assistance of Microbiology, Engineering and Maintenance department.
Executing the protocol

[][]Validation (Engineering) Department along with respective departmental person and engineers or other suitably qualified staff allocated from the site or contracted specialists as appropriate.
[][]Microbiological Challenge Test

Microbiology department
[][]Chemical Tests

Quality Control Department
[][]Data documentation and preparation of the report

Validation (Engineering) department.
[][]Verifying of the report

Concerned departmental person.
[][]Providing documentation on the equipment

Related departments i.e. Engineering, Production, Microbiology, Validation or other appropriate departments and manufacturer.

System And Process Description

[][]Equipment Information
=>Manufacturer : Tofflon, China
=>Capacity : 6000 – 9000 vials/hr.
=>Model : QCLX60
=>Serial no. : YF2014-078A

[][]The Equipment under test
The vials from the box are placed on the infeed conveyor belt and are showered by recycled WFI at first. Then, these are cleaned in the ultrasonic bath and transferred to the grippers. The infeed rotary screw transports the vials from the housing to the grippers. There are total twenty stations where 60 vials are washed using following sequence:
=>Internal blowing with compressed air.
=>Internal and external spraying with recycled WFI at ambient temperature.
=>Internal blowing with sterile compressed air.
=>Internal and external spraying with fresh WFI.
=>Internal blowing with compressed air.
=>Internal and external blowing with sterile compressed air.
=>The supply lines are equipped by filter with the following retention grade: compressed air 0.22 µm, recycled WFI 10 µm and 5 µm, and fresh WFI 0.22 µm.

Checking Parameters

The PQ of Vial Washing Machine will be carried out to evaluate the following conditions to confirm the sterilization conditions:
i) Riboflavin Test.
ii) Particulate Matter Test.
iii) Bacterial Endotoxin Test.
iv) Washing Efficiency Test.

Study Procedure:

[][]Riboflavin Test: Take the Vials and do the decartoning and check for any Physical deformity or damage. A 0.2 gm riboflavin sodium phosphate per liter of purified water solution is prepared.

[][]Take 60 vials, mark with the permanent marker and spray the interior and exterior of the vials with the solution so that every vial is properly moistened with the solution and keep for overnight.

[][]Next morning dry the vials in oven for 2 hrs at 150 °C. After that, rinse the vials with phosphate buffer solution of pH 7.0 and measure the absorption in a UV-VIS spectrophotometer using 1 cm cell at a wavelength 266 nm by setting the limit between 230 nm and 350 nm.

[][]Use phosphate buffer solution of pH 7.0 as blank. Record the spectrum. Place the marked 60 Vials with these and run the machine as per SOP and collect these vials after washing.

[][]Take these vials again; repeat the procedure in order to confirm the presence of any riboflavin on vials.
The test will be repeated at minimum and maximum speed of washing machine for each of three vials’ sizes 7.5ml, 15ml and 30ml.

[][]The results of above test will be attached with the report and will be accepted if met the acceptance criteria.

Acceptance Criteria:

Riboflavin content must be absent in all the spiked vials after washing.

Particulate Matter Test:

[][]10 gm of charcoal is dissolved in 1000 gm WFI to make 1% charcoal slurry.

[][]Approximately 0.1 ml of charcoal slurry is used to spike each of 60 vials by swirling the vial to coat the inner surface and evaporate the solution to dryness at room temperature.

[][]Spiked test vials with charcoal are marked in series with permanent marker on the outer surface.

[][]Take the particle count of the vials before washing. After that, load these vials on the tray and run the machine according to the SOP No.____________________.

[][]The test must be performed at minimum and maximum speed of washing machine for each of three vials’ sizes 7.5ml, 15ml and 30ml.
[][]The results of above test will be attached with the report and will be accepted if met the acceptance criteria.

Acceptance Criteria:

Vials should be free from foreign particle & fibers on visual inspection. 10µ particles should not be more than 25 and 25µ particles should not be more than 3.

Bacterial Endotoxin Test:

[][]Add 100 endotoxin units into 10 vials and allow them to dry at 45 – 50°C. Mark these spiked vials with permanent marker on outer surface.

[][]Separate 10 vials are used for each of above tests. About 3000 vials of selected size are loaded on the feed belt and vial washing machine is operated as per the standard operating procedure.

[][]Place the spiked vials marked with permanent marker in between the other vials while machine is running. Collect the marked vials after washing and store properly to avoid the other contamination from environment.

[][]These spiked vials are analyzed separately. It should be done three times for each vial size. The test must be performed at minimum and maximum speed of washing machine for each of three vials’ sizes 7.5ml, 15ml and 30ml.
[][]The results of above test will be attached with the report and will be accepted if met the acceptance criteria.

Acceptance Criteria:

Vials should comply endotoxin limit within 0.25 EU/vial.

[][]Following parameter also maintained as per protocol

=>Deviation And Failure Investigation Summary

=>Documentation Requirements

=>Report Summary

Conclusion

The performance qualification Complies / Does Not Comply with the acceptance criteria taken above and the results obtained are attached with the protocol.
The Vial Washing Machine of Sterile Production area of Cephalosporin Block is / is not qualifying the Performance Qualification test as per this Protocol. Therefore, the Vial Washing Machine can be / cannot be used for production operation.

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Vial washing Machine Performance Qualification Protocol

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Laminar Air Flow Performance Qualification

Laminar Air Flow Performance Qualification, Purpose

Laminar Air Flow Performance Qualification, To authenticate and document that the performance of the Laminar Air Flow unit of Sterile Production area of Cephalosporin Block of XX Pharmaceuticals Limited (XPL) meets the user’s requirements of XPL Pharmaceutical Limited.

Laminar Air Flow Performance Qualification, Scope

This Performance Qualification (PQ) is to be performed against agreed acceptance criteria on the Laminar Air Flow Unit, which has been installed above the turn table after Depyrogenation Tunnel in Room of Sterile Production floor of Cephalosporin Block.

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Responsibilities

  • Preparation of the protocol
    -Engineering Department with the assistance of Validation team.
  • Executing the protocol
    -Validation (Engineering) Department along with respective departmental person and engineers or other suitably qualified staff allocated from the site or contracted specialists as appropriate.
  • Microbiological Test
    -Microbiology department
  • Data documentation and preparation of the report
    -Validation (Engineering) department.
  • Verifying of the report
    -Concerned departmental person.
  • Providing documentation on the equipment
    -Related departments i.e. Engineering, Production, Microbiology, Validation or other appropriate departments and manufacturer.

Performance testing

  • Air borne particle count test
    =>Purpose: the purpose of this test is to ensure that the air borne particles are under the acceptance limit.
    =>Test method: carry out the particle count test according to respective sop. Perform the test at rest and in operation conditions for 3 consecutive working days at each condition. Record the results in appendix – 1.
    =>Test instrument id:
    =>Acceptance criteria: the particle count specifications under the laminar air flow unit should meet the specification of room class a.

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Microbial Count test

  • Purpose: To ensure that the microbial count meets the specification of clean room class A.
  • Test Method: Perform the test at rest and in operation conditions for 3 consecutive working days at each condition. All results must be recorded on the appropriate forms of monitoring methodology and be compared with the alarm and specified action limits. The limits of sterile and non-sterile applications are specified below. Details are to be recorded in Appendix – 2.
  • Test Instrument ID: N/A
  • Acceptance Criteria: The microbial count must meet the clean room class – A specifications.

Sl. No.Room ClassAir Sample
(cfu/m3)
Settle Plates
(cfu/4 hours)
Contact Plate (cfu/plate)
01A<1<1<1
02B1055

Deviation And Failure Investigation Summary

Record in the column below any deviations or failures that occurred during the PQ exercise.

Deviation/ FailureDeviation/ FailureDescription and assessment of impact on validationInitialDate
1
2
3

Reference Documents

Sl. No.Title of the DocumentDocument No.
01Clean rooms and associated controlled environments part 1: classification of air cleanlinessISO 14644 – 1
02Clean rooms and associated controlled environments Part 3: Test methodsISO 14644 – 2
03Standard Operating Procedure For
Environmental Monitoring (Microbial & Particle Count)
In-house SOP

Conclusion

  • The performance qualification complies / does not comply with the acceptance criteria taken above and the obtained results are attached with the protocol.
  • The laminar air flow unit of sterile production area of cephalosporin block is / is not qualifying the performance qualification test as per this protocol.
  • Hence, the system can be / cannot be used for normal operation.

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Laminar Air Flow Performance Qualification Protocol

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Laminar Air Flow Operational Qualification

Laminar Air Flow Operational Qualification, Purpose

Laminar Air Flow Operational Qualification, To authenticate and document that the Laminar Air Flow Unit of Sterile production area of Cephalosporin Block of XX Pharmaceuticals Limited (XPL) operates as designed and intended. The operational parameters should be consistent with the requirements for the manufacturing process.

Laminar Air Flow Operational Qualification, Scope

This Operational Qualification (OQ) is to be performed against agreed acceptance criteria on the Laminar Air Flow Unit installed above the turn table after Depyrogenation Tunnel in Room of Sterile Production floor of Cephalosporin Block. The scope will include the verification of previously calibrated instruments and the availability of operational, maintenance and cleaning procedures.

Responsibility

  • Preparation of protocol
    -Engineering Department.
  • Executing the protocol
    -Engineering department or other suitably qualified staff allocated from the site or contracted specialists as appropriate.
  • Providing documentation of the equipment
    -Related departments i.e. Engineering Production, Validation or other appropriate departments and manufacturer.
  • Data documentation and preparation of the report
    -Raw data documentation is the responsibility of those conducting the validation. Preparation of the report and incorporation of data will be the responsibility of the Engineering Department.

Background

Project Description & Related issues
[][]This Laminar Air Flow Unit has been installed in the year 20xx in the sterile production area of Cephalosporin Block for dispensing of raw materials.

Purchasing Information

[][]Manufacturer: GUSU
[][]Local Agent: LS Techno Trade
[][]Model Number: GMP Standard

System Description

[][]A Laminar Air Flow Unit is used to provide unidirectional air flow. Grade A is ensured under LAF using H14 HEPA filter.

[][]A blower is used to circulate the air. The air flow direction of this LAF is vertical.

[][]There is a differential pressure gauge to see the differential pressure across the filters which indicate the blockage of filters.

Verification of Sops

[][]The standard operating procedure for operation and cleaning procedure of Laminar Air Flow Unit must be at least in draft format before commencement of OQ. The necessary information are recorded in the following table:

Sl. No.SOP NameEffective DateAcceptable
(Yes/ No)
Initials with date
01Operation and Cleaning of Laminar Air Flow Unit.
02

Verification of Training

  • Training should have been given regarding operation, maintenance and cleaning of Laminar Air Flow Unit to all operators and must be documented.
  • The documentation status is to be recorded in the following tables.
  • The training is to be recorded in the following tables.

Trainer NameTraining course/SOP NameTrainee NameInitialsDate

Operational testing

  • Verification of start-up and normal sequence of operation
  • Record results of checks in the following table:

Criterion No.Action to be takenAcceptance CriteriaCompliant
Yes/No
Initial/Date
01Switch ON the main power.The voltage will be shown on the display.
02Switch ON the blower by pressing the ON button.The blower has to be ON and air will start flowing vertically.
03Differential Pressure gauge for HEPA Filter is functioning properly.The differential pressure gauge should show pressure from zero to positive direction.

Smoke Test

  • Purpose: The purpose of the smoke test is to justify the airflow direction under the HEPA Filter is unidirectional.
  • Test Method:
  • The smoke test will be performed by ______________________ According to the SOP No. _____________________________.
    Test Equipment/Material: Dry Ice and water.
  • Acceptance Criteria: Airflow direction is unidirectional and vertical. Attach a copy of the report of Smoke test.

Filter Integrity Test

  • Purpose: Filter Integrity test is performed using Poly Alpha Olephin (PAO) to check any leakage of the filter.
  • Test Method: The test is performed by ____________________ according to the SOP NO. ______________________________.
  • Test Equipment: PAO generator, Optical Photometer.
  • Acceptance Criteria: Any leakage greater than 0.01% of the upstream challenge aerosol concentration is considered unacceptable and wants repairs and resetting.
  • Attach a copy of HEPA filter integrity test certificate in attachment.

Air Velocity Test

  • Purpose: The purpose of this test is to ensure the air velocity for laminar flow.

    Test Method:

  • Measure the air velocity under each HEPA filter of the equipment at the distance of 6” below the filter grill and record the velocity at 5 locations (Shown in following figure) and take the average reading with the anemometer.
  • Measure the air velocity under each HEPA filter of the equipment at the operation level and record the velocity at 5 locations (Shown in following figure) and take the average reading with the anemometer.
  • Test Equipment: Calibrated anemometer.
  • Acceptance Criteria: Measured air velocity should be in the range of 0.36 m/sec ~ 0.54 m/sec.
    Result:

No. 1 HEPA

No. 2 HEPA result shall be plotted.

Conclusion

[][]The Operational Qualification of Laminar Air Flow Unit of Cephalosporin Block Complies / Does Not Comply with the acceptance criteria taken above and the results obtained have been filled up in the respective table of each test.
[][]The Laminar Air Flow Unit of Cephalosporin Block is / is not qualifying the Operational Qualification test as per this Protocol. Hence, the system can be / cannot be used for Performance Qualification.

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Laminar Air Flow Operational Qualification

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Laminar Air Flow Installation Qualification

Laminar Air Flow Installation Qualification, Purpose

Laminar Air Flow Installation Qualification, To verify and document that the Laminar Air Flow Unit of Sterile Area of Cephalosporin Block is designed, built and installed according to XX Pharmaceuticals Limited’s demand and manufacturer specifications and that documentation is compiled to verify the integrity of the installation.

Laminar Air Flow Installation Qualification, Scope

This Installation Qualification (IQ) is to be performed against agreed acceptance criteria on the Laminar Air Flow Unit installed above the turn table after Depyrogenation Tunnel in Room of Sterile Production floor of Cephalosporin Block. The scope will include assessment of equipment design and installation, connection of utilities, presence and function of instruments.

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Responsibilities

[][]Preparation of protocol
=>Engineering Department.
[][]Executing the protocol
=>Engineering department or other suitably qualified staff allocated from the site or contracted specialists as appropriate.
[][]Providing documentation on the equipment
=>Related departments i.e. Engineering Production, Validation or other appropriate departments and manufacturer
[][]Data documentation and preparation of the report
=>Raw data documentation is the responsibility of those conducting the validation. Preparation of the report and incorporation of data will be the responsibility of the Engineering Department.

Background

[][]Project Description & Related issues
=>This Laminar Air Flow Unit has been installed in the year 20xx in the sterile production area of Cephalosporin Block for dispensing of raw materials.

Purchasing Information

Item/ Brand

=>Manufacturer: GUSU
=>Local Agent: Precisa Techno Trade
=>Model Number: Standard

System Description

A Laminar Air Flow Unit is used to provide unidirectional air flow. Grade A is ensured under LAF using H14 HEPA filter. A blower is used to circulate the air. The air flow direction of this LAF is vertical. There is a differential pressure gauge to see the differential pressure across the filters which indicate the blockage of filters.

Following Document Shall be noted:
[][]Verification of Installation
[][]Design Documentation
=>General Characteristics
=>Engineering Specifications
[][]Instruments verification
[][]Utility Verification
[][]Deviation and Failure Investigation Summary

Conclusion

[][]The Installation Qualification of Laminar Air Flow Unit of Cephalosporin Block Complies / Does Not Comply with the acceptance criteria taken above and the results obtained have been filled up in the respective table of each test.
[][]The Laminar Air Flow Unit of Cephalosporin Block is / is not qualifying the Installation Qualification test as per this Protocol. Hence, the system can be / cannot be used for Operational Qualification.

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Laminar Air Flow Installation Qualification

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Air Compressor Performance Qualification

Purpose

To determine that the oil free air compressor performs as per the given specifications, by running the system on its intended schedules and recording all relevant data under normal conditions & for worst-case situations where applicable.

Scope

This Performance Qualification (PQ) is to be performed against agreed acceptance criteria on the oil free air compressor systems, comprising of compressor, drying system, filtering system, piping, control system etc. installed in General Block of XX Pharmaceuticals Ltd. The scope will include measuring oil content, dew point test, particulate contamination and microbial count of compressed air system.

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Responsibilities

[][]Preparation of the protocol
=>Validation (Engineering) Department with the assistance of Microbiology, Quality Assurance and Engineering department.
[][]Executing the protocol
=>Validation team along with respective departmental person and engineers or other suitably qualified staffs allocated from the site or contracted specialists as appropriate.
[][]Oil and dew point test
=>Validation (Engineering) Department
[][]Microbiological Test
=>Microbiology Department
[][]Data documentation and preparation of the report
=>Validation (Engineering) department.
[][]Verifying of the report
=>Concerned departmental person.
[][]Providing documentation on the equipment
=>Related departments i.e. Engineering, Production, Microbiology, Validation or other appropriate departments and manufacturer.

System and process description

system information
=>Manufacturer : Atlas copco
=>Capacity : 10.4 m3/hr
=>Model : Zt-75
=>Serial no. : Apf166068

The System under test

[][]The Atlas Copco Air Compressor manufactured by Atlas Copco has a capacity of 10.4 m3/min. Air drawn through an air filter, is compressed in low-pressure compressor element and discharged to the intercooler.

[][]The cooled air is further compressed in high-pressure compressor element and discharged through silencer and after coolers. A check valve is provided downstream of the silencer.

[][]The compressed air leaves the compressor via the air outlet. The compressor delivers oil-free, pulsation-free air.
[][]This is an air cooled type compressor which is facilitated with air filter, moisture trap, high pressure and low pressure safety valve, desiccant type dryer system etc.
[][]After being compressed in compressor the oil free compressed air will be stored in a receiver tank. There are two desiccant type air dryers. Air is dried in the air dryers and then distributed through pipe line to the different facility.

Performance Tests

The tests for performance qualification of compressed air as follows:
#Oil content Test Method
[][]Ensure that the compressed air is supplied at a pressure between 2.8 – 3.2 bar.

[][]Connect the sampling point at the port of 10 bar of the pressure reducer of Drager Aerotest Simultan HP.

[][]After that, connect the measuring device with the pressure reducer and insert an oil impactor kit of Drager Aerotest Simultan HP into the oil testing port of the measuring device.

[][]Open the compressed air valve and collect the sample for 5 minutes. The time is counted by a calibrated timer.

[][]Finally, check the oil impactor kit if there is any spot on the screen. The following figures will be used to measure the quantity of the oil:

[][]Perform the test for 3 consecutive working days.
[][]Record the result in Appendix 1.

Acceptance Criteria

=>The compressed air should meet the specification of ISO 8573-1:2010 class 0. Hence, the compressed air must contain no oil.

Dew point test

Test Method
[][]Ensure that the compressed air is supplied at a pressure between 2.8 – 3.2 bar.

[][]Connect the sampling point at the port of 10 bar of the pressure reducer of Drager Aerotest Simultan HP.

[][]Break the both tips of a Water Content Test Kit. After that, connect the measuring device with the pressure reducer and insert a kit into the H2O testing port of the measuring device.

[][]Open the compressed air valve and collect the sample for 10 minutes.

[][]The time is counted by a calibrated timer. The color of the kit will be gradually changed from yellow to red.

[][]The reading is marked on the body of the kit. Get the reading up to which the color is changed.

[][]Calculate the dew point using the table provided in Appendix 06. Perform the test for 3 consecutive working days.
Record the result in Appendix 1.

#Acceptance Criteria
=>The compressed air should meet the specification of ISO 8573-1: 2010 class 2. Hence, the dew point of the compressed air must be equal to or less than – 400C.

Particulate contamination

Test Method

[][]Connect the sampling point with the High Pressure Diffuser and open the valve of compressed air to flush the line. After that, connect the other end of the High Pressure Diffuser with the air borne particle counter and commence particle counting for 0.5 micron and 5.0 micron particles.

[][]The sample collection time will depend on the room grade of the user point of compressed air.

[][]For example, if the user point is located in a Grade-D area, the sample will be collected for 1 minute. Please see the table of section for sample collection time for each grade.
[][]Perform the test for 3 consecutive working days.
[][]Record the results in the result sheet in Appendix 3.

#Acceptance Criteria

=>The specifications will differ according to the room classification, which are given below:

Maximum Permitted Number of Particles/m3

Room Class0.5mic.m5mic.m
A352020
B352029
C352000 2900
D352000029000

Microbial Count

Test Method

[][]The test will be performed according to the SOP No.: SOP/YY/XX where XX is the current revision of the SOP.
[][]Perform the test for 3 consecutive working days.
[][]Record the results in the result sheet in Appendix 4.

#Acceptance Criteria:

=>The specifications of this test according to the different room classifications are given below:

Room ClassAcceptance Limit
CFU/m3
Grade A<1
Grade B10
Grade C100
Grade D200

Sterility Test

Test Method
[][]This test will be performed only for ACSP – 03. The test will be performed according to the SOP No.: SOP, where XX is the current revision of the SOP.
[][]Perform the test for 3 consecutive working days. Record the results in the result sheet in Appendix 4.

#Acceptance Criteria:

=>The air at this point must be sterile.

Sampling Points and Test Frequency

[][]The list of sampling points which come into product contact is given below:

Sl. No.Sampling point nameRoom No.Room NameTestsFrequency
01Post StagingOil content, dew point, and particle count, microbial count 1 year
02Washing and Sterilization roomOil Content, Dew point and particle count, microbial count 1 year
03Vial Filling roomOil content, dew point, particle count and Sterility test1 year

Deviation And Failure Investigation Summary

=>In the column below, record any deviation or failure that occurred during the PQ exercise.

Reference Documents

=>ISO 8573-1:2010: Air Quality Classes.

Conclusion

[][]The Performance Qualification of Atlas Copco Air Compressor of General Block Complies / Does Not Comply with the acceptance criteria taken above and the results obtained are attached with the protocol.
[][]The Atlas Copco Air Compressor is / is not qualifying the Performance Qualification test as per this Protocol. Hence, the system can be / cannot be used for production operation.

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Air Compressor Performance Qualification Protocol

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Air Compressor Operational Qualification

Air Compressor Operational Qualification , Purpose

Air Compressor Operational Qualification , To verify and document that the oil free air compressor system operates as designed and intended. The operational parameters should be consistent with the requirements for the Manufacturing process. The OQ is aimed to verify that the installed equipment performs according to the manufacturer’s specifications.

Air Compressor Operational Qualification , Scope

This Operational Qualification (OQ) is to be performed against agreed acceptance criteria on the air compressor systems, comprising of compressor, drying system, filtering system, piping, control system etc. installed in the General Block of XX Pharmaceuticals Ltd. The scope will include assessment of equipment design and installation, connection to utilities, presence & function of instruments.
The scope will include the operational testing of the normal sequence of operation and verification of the target limits of operation.

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Responsibility

[][]Preparation of protocol
=>Engineering Department.
[][]Executing the protocol
=>Engineering department or other suitably qualified staff allocated from the site or contracted specialists as appropriate.
[][]Providing documentation on the equipment
=>Related departments i.e. engineering Production, Validation or other appropriate departments and manufacturer.
[][]Data documentation and preparation of the report
=>Raw data documentation is the responsibility of those conducting the validation. Preparation of the report and incorporation of data will be the responsibility of the Engineering Department.

Background

Project Description & Related issues
[][]This air compressor system is installed to serve General and Cephalosporin Block. To meet the demand of quality of compressed air, this oil free air compressor has been installed.

Purchasing Information

ItemBrandModelOrigin
Air CompressorAtlas CopcoZT 75Belgium
DryerAtlas CopcoCD185+Belgium
Air receiverAtlas CopcoNAGermany
Piping and distributionFabricated N/ALocal

System Description

[][]The Atlas Copco Air Compressor and Air Dryer manufactured by Atlas Copco has a capacity of 10.4 m3/min. Air drawn through an air filter is compressed in low-pressure compressor element and discharged to the intercooler.

[][]The cooled air is further compressed in high-pressure compressor element and discharged through silencer and after coolers.

[][]A check valve is provided downstream of the silencer. The compressed air leaves the compressor via the air outlet. The compressor delivers oil-free, pulsation-free air.
This is an air cooled type compressor which is facilitated with air filter, moisture trap, high pressure and low pressure safety valve, desiccant type dryer system etc.

Following parameter shall be perform at the time of Operational Qualification

[][]Verification of completion of sops
[][]Verification of training
[][]Operational testing
[][]Instrument calibration
[][]Deviation and failure investigation summary
[][]Report summary

Conclusion

The Operational Qualification of Compressed Air System installed at General Block Complies / Does Not Comply with the acceptance criteria taken above and the results obtained are attached with the protocol.
The Compressed Air System is / is not qualifying the Operational Qualification test as per this Protocol. Hence, the system can be / cannot be used for Performance Qualification.

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Air Compressor Operational Qualification Protocol

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Air Compressor Installation Qualification Protocol

Air Compressor Installation Qualification, Purpose

Air Compressor Installation Qualification, To verify and document that the oil free air compressor systems are designed, built and installed according to the XX Pharmaceuticals Ltd. demand and manufacturer specifications and documentation is compiled to verify the integrity of the installation.
This should result in acceptable documented evidence that the oil free air compressor system have been correctly installed in compliance with specification. This new IQ protocol will focus both the General and Cephalosporin Block.

Air Compressor Installation Qualification, Scope

This Installation Qualification (IQ) is to be performed against agreed acceptance criteria on the air compressor systems, comprising of compressor, drying system, filtering system, piping, control system etc. installed in the General Manufacturing area at the XX Pharmaceuticals Ltd. The scope will include assessment of equipment design and installation, connection to utilities, presence & function of instruments.

 

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Responsibilities

[][]Preparation of protocol
=>Engineering Department
[][]Executing the protocol
=>Engineering department or other suitably qualified staff allocated from the site or contracted specialists as appropriate.
[][]Providing documentation on the equipment
=>Related departments i.e. Engineering, Validation or other appropriate departments and manufacturer
[][]Data documentation and preparation of the report
=>Raw data documentation is the responsibility of those conducting the validation. Preparation of the report and incorporation of data will be the
=>responsibility of the Engineering Department.

Background

[][]Project Description & Related issues
[][]This air compressor system is installed to serve Cephalosporin and General Block. To meet the demand of quality compressed air this oil free air compressor will be installed.

Purchasing Information

ItemBrandModelOrigin
Air CompressorAtlas CopcoZT 75Belgium
DryerAtlas CopcoCD 185+Belgium
Air receiving tankAtlas CopcoN/AGermany
Piping and distributionFabricated N/ALocal

System Description

[][]The Atlas Copco Air Compressor and Air Dryer manufactured by Atlas Copco has a capacity of 10.4 m3/min. Air drawn through an air filter is compressed in low-pressure compressor element and discharged to the intercooler.

[][]The cooled air is further compressed in high-pressure compressor element and discharged through silencer and after coolers. A check valve is provided downstream of the silencer.

[][]The compressed air leaves the compressor via the air outlet. The compressor delivers oil-free, pulsation-free air.
[][]This is an air cooled type compressor which is facilitated with air filter, moisture trap, high pressure and low pressure safety valve, desiccant type dryer system etc.
[][]After being compressed in compressor the oil free compressed air will be stored in a receiver tank.

[][]Air will be dried in the desiccant type dryer and then distributed through pipe line to the different production facility.

Verification Of Installation

Drawings

[][]Physical installation of all the Compressed air related work has to be verified against reference drawings.

[][]The installations that will be found identical with the drawings will be marked by green color and those which will not match with the drawings will be marked by red/orange color.

Drawing DetailsDrawing TitleDrawing NumberDrawing Change Required
Yes/No
Initial with Date
Distribution of Compressed Air in Cephalosporin and General BlockDistribution of Compressed Air in Cephalosporin and General Block
Airflow SchematicsAir flow schematic Drawing for Atlas copco Air Compressor
Air Compressor Floor Plan drawingGeneral Building Roof Top
Electrical WorkElectrical diagram

Item Wise Verification

1.0 Air Compressor

2.0 Desiccant Dryer

3.0 Air Filter

4.0 Air Reservoir

5.0 General Installation Checking

6.0 Instrumentation

7.0 Utilities

All of the parameter has been depicted on assigned protocol.

Deviation And Failure Investigation Summary

In the column below, record any deviations or failures that occurred during the IQ exercise.

Report summary

The report summary of installation qualification of atlas copco air compressor of general block is as as described.

Conclusion

[][]The Installation Qualification of Atlas Copco Air Compressor installed at General Block Complies / Does Not Comply with the acceptance criteria taken above and the results obtained are attached with the protocol.
[][]The Atlas Copco Air Compressor of General Block is / is not qualifying the Installation Qualification test as per this Protocol. Hence, the system can be / cannot be used for Operational Qualification.

 

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Compressed Air Installation Qualification Protocol

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HVAC Operational Qualification

HVAC Operational Qualification, Purpose

HVAC Operational Qualification, To authenticate and document that the HVAC system of Sterile Production area of Cephalosporin Block of XX Pharmaceuticals Limited operates as per requirements and all the parameters of HVAC system meet the acceptance criteria of XX and manufacturer specifications.

HVAC Operational Qualification, Scope

This Operational Qualification (OQ) is to be performed against agreed acceptance criteria on the HVAC systems, comprising of Air Handling Units, Distribution / Return Ductworks, Chiller, Chilled Water Piping, Pumps, Control System etc. installed in the Cephalosporin Block of XX to serve the Sterile Production area of Cephalosporin Block.

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Responsibilities

[][]Protocol Preparation
[][]Validation (Engineering) Department of XX
[][]Protocol Execution
[][]Validation Team of XPL or other suitably qualified third party.
[][]Providing documentation on the equipment
[][]Related departments i.e. Engineering, Production, Validation, Microbiology department of PPL or other third party.
[][]Data documentation and preparation of the report
[][]Validation (Engineering) Department of PPL.

Project Description & Related issues

[][]The rooms of Sterile Production area have been classified as EU Class C and Class B. The air is supplied to the rooms of Class C area by AHU 2C.CE through three stages filtration by pre filter (G4), intermediate filter (F7 and F9) and finally HEPA (H14) filters.
[][]Furthermore, AHU 3B.CE supplies air to the class B area through 3 stages filtration such as pre filter (G4), intermediate filter (F7) and terminal filter (U15).

Operational Testing

Air flow verification

Test Method:
[][]Measure the supply air flow rate by using a flow hood. Assemble the flow-hood by firmly covering the whole supply diffusers. Open the flap of flow hood and switch on to get the readings of air flow.
[][]Set the flow-hood firmly to prevent air leakage over each individual supply air diffusers, HEPA filter and record the reading of the air flow volume in the result sheet.
Record the result in Appendix 1.

Acceptance Criteria:

[][]The air flow should be balanced throughout the area in such a way that it will produce an air volume not less than 10.00% of the design specification at each terminal.
[][]In some cases, exact air volume may be accepted at values lower or higher than 10.00% of design in order to meet room pressure requirements. Where the value is lower than the design, the value must be explained and justified.

Room Differential Pressure

Test Method:

[][]Prior to performing the test, verify that the design airflow volume tests have been carried out. HVAC system of the entire facility must be in continuous operation while performing this test.

[][]To avoid unexpected changes in pressure and to establish a baseline, all doors in the facility must be closed and no traffic is to be allowed through the facility during the test.

[][]Record the differential pressure from the calibrated magnehelic pressure gauge in the result sheet twice a day at rest and in operation conditions for three consecutive working days at each condition.
[][]Record the result in Appendix – 2.

Acceptance Criteria:

The acceptance criteria of differential pressure for each room have been stated in Appendix – 2.

Air change rate

Test Method:

[][]Measure the internal dimensions of each room and calculate the room volume.

[][]Calculate the total air supply to each room by summing the air supply from the individually measured HEPA filters or diffusers in above.

[][]Then calculate the number of air changes per hour for each room using the following formula:

=>Air change rate = Total measured room supply (m3/h)/ Measured room volume (m3)

Record the results in the result sheet in Appendix 3.

Acceptance Criteria:

[][]With reference to the previous section of ISPE Baseline Guide: Sterile Manufacturing Facilities the Air Change rate in all Classified area must be minimum 20.

Temperature and relative humidity

Test Method:

[][]Verify completion of HVAC system testing, adjusting and balancing work prior to performing these tests.

[][]Place calibrated thermometer/sensor and humidity device/sensor at the Return Air Grill.

[][]Allow time for the sensors to stabilize sufficiently for accurate readings.
[][]Measure the temperature and relative humidity at each processing room, twice a day under ‘at rest and in operation’ conditions for three consecutive working days each. Record the results in Appendix 4 and 5.

Acceptance Criteria:

[][]Temperature: 22deg.C±2deg.C for SPR058, SPR058, SPR066, SPR079 and NMT 25deg.C for other rooms in B area.
[][]NMT 25deg.C for C area.
[][]Relative Humidity (RH): NMT 30% for SPR058, SPR058, SPR066, SPR079 and NMT 55% for other rooms in B area.
[][]There is no limit of RH (%) in Grade C area as there will be no handling of Raw materials.

Particle count test

Test Method:

[][]Measure the particle count according to the procedure described in SOP and the printed data are attached with the report.
[][]Using the particle analyzer, count particles greater than or equal to 0.5 micron and also 5 micron in diameter at 1 m height at predefined number of positions in each room.
[][]The test will be performed for both at rest and at operation conditions and for three consecutive working days at each condition.
[][]The report is given from the Microbiology department which will be attached with the report.

Microbial count test:

Test method:

[][]Air borne microbial test is to be done according to the procedure described in SOP and the data are attached with the report.
[][]The test will be performed at rest and in operation conditions for three consecutive working days at each condition.
[][]All the results must be recorded on the appropriate forms of monitoring methodology.
[][]The limits of sterile and non sterile applications are recorded below.
[][]The report will be provided from the Microbiology department which will be attached with the report.

Clean up time or Recovery Test

Test Method:

[][]The recovery test is performed by………………according to the SOP No. …………. The results are recorded in Appendix – 6. The test will be performed only for the rooms where HEPA filter is installed in the supply terminal.

Acceptance Criteria:

[][]Clean up time will NMT 20 minutes. The “clean up” or “recovery” test should demonstrate a change in particle concentration by a factor of 100 within the specified time (according to ISO 14644-3 clause B.12).

Filter Integrity Test

Test Method:

[][]The test will be performed by……………………………..according to the SOP No. …………………………………..The copy of the test report is attached with the report.

Acceptance Criteria:

[][]Any leakage greater than 0.01% for H14 respectively of the upstream challenge aerosol concentration is considered unacceptable. HEPA Filter test report to be recorded in the Attachment.

Smoke test

Test Method:

=>The test will be performed by _______________________ according to the SOP No. ________________.

Acceptance Criteria:

[][]All the processing rooms are at positive pressure with respect to the adjacent corridor.

[][]Furthermore, in case of any two adjacent rooms of different classified areas, the higher classified area will be at positive pressure.

[][]So, the smoke will flow from positive to negative areas.

Instrument Calibration

=>The necessary instruments to complete the OQ of HVAC system of Sterile Production area of Cephalosporin Block is listed below:

Sl. No.Instrument TypeID No.Calibration DateCalibration Due DateCertificate No.Initial & Date
01Thermo hygrometerCC-000-000-TMH-001
02Differential Pressure ProbeCC-000-000-PID-001 with B1
03Aerosol Photometer

Deviation And Failure Investigation Summary

=>Record in the column below any deviations or failures that occurred during the OQ exercise.

Report Summary

=>The report summary of Operational Qualification of HVAC system of Sterile Production area of Cephalosporin Block Is as found.

Conclusion

[][]All / Some testing parameters of the Operational Qualification of HVAC system of Sterile Production area of Cephalosporin Block Comply / Do Not Comply with the acceptance criteria and the results obtained are attached with the protocol.
[][]The HVAC system of Sterile Production area of Cephalosporin Block is / is not qualifying the Operational Qualification test as per this protocol after proper justification of the deviation (if found). Hence, the system can be / cannot be used for production operation.

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HVAC Operational Qualification Protocol

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Pure Steam System Performance Qualification

Pure Steam Performance Qualification , Purpose

Pure Steam Performance Qualification , To determine that the Pure steam generator performs as per the given specifications, by running the system on its intended schedules and recording all relevant data under normal conditions & for worst-case situations where applicable.

Pure Steam Performance Qualification , Scope

This Performance Qualification (PQ) is to be performed against agreed acceptance criteria on the pure steam generator system Cephalosporin Block of XX Pharmaceuticals Ltd. The scope will include the measurement of Non-condensable gases, superheat value, dryness value and microbiological test of pure steam system.

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Responsibilities

[][]Preparation of the protocol
=>Validation (Engineering) Department with the assistance of Microbiology, Quality Assurance and Engineering department.

[][]Executing the protocol
=>Validation team along with respective departmental person and engineers or other suitably qualified staffs allocated from the site or contracted specialists as appropriate.

[][]Non-condensable gas, superheat value, dryness fraction
=>Validation (Engineering) Department

[][]Microbiological Test
=>Microbiology Department

[][]Data documentation and preparation of the report
=>Validation (Engineering) department.

[][]Verifying of the report
=>Concerned departmental person.

[][]Providing documentation on the equipment
=>Related departments i.e. Engineering, Production, Microbiology, Validation or other appropriate departments and manufacturer.

System And Process Description

=>System Information
=>Manufacturer : Watertown
=>Capacity : 200kg/hr
=>Model : MS750/4T
=>Serial No. : MS1132

Reference Instruments

=>Name : Steam quality test kit
=>Manufacturer : Dekon Solutions, UK
=>Model : SQ kit Option – A.

The System under test

[][]The pure steam is generated in the WFI plant located at the roof top utility area of Cephalosporin Block. Industrial steam enters into the first heat exchanger of WFI plant and exchanges heat with the purified water and is converted into pure steam. Therefore, pure steam is supplied at a pressure of around 2.5 bar – 4 bar to the autoclave room of sterile area of cephalosporin block.

Performance Tests

[][]The tests for performance qualification of pure steam as follows:

=>Non-condensable gas test
=>Test Method

[][]The measurement of non-condensable gases is made by cooling a steam sample, using water through an efficient condenser.
[][]Water can be supplied either directly from a pressurized supply or simply by siphoning from a tank at a flow rate of 200ml/minute, provided that a minimum head of 1.0 meter is maintained and at a temperature not exceeding 250C.
[][]When the sampled steam is condensed, any non-condensable gases that may be present are liberated and separated from the produced condensate into two sight glass columns.
[][]The gas and steam condensate volumes are measured by the ‘zero adjustable’ scale mounted behind the two sight glasses.
[][]Perform the test for 3 consecutive working days.
[][]Record the result in Appendix 1.

 Acceptance Criteria

[][]The results of the non-condensable gas test are deemed to be acceptable for sterilization purposes if the percentage of gas to condensate is less than 3.5%.
[][]Observations:
[][]Done by: Checked by:

Steam Superheat Value

Test Method
[][]The temperature of steam passing through an orifice in a pitot tube is measured.
[][]The temperature is measured by using a thermocouple which is located at the centre of the expansion tube placed over the pitot tube.
[][]The test is intended to demonstrate that the amount of moisture in the steam supply is sufficient to prevent the steam from being superheated as it enters the expanded space of a sterilizer chamber.
[][]Perform the test for 3 consecutive working days.
[][]Record the result in Appendix 2.

Acceptance Criteria

The temperature of the pure steam is considered to be acceptable if it is less than 250C above that of the local temperature of boiling water, which is altitude dependent.

Pure Steam Dryness Value

Test Method

[][]The purpose of the steam dryness value test is to ensure that an acceptable amount of moisture is present in the steam supply. If too little moisture were present, superheating of the steam may occur.

[][]Too little moisture may also prevent the optimum sterilization conditions occurring within the sterilizer load because, moisture is the critical factor breaking down the cell structure of sporing organisms.

[][]The method employed is the heat balance using a stainless steel vacuum flask. The principal being that the flask is primed with a known mass of water at a known temperature.

[][]Steam is then condensed in the flask thus raising the temperature of the water. When the final mass and temperature of the water are measured and placed to the excel worksheet, provided by the manufacturer of the Steam Quality Test Kit, the dryness value is calculated.
[][]Perform the test for 3 consecutive working days.
[][]Record the results in Appendix 03.

Acceptance Criteria

=>The Pure Steam Dryness Value must be within 0.9 – 0.95.

Chemical tests

Test Method

[][]Three tests will be performed as chemical tests such as Appearance test, conductivity as well as TOC. The pure steam will be collected in a depyrogenated flask and the chemical tests would be performed for the condensate of the pure steam. Wear hand gloves and goggles while collecting the sample.
[][]Perform the test for 3 consecutive working days.
[][]The results will be provided from the Quality Control department in the respective forms and will be attached with the report.

Acceptance Criteria:

=>The specifications of these tests according to QC/SPEC/RMEXXX/01:

TestsAcceptance Limit
AppearanceClear, colorless and odorless liquid.
ConductivityNot more than 1.1µS.cm-1 at 200C
Or
Not more than 1.3µS.cm-1 at 250C
TOCNot more than 0.5 mg/L

Microbiological tests

Test Method

[][]Microbiological tests will be performed by collecting the pure steam in a depyrogenated flask. Wear hand gloves and goggles while collecting the sample.
Perform the test for 3 consecutive working days.
[][]The results will be provided from the Microbiology department in the respective forms and will be attached with the report.

Acceptance Criteria:

The specifications of these tests according to QC/SPEC/RMXXX/01:

TestsAcceptance Limit
Total viable Microbial CountNot more than 10 CFU/100mL.
E.ColiMust be absent
Staphylococcus aureusMust be absent
Pseudomonas aeruginosaMust be absent
Salmonella sppMust be absent
Bacterial EndotoxinsLess than 0.25 EU/ml

Sampling Points and Test Frequency

The list of sampling points which come into product contact is given below:

Sl. No.Sampling point nameRoom No.BlockRoom NameTestsFrequency
01PS – 01SPR0XXCephalosporinAutoclaveNon-condensable gas, steam superheat value, steam dryness factor, chemical and microbiological tests.6 months.

Deviation And Failure Investigation Summary

[][]In the column below, record any deviation or failure that occurred during the PQ exercise.

Report Summary

The report summary of performance qualification of Pure Steam system shall be mention here.

Conclusion

The Performance Qualification of the Pure Steam system of Cephalosporin Block Complies / Does Not Comply with the acceptance criteria taken above and the results obtained are attached with the protocol.
The Pure Steam system is / is not qualifying the Performance Qualification test as per this Protocol. Hence, the system can be / cannot be used for production operation.

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Performance Qualification of Pure Steam Protocol

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Vial Filling Machine Performance Qualification

Vial Filling Machine Performance Qualification, Purpose

[][] Vial Filling Machine Performance Qualification, The purpose of this protocol is to provide an outline for the Performance Qualification of Vial/Vial Filling Machine to:
=>Demonstrate that the system performs as intended by repeatedly running the system on its intended schedules under normal operating conditions and worst-case conditions, where appropriate.
=>To assess the machine capability to fill consistent volumes at various running speed.
=>To check the stoppering of vials.
=>To check the presence of any particulate matter visually.

Vial Filling Machine Performance Qualification, Scope

[][]The aim of this qualification is to perform the performance qualification of the following machine. It is documented evidence that the machine installed properly and functions correctly in accordance with the desired specification as well as manufacturer’s information. It also certifies that the machine operates reliably and within prescribed or specified operating limit. This protocol covers the following machine:

=>Equipment Name

=>Machine No.

=>Location

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Responsibility

[][]Protocol preparation as per the guideline of Validation Master Plan
=>Validation Dept.
[][]Check & review of the protocol
=>Validation & Technical Expert*
[][]Approval of protocol prior to execution
=>Head of Validation, QA, Engg., Plant
[][]M/C operation , testing and data processing
=>Validation team
[][]Microbiology challenge test
=>Microbiology
[][]Preparation of report
=>Validation Dept.
[][]Check & review of the report
=>Validation & Technical Expert*
[][]Approval of the qualification report
=>Head of Validation/QA/Engg./Plant
[][]Authorization of the report
=>Director, Technical Operations
[][]Protocol preparation as per the guideline of Validation Master Plan
=>Validation Dept.

System and process Description

The Vial filling and stoppering machine is used to fill and stopper the vials. The machine consists of following parts:

Line 1:
[][]This line is a compact filling line with capacity to fill around 6000 Vials/ hr. This machine can fill from 0.3 ml to 2.1 ml. In brief its function is as follows:
[][]The vials are fed upright from a depyrogenation tunnel connected to upstream on to an in feed rotary table.
[][]This table rotates continuously and guides the vials with various deflectors through two infeed lanes into the walking beam transport system.
[][]There are two sensors attached in each lane to detect fallen containers, which after detection goes to bin.
[][]These containers are stopped by two infeed gates.
[][]If there are enough containers in the in feed tracks the container feed sensors at the in feed are actuated and infeed gates open.
[][]The walking beam advances the containers intermittently to various work station where two containers are processed at each machine cycle as per following sequence:

Nitrogen flushing=>Filling=>Nitrogen flushing =>Stoppering=>Discharge=>stopper Checking =>Visual Inspection=>Confirmation

Machine consists of following parts:.
Infeed Rotary Table —

[][]The containers are placed upright on the infeed rotary table by the machine upstream- The containers are conveyed continuously until they are stopped by infeed gates.
[][]There is ultrasonic sensor on table which detects Quantity of containers on the table.
[][]If too many containers accumulate on table then sensor give message to tunnel to reduce the speed of tunnel automatically.
[][]When Quantity is reduced , automatically tunnel increase its speed.

Container feed tracks and monitoring –

[][]The containers from above table are feed into two tracks, where they pass an outlet in the rim of table where fallen containers roll out into a bin beneath the rotary table.
[][]A sensor is located in each feed track. If the container supply in one of the track is very much low , then infeed gates closes, so no further container enter the machine from this track.
[][]When the supply replenish the gates reopen.

Infeed gates

[][]The containers arriving in the infeed tracks are stopped by the infeed gates and are prevented from entering the walking beam.
[][]When the infeed gates are switched on at the operating panel, each gate opens to let containers into transport system provided that the respective container feed sensor detect sufficient containers in the track.

Container Registration sensor

[][]This detect the containers in walking beam and transform information to machine cycle to start the process.
[][]If no container is detected then work station is blocked automatically.

Walking beam transport System –

[][]This system transport the vials through the machine.
[][]They are conveyed upright on a base guide between walking beam and the counterguide.
[][]This walking beam consist of two parts : one part centers the vials and the other one transport them.

Liquid dosing unit –

[][]The product is filled by 2(two) rotary piston pump. The amount dispensed is virtually proportional to the pump stroke.

[][]As the pump piston rise. Product is drawn from the manifold to the pump via hoses.

[][]The piston then turns through 180°, so that the grooves are directed towards the filling needle.
[][]As the pistons are lowered, the product is discharged through dosing hoses and filling needle in to the vials.
[][]This dose can be adjusted by altering the pump stroke.

Gas-flushing Equipment –

[][]Two needles for pre flushing and two needle for post flushing are provided in this system.
[][]The gas flushing needles are lowered in containers with the filling needle movement and flush the container interior with 0.2µ filtered Nitrogen, thereby displacing the ambient air from the container.

Stopper insertion station –

[][]At this station the rubber stoppers are placed on the neck of containers and then pressed in.
[][]The vacuum required for the insertion station is provided by inbuilt vacuum pump.
[][]This station consists of Stopper feed, sorting bowl filling level monitor, Feed track monitoring, stopper check sensors, discharge wheel and tray loading unit.

Line-2:

[][]This line is a compact filling line with capacity to fill around 12000 ampoules/ hr. It has ampoule sealing machine also. This machine can fill from 0.3 ml to 2.1ml. In brief its function is as follows:
[][]The Ampoules are fed upright from a Depyrogenation tunnel connected to upstream on to a in feed belt.
[][]At the end of belt the ampoules are picked by the feed scroll, spaced by the recesses of the scroll and pushed into the individual transport recesses around the periphery of star wheel.
[][]The star wheel conveys the ampoules in a continuous movement and present to individual work stations.
[][]The rotation discs located at the work stations rotate the ampoules during all the work process to ensure smooth functioning of each step.
[][]All the work stations move forward synchronously with the containers during ampoule processing and swivel back to initial position after end of process.
[][]Four ampoules are processed at each machine cycle with following sequence:

Nitrogen flushing=> Filling =>Nitrogen flushing =>Heating of tips of Ampoules =>Sealing by Fusing =>Pulling of Ampoule tips=>Discharge

Machine consist of following parts:.

Infeed belt

[][]The containers are placed upright on the infeed belt by the machine upstream.
[][]If too many containers accumulate on belt then sensor give message to tunnel to reduce the speed of tunnel automatically.
[][]When Quantity is reduced, automatically tunnel increase its speed.
[][]If no container arrive from tunnel, then infeed scroll of AFV stops, preventing any further ampoules from entering the star wheel.

Container Registration sensor

[][]Before each transport recess on the star wheel reaches the first work station, a light sensor checks for the presence of Ampoule.
[][]If ampoule is detected, the pulse emitted by the photoelectric sensor is memorized in electronic control and this information is transferred for running all machine cycles.
[][]If no ampoule is detected then work stations are blocked automatically..

Liquid dosing unit

[][]The product is filled by 4(Four) rotary piston pump. The amount dispensed is virtually proportional to the pump stroke. As the pump piston rise.
[][]Product is drawn from the manifold to the pump via hoses.
[][]The piston then turns through 180°, so that the grooves are directed towards the filling needle.
[][]As the pistons are lowered, the product is discharged through dosing hoses and filling needles in the ampoules.
[][]This dose can be adjusted by altering the pump stroke.

Gas-flushing Equipment

[][]Four needles for pre flushing and Four needle for post flushing are provided in this system.
[][]The gas flushing needles are lowered in Ampoules with the filling needle movement and flush inside the Ampoule interior with 0.2µ filtered Nitrogen, thereby displacing the ambient air from the Ampoule.

Line 3 :

[][]This line is a compact filling line with capacity to fill around 6000 vials/ hr.
[][]It is also set for full stoppering as this line is only for liquid filling.
[][]This machine can fill from 0.3 ml to 2.1 ml. This machine is same as line 1.

Line 4:

[][]This line is a standalone filling line with capacity to fill around 6000 vials/ hr.
[][]It is also set for full stoppering as this line is for liquid filling.
[][]This machine can fill from 0.7 ml to 5.5 ml and 8 ml to 50 ml.
[][]In this machine the vials are sterilized in Dry Heat sterilizer in trays and are feed manually to machine.

Tests To Be Performed and Planned

Sl.NoTestPlan/Frequency
01Consistency in fill volume at various speedConsecutive 3 runs
02Proper StopperingConsecutive 3 runs
03Check of presence of any particulate matterConsecutive 3 runs

Test Details and Records

Consistency of Filled Volume

[][]The vial filling machine is started at a main drive motor speed of 100% and after 15 minutes 10 vials are collected to check the consistency of filled volume.
The same procedure is repeated for 90% and 80% main drive motor speed.
[][]Result is recorded in the result sheet form.

Record of consistency of filled volume

=>Media used for filling
=>Vial Size

ParticularsRun 1 Date:Run 2 Date:Run 3 Date:
No. of 3ml vials to fill at main drive motor speed of 100%
Average volume of 10 Vials at 15 Minutes after start
No. of 3ml vials to fill at main drive motor speed of 90%
Average volume of 10 Vials at 15 Minutes after start
No. of 3ml vials to fill at main drive motor speed of 80%
Average volume of 10 Vials at 15 Minutes after start

Acceptance Criteria:  The filled volume has to be within 10ml ± 0.5ml.

Check of Stoppering

[][]In each run 20 vials are collected to visually check the stoppering.

Result of checking stoppering

Run no.DateNo. of properly stroppered vialsNo. of not properly stroppered vialsPercentage of rejected vials

Acceptance Criteria:   The number of rejected vials has to be less than 1.0%.

Check of presence of any particulate matter

[][]In each run 20 vials are collected to check the presence of any visible particulate matter.

Result of checking presence of any particulate matter

Run no.DateNo. of total filled vialsNo. of rejected vialsPercentage of rejected vials

[][]Acceptance Criteria:   The number of rejected vials has to be less than 1.0%.

Report Summary

[][]The Performance Qualification study for Vial/Vial Filling machine was carried out for 3 consecutive date and following result summary was obtained.

No.TestsAcceptance limitsRun 1
Passed (Y/N)
Run 2
Passed (Y/N)

Run 3
Passed (Y/N)

01Consistency in fill volume at various speedNMT 0.5ml Variation from adjusted Limit
02Proper Stoppering99% Complies
03Check of presence of any particulate matter.99% Complies

The Result of this Performance Qualification study was recorded, summarized and analyzed. The observed parameters/tests and subsequent analytical results show that the vial filling machine perform as per predetermined acceptance criteria. Hence, the machine successfully qualifies the performance Qualification test.

Conclusion

The performance qualification complies with the acceptance criteria taken above and the results obtained are attached to the protocol.

Vial/Vial Filling Machine bearing Equipment ID No. ……….………….Is / Is Not qualifying the Performance Qualification test as per the guideline described in this Protocol No. ————- and Can Be / Cannot Be use for production.

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Vial Filling Machine Performance Qualification Protocol

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Cartridge Filling Machine Performance Qualification

Cartridge Filling Machine Performance Qualification, Purpose

[][]Cartridge Filling Machine Performance Qualification, The purpose of this protocol is to provide an outline for the Performance Qualification of Vial/Cartridge Filling Machine to:
[][]Demonstrate that the system performs as intended by repeatedly running the system on its intended schedules under normal operating conditions and worst-case conditions, where appropriate.
[][]To assess the machine capability to fill consistent volumes at maximum and minimum running speed.
[][]To verify the gliding force of filled cartridges.
[][]To ensure proper stoppering.
[][]To check the air bubble size with respect to glass bead size.

Cartridge Filling Machine Performance Qualification, Scope

[][]The aim of this qualification is to perform the performance qualification of the following machine. It is documented evidence that the machine installed properly and functions correctly in accordance with the desired specification as well as manufacturer’s information.
[][]It also certifies that the machine operates reliably and within prescribed or specified operating limit. This protocol covers the following machine:

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Vial Filling Machine Performance Qualification Protocol

Responsibility

[][]Validation Dept.
Protocol preparation as per the guideline of Validation Master Plan
[][]Validation & Technical Expert*
Check & review of the protocol
[][]Head of Validation, QA, Engg., Plant
Approval of protocol prior to execution
[][]Validation team
M/C operation , testing and data processing
[][]Microbiology
Microbiology challenge test
[][]Validation Dept.
Preparation of report
[][]Validation & Technical Expert*
Check & review of the report
[][]Head of Validation/QA/Engg./Plant
Approval of the qualification report
[][]Director, Technical Operations
Authorization of the report
[][]Validation Dept.
Protocol preparation as per the guideline of Validation Master Plan

System and process Description

[][]The Cartridge filling and stoppering machine is used to fill and stopper the Cartridges. The machine consists of following parts:
[][]This line is a compact filling line with capacity to fill around 2500 cartridges/ hr. The cartridges are fed upright from a depyrogenation tunnel connected to upstream on to an in feed rotary table.
[][]There is a vibrator by which this table is vibrated continuously and guides the cartridges with various deflectors through infeed lanes into the filling portion. There is a sensor to detect fallen containers.
[][] If there is any fallen cartridge, it shows alarms on the display and the machine is stopped. If there are enough containers in the in feed tracks the container feed sensors at the in feed are actuated and infeed gates open. After coming through the in feed rotary screw the glass beads are inserted into the cartridges.
[][]There are two rotary piston pumps for transferring the filling media from vessel to the two filling nozzles. First nozzle is for filling half of the required volume and second one is for remaining half.
[][] There is a nozzle for sucking the access media at the 2nd filling nozzle. The filling volume is virtually proportional to the stroke of the piston pumps.
After filling, the flip off seals are attached at the top of the cartridges.
[][]There is a container for flip off seals and these are transferred by using the vibration. A proximity sensor detects the presence of flip off seals.
[][]The whole process occurs under a Laminar Air Flow Unit which ensures a clean area of Class A (ISO Class 5). The flow diagram of filling machine is as follows:

Tests To Be Performed and Planned

SR./NO.TestPlan/Frequency
01Consistency in fill volume at various speedConsecutive 3 runs
02Gliding force measurement for filled cartridges.Consecutive 3 runs
03To check the bubble size with respect to size of Glass beads.Consecutive 3 runs
04To check proper stoppering.Consecutive 3 runs

Test Details and Records

Consistency of Filled Volume

[][]The cartridge filling machine is started at a main drive motor speed of 100% and after 15 minutes 10 cartridges are collected to check the consistency of filled volume.
[][]The same procedure is repeated for 90% and 80% main drive motor speed.
[][]Result is recorded in the result sheet form.

Record of consistency of filled volume

Cartridge SizeRun 1
Date:
Run 2
Date:
Run 3
Date:
No. of 3ml cartridges to fill at main drive motor speed of 100%
Average volume of 10 Cartridges at 15 Minutes after start
No. of 3ml cartridges to fill at main drive motor speed of 90%
Average volume of 10 Cartridges at 15 Minutes after start
No. of 3ml cartridges to fill at main drive motor speed of 80%
Average volume of 10 Cartridges at 15 Minutes after start

Acceptance Criteria: The filled volume has to be within 3ml ± 0.3ml.

Gliding Force for Filled Cartridges

[][]10 cartridges are marked and loaded with the cartridges of total batch.
[][]After filling and stoppering 10 filled cartridges are collected at 15 minutes after starting the machine at a speed of 100% of main motor.
[][]The procedure is repeated twice by varying the speed to 90% and 80% of the main motor.

Record of Gliding Force for Filled Cartridges

Run no.Gliding Force Measuring Machine SpecificationDateAverage Gliding Force
(Newton)
Met Acceptance Criteria (Y/N)
01
02
03

Acceptance Criteria: The gliding force has to be less than 20N.

Bubble Size

[][]In each run 20 cartridges are collected to visually check the presence of glass beads and the bubble size with respect to glass bead size.

[][]Result of checking bubble size

Run no.DateGlass bead present (Y/N)Bubble present (Y/N)Bubble size is smaller than glass bead size (Y/N)Percentage of rejected cartridges

Check of Stoppering

In each run 20 cartridges are collected to visually check the stoppering.

Result of checking stoppering

Run no.DateNo. of properly stroppered cartridgesNo. of not properly stroppered cartridgesPercentage of rejected cartridges

Acceptance Criteria: The number of rejected cartridges has to be less than 10%.

[][]List of Reference Involved in Validation Study

[][]Details Of Attachments To Validation Report

Report Summary

The Performance Qualification study for Vial/Cartridge Filling machine was carried out for 3 consecutive date and following result summary was obtained.

No.TestsAcceptance limitsRun 1
Passed (Y/N)
Run 2
Passed (Y/N)
Run 3
Passed (Y/N)
Consistency in fill volume at various speedNMT 0.3ml Variation from adjusted Limit
Gliding force for filled cartridgesGliding Force for filled cartridges has to be less than 20 Newton.
Bubble SizeBubble size has to be less than glass beads size.
Proper Stoppering99% Complies

[][]The Result of this Performance Qualification study was recorded, summarized and analyzed. The observed parameters/tests and subsequent analytical results show that the cartridge filling machine perform as per predetermined acceptance criteria. Hence, the machine successfully qualifies the performance Qualification test.

Conclusion

[][]The performance qualification complies with the acceptance criteria taken above and the results obtained are attached to the protocol.

[][]Vial/Cartridge Filling Machine bearing Equipment ID No. ……….………….Is / Is Not qualifying the Performance Qualification test as per the guideline described in this Protocol No. ————- and Can Be / Cannot Be use for production.

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Performance Qualification of Cartridge Filling Machine Protocol

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Depyrogenation Tunnel Performance Qualification

Depyrogenation Tunnel Performance Qualification, Purpose

Depyrogenation Tunnel Performance Qualification, To authenticate and document that the performance of the Depyrogenation Tunnel of Sterile Production area (Cephalosporin Block) of XX Pharmaceutical Limited (PPL) is satisfactory in all critical aspects related to the operational requirements. This protocol describes the performance qualification procedures of the Depyrogenation Tunnel manufactured by Tofflon, China.

Depyrogenation Tunnel Performance Qualification, Scope

This Performance Qualification (PQ) is to be performed against agreed acceptance criteria on the vials of three sizes such as 7.5 ml, 15 ml and 30 ml, which will be sterilized by the Depyrogenation Tunnel installed in the Sterile Production area of Cephalosporin Block of XX Pharmaceutical Limited.

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Autoclave Performance Qualification Protocol

Responsibilities

Preparation of the protocol

[][]Validation (Engineering) Department with the assistance of Microbiology, Engineering and Maintenance department.

Executing the protocol

[][]Validation (Engineering) Department along with respective departmental person and engineers or other suitably qualified staff allocated from the site or contracted specialists as appropriate.

Microbiological Challenge Test

[][]Microbiology department

Data documentation and preparation of the report

[][]Validation (Engineering) department.

Verifying of the report

[][]Concerned departmental person.

Providing documentation on the equipment

[][]Related departments i.e. Engineering, Production, Microbiology, Validation or other appropriate departments and manufacturer.

Equipment Information

=>Manufacturer : Tofflon, China
=>Capacity : 6000-9000 vials /hr
=>Model : SZA 620
=>Serial no. : YF2014-078B

The Equipment under test

[][]The Depyrogenation tunnel under validation study has the following segments:
=>Pre-heating zone
=>Sterilization zone
=>Cooling zone
[][]The whole production process combines in a line consecutively with a Vial washing machine, Depyrogenation tunnel, Vial Filling machine and Cap sealing machine.

[][]The washed Vials are conveyed into the Pre-heating Zone of the Depyrogenation tunnel automatically after washing in the vial washing machine.

[][]The Vials are flooded with sterile air in this zone. The temperature controlling preset values maintain the circulating air temperature at that preset value.

[][]The warm Vials are then transported into the Sterilizing Zone and are sterilized & depyrogenated by a low turbulence air flow (up to 300°C). The air is heated in an air circulation duct and then flows through the high temperature HEPA filters prior to reaching the vials.

[][]These filters ensure that the air quality corresponds to clean room class A (class 5 according to ISO 14644) in all operation modes, even in the heating and cooling phases. In the last work zone (cooling zone) of the tunnel, the sterilized Vials are cooled down by a vertical low turbulence air flow.

[][]The discharge from the tunnel opens into a clean room where the depyrogenated Vials are stored on a turn table and conveyed by belt transfer system to the infeed of filling machine.

Checking Parameters

[][]The PQ of Depyrogenation Tunnel will be carried out to evaluate the following conditions to confirm the sterilization conditions:
=>Heat Penetration (HP) studies.
=>Microbiological Challenge (MC) test using Endotoxin Challenge Vials.

The system/ equipment to be used as Standard for testing

[][]Performance of the Depyrogenation Tunnel will be judged based on thermal and biological studies which are mentioned below:
=>Equipment Name: Anville Data Logger, TQ Soft Version 6.1.2 with thermocouples.
=>Requirement for challenge test: -Endotoxin Challenge Vials.

Pre requirement For Validation:

[][]Calibration of thermocouples of the data logger/Validator before and after validation with proper identification.
[][]Valid calibration record of Data Logger/Validator.
[][]Data logger reading intervals set at 30 seconds (maximum).
[][]Successful calibration of the Temperature sensors of Depyrogenation Tunnel.
[][]Successful completion of IQ and OQ.
[][]Endotoxin Challenge Vials for ensuring 3 log reduction.

Study Procedure:

Heat Penetration (HP) Study:

[][]The equipment must be run three times at fully loaded condition for each size of vial where seven thermocouples are exposed to monitor the temperature within the loads.
[][]The number of measurement points will be dependent of the width of the tunnel. As the width of the tunnel is 590 mm, seven thermocouples will be placed at 98 mm distance from each other as shown in Appendix – 01.
[][]The conveyer belt of the tunnel will be run at about 98.4 mm/min and 90.2 mm/min for 7.5ml, 15ml and 30 ml vials respectively.
[][]Care must be taken to avoid contact between the thermocouples and the metal surface of the chamber. Evenly distribute the thermocouples as it is shown in the Appendix – 01.
[][]The Results of this test will be recorded in the Appendix-03 (Number of this appendix will be increased as per number of cycles) and will be accepted if met the acceptance criteria.

Microbiological Challenge (MC) test:

[][]This test will be performed while performing the HP study. Seven Endotoxin challenge Vials (ECV) are distributed along with the thermocouples at defined positions of conveyer belt of tunnel at fully loaded condition as per specified load pattern as specified in Appendix -1.
[][]After completion of the cycle ECVs will be tested by the microbiology department for required log reduction.
[][]The results of above test should be recorded in the designated form (Appendix-4).

Acceptance Criteria

For Heat Penetration (HP) study:

[][]During sterilization period; all thermocouple readings must be within set temperature (300deg.C)±15deg.C.
[][]During sterilization period; when all thermocouples are showing a minimum of 285deg.C, temperature difference among the thermocouples are not more than 15deg.C.
[][]For cooling zone performance study:
[][]After passing sterilization zone, minimum reading of all thermocouples are below 35deg.C.

For Microbiological Challenge Test:

[][]The ECVs not exposed to the Depyrogenation cycle (control) should show clot after incubation at time and temperature as per COA.
[][]The Endotoxin content of a challenge vial must be reduced at least 1000 fold (> 3 log reduction).

Deviation And Failure Investigation Summary

In the column below, record any deviations or failures that occurred during the PQ exercise.

Deviation/ Failure No.Description and Assessment of Impact on ValidationInitialDate
1
2
3

Reference Documents

[][]FDA Guidance for Industry ( for the Submission Documentation for Sterilization Process Validation in Applications for Human and Veterinary Drug Products).

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Autoclave Performance Qualification Protocol

Autoclave Performance Qualification Protocol, Purpose

Autoclave Performance Qualification Protocol, To authenticate and document that the performance of the Autoclave (Steam sterilizer) of Sterile Production area (Cephalosporin Block) of XX Pharmaceutical Limited (LPL) is satisfactory in all critical aspects related to the operational requirements during sterilization of porous, solid and liquid loads. This protocol describes the performance qualification procedures of the Autoclave manufactured by Zirbus, Germany.

Autoclave Performance Qualification Protocol, Scope

This Performance Qualification (PQ) is to be performed against agreed acceptance criteria on different types of loads which will be sterilized by the Autoclave (Steam Sterilizer) installed in the Sterile Production area of Cephalosporin Block of XX Pharmaceutical Limited.

[][]Preparation of the Protocol
Validation (Engineering) Department with the assistance of Microbiology, Engineering and Maintenance department.
[][]Executing the protocol
Validation (Engineering) Department along with respective departmental person and engineers or other suitably qualified staff allocated from the site or contracted specialists as appropriate.
[][]Microbiological Challenge Test
Microbiology department
[][]Data documentation and preparation of the report
Validation (Engineering) department.
[][]Verifying of the report
Concerned departmental person.
[][]Providing documentation on the equipment
Related departments i.e. Engineering, Production, Microbiology, Validation or other appropriate departments and manufacturer.

People Also Read

Depyrogenation Tunnel Performance Qualification Protocol

System and process Description

Equipment Information

=>Manufacturer : ZIRBUS, Germany
=>Capacity : 702 Ltr.
=>Model : HST 6×6×12
=>Serial no. : 3609

The Equipment under test

[][]The autoclave under validation study is a double door horizontal autoclave; chamber is made of SS 316L. The product is fed into the chamber via a loading port and drawn off after the sterilization cycle via the discharging port in a clean room of Grade B.
[][]A chamber leak test is performed to ensure that there is no leakage. It is very important to remove the air from the chamber. A water ring vacuum pump is used to remove the air from the chamber.
[][]For porous loads pre vacuum is important to remove the air pockets from the pores of the loads. To remove residual air vacuum pulse followed by steam pulse is used. After completion of vacuum and steam pulse the chamber is heated up with pure steam to the set sterilization temperature.
[][]There are two temperature sensors of which one is set inside the chamber and another is set in the drain port of the chamber. When the solid cycle is run, the drain temperature sensor controls the cycle. On the other hand, when the liquid cycle is run, the product temperature sensor controls the cycle

Checking Parameters

The PQ of autoclave will be carried out to evaluate the following conditions to confirm the sterilization conditions:
=>Chamber Leak Test (LT).
=>Bowie-Dick (BD) test.
=>Heat Penetration (HP) studies.
=>Microbiological Challenge (MC) test using Biological Indicators (BI).

The system/ equipment to be used as Standard for testing

Performance of the autoclave will be judged based on thermal and biological studies which are mentioned below:
=>Equipment Name: Anville Data Logger, Series 825 NATO.
=>Software: TQ Soft version 6.0

Requirement for challenge test:

=>Bowie-Dick test pack
=>Biological Indicator
[][]After completion of the cycles, all individual cycle records are summarized and compared with the autoclave printouts to verify the cycle consistency and performance.
[][]For Biological studies, Biological Indicators will be placed along with probes and will be studied for microbiological challenge test.

Pre requirement For Validation:

[][]Calibration of thermocouples of the data logger/Validator before and after validation with proper identification.
[][]Valid calibration record of Data Logger/Validator.
[][]Data logger reading intervals set at 30 seconds (maximum).
[][]Successful calibration of the Pressure and Temperature sensors of autoclave.
[][]Successful completion of IQ and OQ of Autoclave.
[][]Tubes of Geobacillus Stearothermophilus spores will be used as biological indicators. They should be labeled and placed at the front, middle and back of the autoclave chamber.

Study Procedure:

Chamber Leak (CL) Test:

[][]Thermocouples and reference pressure transducer are introduced into the chamber via the validation port. Then, the port and doors are sealed properly. There is a cycle, named as “Vacuum air test” cycle for leak test which is programmed in the PLC of the machine.
[][]During leak test, chamber pressure is reduced to a 70 mbar pressure and then this pressure is compensated and hold for 5 and 10 minutes respectively. The test is declared passed if the pressure rise is within 13 mbar within the holding time.
[][]If there is any leakage of steam for disintegration of gasket or any other reason, the autoclave might fail to achieve vacuum and leak test will be failed.
The results of above test will be recorded in the Appendix – 03 and will be accepted if met the acceptance criteria.

Bowie-Dick (BD) test:

[][]The Bowie-Dick (BD) test is done to detect air pockets and to evaluate that the vacuum retains as well as steam penetrates sufficiently for sterilization. This is because, air removal from the pores of the loads is essential for proper sterilization and to remove this air pre-vacuum pulse is important.
[][]For conducting this test, Bowie-Dick test paper kits will be exposed for 10 minutes at a temperature of 121.1OC inside the chamber. If the color of the centered sheet turns completely into black, it ensures proper vacuum of the chamber as well as proper steam penetration into the load and the test will pass.
[][]Any intermediate color change of centered sheets except black (e. g. grey, brown or blue) indicates the presence of residual air in the chamber.
[][]So, the test will fail. It may occur due to the failure of retaining required vacuum of the chamber and the insufficient steam penetration.
[][] In that case, increase the pre-vacuum pulse number or sterilization time which will ensure proper removal of air as well as the steam penetration respectively. This must be recorded in the report.
[][]The successful bowie-dick test’s pre-vacuum pulse numbers and sterilization time must be followed in the porous loads’ cycle.
The results of above test should be recorded in the Appendix – 04 and will be accepted if met the acceptance criteria.

Heat Penetration (HP) Study:

[][]The equipment must be run three times at fully loaded condition for each load pattern where twelve sensors are exposed to monitor the temperature within the loads as well as in the chamber.
[][]Care must be taken to avoid contact between the thermocouples and the metal surface of the chamber.
[][]Evenly distribute the thermocouples as it is shown in the Appendix – 2. In case of liquid load place the thermocouple no. 02, 03, 07 inside the container of the liquid.
[][]The Results of this test will be recorded in the Appendix-05 (Number of this appendix will be increased as per number of cycles) and will be accepted if met the acceptance criteria.

Microbiological Challenge (MC) test:

[][]This test will be performed with HP study. The temperature probes are distributed at different positions within the chamber and loads as per specified load pattern. Biological Indicators are placed beside the thermocouples as per BI placement diagram (Appendix – 01).
[][]It is to be noted that the Microbiological challenge test will be conducted for the heat penetration study cycles. Furthermore, the lethality value (F0) must be calculated by the TQ software and minimum lethality value must be recorded in Appendix 06.
[][]The results of above test should be recorded in the designated form (Appendix – 06). (Number of this Appendix will be increased as per number of cycles).

Acceptance Criteria

Chamber Leak test:

=>This test is deemed to be passed if the pressure rise of the chamber is within 13 mbar.

For Bowie-Dick test:

=>This test is passed if the color of the Bowie-Dick test kit turned uniformly to black having no intermediate color change throughout the entire pattern (e.g. gray, blue or violet) which ensures full vacuum and complete steam penetration.

For Heat Penetration (HP) study:

=>Throughout the sterilization period; all temperatures measured in the chamber has to be within a 4°C band from the set point i.e. 121°C (–1°C/+3°C).
During sterilization period; the difference in temperature between the coolest spot and the mean chamber temperature during sterilization hold period shall be within ±2°C.

For Biological Indicator Test:

=>Biological indicators must have an initial viable spore count of 106 or greater of the selected microorganism.
=>Biological Indicator must not show any growth after autoclaving and subsequent incubation.
=>Positive control biological indicators must show “growth” of Geobacillus Stearothermophilus.
=>The lethality (F0 value) must be equal or greater than 12 minutes.

Deviation And Failure Investigation Summary

In the column below, record any deviations or failures that occurred during the PQ exercise.

Deviation/ Failure No.Description and Assessment of Impact on ValidationInitialDate
1
2
3

Reference Documents

[][]SOP for validation of Moist Heat Sterilizer by Biological Indicator.
[][]USP general chapter <1222> Terminal Sterilized Pharmaceutical Products-Parametric release
[][]FDA Guidance for Industry ( for the Submission Documentation for Sterilization Process Validation in Applications for Human and Veterinary Drug Products); November 1994
[][]Practical Guide to Autoclave Validation by Raymond G. Lewis.

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Autoclave Performance Qualification Protocol

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Pest Control Procedure

Pest Control Procedure, Purpose

Pest Control Procedure, To prevent/control the entrance of pest & rodents within the facilities.

Pest Control Procedure, Scope

This SOP is applicable to control the entrance of rodents and insects both in-door and outdoor of the Plant of XX Pharma Limited.

Definition & Abbreviation

[][]Pest: Insects or animals that destroy plants, food & materials.
[][]Pest Control: Destruction of pest by appling poisons, traps or controlling of insets harmful for food, medicine, plants or packaging materials.

Responsibility

[][]‘YY Pest Control Company ’ is responsible to carry out the pest control activities on previously defined contact basis as per agreed valid schedule.
[][]Production & Quality Assurance  personnel are responsible to monitor that all insecticides are used in proper valid concentration & in all areas/points as described in the approved layout.
[][]Head of Quality Assurance & Head of Production shall ensure the implementation of this SOP according to GMP Guidance to ensure the safety of personnel, materials & products.
[][]Head of Administration or his nominee is mainly responsible to confirm that all Pest Control activities has been carried out in accordance with the predefined schedule.

Materials & Equipment

[][]Actellic 50ec
[][]Hydramethylnon
[][]Icon 10wp
[][]Icon 2.5ec
[][]Permakill concentate (Fogging)
[][]Phenol (C6H50H)
[][]Silosan
[][]Tespi liquid (Fogging)

Precaution

[][]Confirm that all raw material, finished goods, intermediates or any type of process goods should not be present in area of fumigation, if present cover all the materials with polythene bag.
[][]Perform all pest control activities only on weekly holiday/any Govt. Holiday when the Plant production activities are completely closed.
[][]Do not spray any insecticide inside the factory. Use only in outside of the factory.
[][]Before spraying/fogging confirm that all doors and windows of the factory are properly closed.
[][]Do not smoke/drink /eat during handling of any type of pesticides, do not breathe mists or dust, avoid prolonged contact with the skin.
[][]Always read the Material Safety Data Sheet (MSDS) for safe use and handling precautions given on the label.
[][] In the very beginning of office hour, Remove feeding traps from all application points.
[][]Always use goggles & nose-mask while doing fumigation.
[][]AHU shall be  switched off before starting fumigation.

Procedure

[][]Pest control operation shall be performed by the selected approved contractor (External: XX PEST CONTROL).
[][]The contractor shall provide the chemicals & plates of glue/gum & trap/baiting for trapping rats and mice.
[][]Admin Department shall prepare schedule with contractor & notify the date to Quality Assurance & other concerned department at least one week before initiating the program.
[][]Concerned department shall take necessary steps for covering related materials which are suspected to expose during pest control activities.
[][]Permanent precaution shall be taken so that no rats,  cockroach or insects can enter factory.

Schedule For Pest Control

Area
(Pharma Building)
Service
(Pest Control By)
Frequency
CorridorSpray1 time per month
Utility AreaULV2 times per month
Outside BuildingRat2 times per month
Canteen DormitoryFogging (Outside)2 times per month
Extra AreaSnakes1 time per month

Materials use for pest control

Ustaad (Sray & ULV)

[][]Active ingredient: cypermethrin
[][]Target pests: Mosquito, ants, cockroach, housefly,  bugs & ticks
[][]Dose & use strategy: 50-100ml/10 liter water

Dursban 20ec (for sray & ULV)

[][]Active ingredient: chloropyrifos
[][]Target pests: Cockroach, ants,  housefly, mosquito, bugs & termites
[][]Dose & use strategy: 50-100ml/10 liter water

Actara (for sray & ULV)

[][]Active ingredient: thiamethoxam
[][]Target pests: all types of termites,  ants,  white flies
[][]Dose & use strategy: 2-8g/10 liter water

Icon 2.5 EC (indoor/outdoor space spray & fogging)

[][]Active ingredient: lambda-cyhalothrin
[][]Target pests: pest adult
[][]Dose & use strategy:
[][]Hand held thermal fogging kerosene: mix 20-70 ml of icon 2.5ec in 1 liter of diesel or kerosene & apply fog.
[][]Fogging: mix 70 ml of icon 2.5 ec in 1liter of diesel or kerosene & apply fog in 2 ha space.
[][]Space spraying (water solvent) : mix 50-100 ml of icon 2.5 ec in 10 liter of water & spray

Permakill( for fogging)

[][]Active ingredient: permethrin
[][]Target pests: mosquitoes, flies, cockroach flying insects
[][]Dose & use strategy: 50-70 ml/1 liter diesel or kerosene for fogging.

Tepsi liquid (for fogging)

[][]Active ingredient: permethrin
[][]Active ingredient: Tetramethrin, Permetrin,Tralletrin
[][]Target pests: ants, cockroach, housefly, mosquito, bugs & ticks
[][]Use strategy: 50-500ml/10 ltr water for spray
[][]4:1 with diesel for fogging
[][]Materials use for use rodent only

Lanirat

[][]Active ingredient : 50 mg bromadeolon per kg-3-[3-(4-bromo[1,1-byfinail]-4il)-3hydroxy-1-finailprofile]-4-hydroxy-2h-1benzofiran-2-one)
[][]Target: rodent

Altorarat

[][]Active ingredient : non poisonous glue
[][]Target : rodent

Materials use snakes control

[][]Trapping is effective to control snakes. However rodent control is performed regularly, snakes control will be reduced. Following steps will be followed for snakes control:
[][]Use Phenol
[][]Use black hole trap
[][]Use snakes tongue for capture snakes safety

Annexure

Appendix –I: log book for pest control
Appendix –II: log book for cleaning after pest control

Pest Control Procedure Read More »

Functions of Quality Assurance

Functions of Quality Assurance, Purpose:

Functions of Quality Assurance, The purpose of this SOP ( Standard Operating Procedure) is to outline the functions, principle duties and responsibilities of personnel working in Quality Assurance Department.

Functions of Quality Assurance, Scope:

To provide the guidelines for the proper implementation of the Quality Assurance System at XX Pharmaceuticals Limited ( Both General and Cephalosporin Block).

Definitions / Abbreviation:

[][]Quality Control Department : The Department carrying out day to day activities for the control of procedure, tests & analysis of products/ raw materials/ packaging materials/ stability samples and other relevant analysis of samples at laboratory to assist the manufacturing functions.
[][]Quality Assurance Department: The department carrying out day to day activities for the control of procedure, analysis of documents, regulatory functions, to assist the plant functions for the manufacturing, distributions and other relevant functions.
[][]CAPA : Corrective Action and Preventive Action.

Responsibilities:

[][]The roles and responsibility is as follows:

Executive, Quality Assurance

[][]To follow the guidelines of Quality Assurance
[][]To report their findings to their seniors

Asst. Manager, Quality Assurance

[][]To ensure implementation of the SOP.

AGM, Quality Assurance

[][]Approval of the SOP.

Procedure:

[][]Quality Assurance Department shall function for assuring the quality of all the manufactured batches and every stage of manufacturing / processing of drug Products.
[][]This shall be achieved by performing the functions of monitoring as per the laid down QA systems for the following areas:
[][]Monitor of incoming starting and packaging materials.
[][]Manufacturing process and process checks.
[][]Process monitoring and process control.
[][]Production Record Review.
[][]Final release or rejection of every batch of Drug Products for distribution and sale.
[][]Monitor stability testing and evaluation of shelf-life of products.
[][]Complaints handling and product recalls.
[][]Handling of Change Control Systems.
[][]Out of specification investigation.
[][]Investigation of Deviations.
[][]Returned products ( salvage and disposal ).
[][]Internal Quality Audits.
[][]Co-ordinate monthly Quality Review Meeting and implement the effective CAPAs regarding quality improvement.
[][]Control of non-confirming products.
[][]Co-ordinate all validation and qualification activities.
[][]Reprocessing of non-confirming products.
[][]To achieve the objectives of Quality Assurance functions of XX Pharmaceuticals Limited is classified as follows :
[][]To plan and manage all the activities of Quality Assurance Department to assure the quality of all products manufactured by the Company.
[][]To co-ordinate with manufacturing department in controlling their process and products at every stage of manufacturing to meet the established specifications though testing, auditing and reporting.
[][]To co-ordinate for the development of new product formulation, development of specifications, analytical procedure in co-ordination with Quality Control Department and Product Development Department.

[][]To review the adequacy and relevance of specifications & analytical procedures in co-ordination with Quality Control Department and Product Development Department.
[][]To co-ordinate technical audits of the Quality Control Laboratory to determine the analytical quality systems are yielding the highest quality information and to ensure that the analytical instrumentation is functioning properly and calibration and servicing is as per schedule.
[][]To be responsible for the release functions of the QA Department which shall include :
[][]Maintenance of Quality Control records of manufacturing procedures for each manufactured batch.
[][]Records of release, quarantine or rejection of components and finished products, containers, closures and labels based on Quality Control test results.

[][]Routine “Good Manufacturing Practices Auditing” of manufacturing process, control and related areas.
[][]To suggest and organize training program for the development of technical and administration skills of all the employees to meet with cGMP regulations on continuous basis, coordinating with GM, Plant and Quality Head.
[][]To assist Change Control Committee/Technical Committee for overall reviews of non-conformances, failure investigations, analyzing the Quality trends, investigations of market complaints, batch failure investigations, deviations, verifications of change control procedures, updating the specifications, test procedures, manufacturing processes etc.
[][]To liaison with regulatory authorities for new products manufacturing license and renewals of the same and other regulatory requirement.

Annexure:

N/A

Functions of Quality Assurance Read More »

Contract Manufacturing by Third Party

Contract Manufacturing, Purpose:

Contract Manufacturing, To establish a procedure that XX products are manufactured by the contractor using facilities and operations and to ensure that all batches of product manufactured at third party contract manufacturer that conforms to cGMP requirements undergo a formal evaluation of suitability for use prior to release to the market.

Contract Manufacturing, Scope:

The SOP is applicable for all products of XX Pharmaceuticals Limited manufactured & packed by a third party contract manufacturer.

Definitions / Abbreviation:

[][]QA – Quality Assurance
[][]QC – Quality Control
[][]QA – Quality Assurance
[][]BMR – Batch Manufacturing Record
[][]BPR – Batch Packaging Record
[][]ERP – Enterprise resource planning.
[][]cGMP – Current Good Manufacturing Practice
[][]COA – Certificate of Analysis

Responsibilities:

[][]The roles and responsibility is as follows:

Third party contractor

[][]To perform all the manufacturing related activities, analysis of the manufactured & packed product as per the contract/ toll manufacturing agreement

Executive, Production

[][]To check and review the production related activities.

Executive, Warehouse

[][]To supply and update the required raw and packaging materials as per forecast

Executive, QA

[][]To verify the overall manufacturing activities, collection of sample and related documents

General Manager, Plant

[][]Proper follow-up of overall activities

Manager, Quality Assurance

[][]Approval of all the toll manufacturing activities.

Procedure:

Selection of Third Party/ Contract Manufacturer

[][]Carry out GMP audit to assess the prospective contractor’s technical capability, capacity, cost effectiveness & the capability to maintain the required standards of cGMP & product quality.
[][]Document the business objectives and the justification for selecting a third party contractor.
[][]Review the manufacturing strategy which will be applied to the third party contractors.
[][]After developing a third party contract manufacturer, provide the product and their volume to the third party contractor for its technical assessment of manufacturing capability.
[][]Multiple strategies to be followed in selecting third party contractor.
[][]Consider the sources of materials which must meet the approved specification.
[][]Sign a contract manufacturing agreement with the selected contractor for manufacturing / packaging of products which will be followed accordingly.

[][]XX personnel will generate all the relevant documents as per contract manufacturer’s requirements for batch production.
[][]Production Executive will supply a production forecast of the required quantities of each product two months in advance so as to consider in third party’s

[][]production plan. XX shall have the right to revise the forecast in accordance with the market situation informing contractors one and half month in advance.
[][]Warehouse personnel of contract manufacturer will generate a month wise stock statement for raw and packaging materials to XX.
[][]Production Executive will generate the batch no. as per production forecast to Quality Assurance Executive along with requisition copy for BMR & BPR.

[][] QA Executive will issue the photocopy of BMR & BPR to Production Executive for manufacturing by third party. Master copy of all documents will be preserved at QA end.

[][]For testing procedure of raw and packaging materials will be followed as per contract manufacturing agreement. If any material (Raw/ Packaging) which will be tested by third party, will be forwarded by QC Executive from QUARANTINED stage along with forwarding letter to the contractor.
[][]After receiving the test report from third party, QC personnel will disposition the materials as PASSED/ REJECTED following the SOP.
[][]Production Executive along with warehouse Executive will supply all the materials to third party following the production forecast as per requirement within first week of running month. During supply of materials warehouse executive to be ensured the status label as per requirement by third party.
[][]Contract manufacturer will follow their production schedule and manufacturing operation will be started at the presence of Production and QA personnel of XX.

[][]XX personnel will verify all the written instruction in the BMR & BPR following the third party’s SOP as per cGMP requirement.
[][]All the in-process checks (IPC) will be conducted by contract manufacturer along with XX personnel.
[][]In case of any process validation activities will be conducted by XX personnel using the facility of third party.
[][]For testing of bulk intermediate and finished product, responsibility will be performed by XX and contract manufacturer as per contract manufacturing agreement.
[][]Sample for in-process check, chemical test and microbial test will be withdrawn as per agreement policy following the SOP of XX or contract manufacturer. [][]Finished product samples will be withdrawn as per same requirement.
[][]Retention sample will be kept at contract manufacturer’s end. If the retention sample is required for XX, then the sample will be forwarded to XX end by contract manufacturer following their own policy.
[][]Stability sample will be withdrawn from packaging line as per stability protocol and to be forwarded by contract manufacturer to XX end.

[][]If the stability test will be performed by contract manufacturer, samples will be kept in the manufacturer’s end as per protocol. In that cases test report will be forwarded to XX end accordingly. After receiving all the stability data, QA Executive will prepare the stability report.
[][]Third party contract manufacturer’s site will provide XX personnel with full batch documentation, copies of any unplanned event or deviation (including OOS), a copy of any investigation reports and COA reporting analytical test results against specification.
[][]QA and production personnel will review all the batch documents along with supportive records as per checklist for batch documentation after prior release from contract manufacturer.
[][]Original batch document or photocopy of the original will be provided by the contract manufacturer to XX end.

[][]Production personnel will issue the used quantity of raw and packaging materials in the ERP software with the help of IT personnel according to batch production record to update the material status.
[][]After reviewing the batch document, Production and QA representative will send the notification to the third party contract manufacturer about the batch disposition decision.
[][]Upon receiving the batch disposition decision from XX Pharmaceuticals Limited, the third party contract manufacturer will take step accordingly.
[][]XX shall take delivery of the finished products in XX’s own liabilities within fifteen days of intimation by contract manufacturer that the product is ready for dispatch.

[][]After completion of cost related process by both XX and contract manufacturer, central warehouse will receive the finished product and kept in the central warehouse of XX as per storage condition.

Annexure:

None

Contract Manufacturing by Third Party Read More »

Finished Product Handling, Storage & Distribution

Finished Product Handling, Purpose:

Finished Product Handling, The of these guidelines is to assist in ensuring the quality and identity of pharmaceutical products during all aspects of the distribution process such as storage, distribution, transportation, packaging, labeling, documentation and record-keeping practices.

Finished Product Handling, Scope:

This procedure is applicable for all finished products received and stored after receiving from Packaging department by Central Warehouse and different depots of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]QA – Quality Assurance
[][]DIC – Depot In Charge
[][]ERP – Enterprise Resource Planning
[][]CWH – Central Ware House
[][]FIFO – First In First Out
[][]XX – Current version no. of the SOP

Responsibilities:

[][]The roles and responsibility is as follows:

Head of Distribution

[][]Head of Distribution shall responsible for overall the distribution activities.

Depot In Charge (DIC), Central Warehouse & Different Depots

[][]To verify, receive, storage and distribution the finished goods ensuring all the quality.

Head of Sales

[][]To monitor the distribution procedure as per market requirement.

Head of Marketing

[][]Prepare the market requirement for distribution and follow-up of overall activities.

General Manager, Plant

[][]Follow-up of overall activities.

Executive, Vat

[][]Follow the distribution activities as per Government legislation

Executive, QA

[][]Responsible for effective implementation and monitoring of procedure.
[][]Annual depot audit to verify the effectiveness of this procedure.

Manager, HR & Admin

[][]Shall responsible for monitor the effective distribution procedure

Manager, Quality Assurance

[][]To approve of all the distribution activities.

Procedure :

Precautions:

[][]The entire finished product should be handle carefully during distribution, storage, ensuring the quality and identity of the product.
[][]The entire finished product should be stored in product wise respective area maintaining product’s storage condition.
[][]During distribution FIFO should be controlled to avoid mix-up & errors.

Storage :

[][]Finished product will be received by central warehouse personnel from packaging department after getting the finished product release note from QA.
[][]Released finished product will be stored in the central warehouse at the product wise respective area as per storage condition.
[][]Warehouse personnel will monitor and record the temperature in “temperature monitoring record sheet ( Annexure – I)” for twice in a day.
[][]Storage areas should be designed or adapted to ensure appropriate and good storage conditions.
[][]In particular, they should be clean and dry and maintained within acceptable temperature limits. Products should be stored in the pallet which is suitably spaced to permit cleaning and inspection.
[][]Physical or other equivalent segregation should be provided for the storage of released, rejected, expired, recalled or returned products and suspected counterfeits.
[][]Broken or damaged items should be withdrawn from usable stock and stored separately up to final disposition.
[][]Storage areas should be provided with adequate lighting to enable all operations to be carried out accurately and safely.
[][]Periodic stock reconciliation should be performed by comparing the actual and recorded stocks. Stock discrepancies should be investigated by a multidisciplinary committee headed by HR & Admin.

Distribution

[][]All parties involved in the distribution of pharmaceutical products have a responsibility to ensure that the quality of pharmaceutical products and the integrity of the distribution chain are maintained throughout the distribution process from the site of the manufacturer to the entity responsible for dispensing or providing the product to the target consumer as per Government legislation.
[][]Head of Distribution send the depot wise market allocation to central ware house as per marketing/sales requirement.
[][]Central warehouse personal will prepare the released finished product as per market allocation for different depots along with necessary tertiary packaging.
[][]In-charge, CWH will prepare invoice/challan copy as well as ERP entry as per different depot requirement approved by head of Plant or his designee.
Executive, Vat will prepare the vat challan according to depot allocation ( through Musak-11) as per Government rule.
[][]After performing all the related activities, finished products will be transferred to different depot by company own transport or transport agent along with vat challan and invoice copy.
[][]DIC or designee will receive and check the finished pack according to invoice and to be stored following the procedure described on previous steps.

Market Dispatch :

[][]DIC will allocate the finished product as per market requirement for sale. The dispatch and transportation of products should be undertaken only after the receipt of a valid delivery order, which should be documented
[][]Dispatch record will be prepared by DIC and should include at least the following information:
[][]Date of dispatch;
=>Complete business name and address (no acronyms), type of entity responsible for the transportation, telephone number and names of contact persons;
=>Complete business name, address ( no acronyms), and status of the addressee (e.g. retail pharmacy, hospital or clinic);
=>A description of the products including, e.g. name, dosage form and strength ( if applicable);
=>Quantity of the products, e.g. number of containers and quantity per container ( if applicable);
=>Applicable transport and storage conditions;
=>A unique number to allow identification of the delivery order; and
=>Assigned batch number and expiry date ( where not possible at dispatch, this information should at least be kept at receipt to facilitate traceability).

Returned :

[][]If any products undergo as expired or packet damaged which is not fit for use then record the product and stored in a separate area of the depot/warehouse with proper labeling following annexure– II under custody of depot in-charge.
[][]DIC will make an invoice of those products and sent to central warehouse after entry in the ERP to adjust the stock. Returned products will be sent to CWH at every three months interval.
[][]Head of distribution will collect this invoice/challan from different depots and sent to central warehouse after getting prior approval from Head of Sales & Head of Marketing.

[][]After receiving the returned products from different depots, in-charge, CWH will report to QA department along with the approved invoice/challan copy. In-charge, CWH will segregate the returned products according to their nature in a separate area with proper labeling as per annexure-II.
[][]QA executive will take actions following the SOP ‘Disposition of Returned Finished Products.
[][]In case of market compliant or product recall, DIC will inform to Sales or Marketing Department following the respective SOPs Head of distribution will collect the market compliant sample (s) or recalled product(s), batch(s) within seven days of initiation.
[][]Head of QA will take actions for the market compliant and product recall procedure following SOP.
[][]Stock verification of different depots will make through a physical audit by the representatives of Audit & Accounts department once in a year.
[][]A quality audit will be conducted for all the depots headed by QA representative once in a year.

Annexure:

Annexure I – Temperature monitoring record sheet
Annexure II – Returned product label

Finished Product Handling, Storage & Distribution Read More »

Returned Finished Products Disposition

Returned Finished Products Disposition, Purpose :

Returned Finished Products Disposition, The objective is to specify a system to handle the returned finished products for their appropriate and adequate review and disposition in line with the Quality Management System.

Returned Finished Products Disposition, Scope :

This procedure is applicable for disposition of returned finished products and expired ones at XX Pharmaceuticals Limited. (Both General & Cephalosporin Block).

Definitions / Abbreviation:

[][]QA : Quality Assurance
[][]DIC : Depot In Charge
[][]XX : Current Version of SOP

Responsibilities:

[][]The roles and responsibility is as follows:

Head of Distribution

[][]Head of distribution shall collect the finished products from different depots and forward to the central warehouse for final disposition as per procedure.

Depot In Charge (DIC), Central Warehouse

[][]To verify, receive and separately quarantine the returned goods.

Executive, QA

[][]Responsible for effective implementation and monitoring of procedure.

Senior Executive, Cost & Budget (Factory)

[][]To verify all the returned products and make report for stock adjustment memo.

Head of Plant Operation

[][]Follow-up of overall activities.

Head of Quality Assurance

[][]Approval of all the disposition activities.

Procedure:

[][]The returned finished products shall either be destroyed or repacked and made fit for use depending upon the reason for which they have been returned. In either case, the associated risks must be well understood and addressed.
[][]Hence the procedure for disposition of returned finished products is defined depending upon the reason for which products are returned.
[][]Head of Distribution will collect the finished product as per requirement from different depots and send to Central warehouse following the Invoice/ Challan.
[][]On receipt of the products, warehouse (Central) In Charge or designee shall verify the products as per Invoice / Challan. Then warehouse in-charge will label the products to identify the primary cause of return and segregate the returned products in the respective area.
[][]Quarantine the products in area as per classification and inform QA and Head of Plant Operation through Returned Finished Product Note, (Annexure – I).
[][]Reference number for Returned finished products shall be alphanumeric system containing 7 characters. Numbering breakdown is as follows : RG/YY/001
For example : RG/XX/001
=>The first two alphabets shall stand for Returned Goods
=>Next two numeric characters shall stand for year code XX shall denote year 20XX.
=>Next character is followed by three numerical shall stand for serial number, which shall start every year
from 001.

[][]All the expired products returned from the market shall be directed and received at the distribution Department and these shall be destroyed in presence of QA Executive following the SOP of Procedure for Disposal of Materials & Products.
[][]QA Executive shall prepare Authorization and Disposal From for Materials & Products and take authorization for disposal activities.
[][]Head of Quality Assurance or designee shall arrange to verify the reason for return/ recall of the returned products against the intimation.
[][]If the returned products (except expired products) which are fit for further use they shall be repacked through repackaging request form following the Reprocessing/reworking and Repackaging Procedure.
[][]Quality Assurance personal shall examine the products returned because of dirty labeling, packed damaged products can be repacked. To ensure the product quality, QA executive shall draw the sufficient sample for complete analysis (If necessary) and only if found satisfactory and certified accordingly, then the batch shall be allowed for repacking.
[][]For the repackaging activities minimum five unit packs are required for the returned product of same batch no. Less than five unit pack of a same batch shall be disposed following the disposal SOP.
[][]The returned products except expired products which can be repacked to be sent from central warehouse to the manufacturing site and shall be classified and stored separately depending upon the primary cause of return.
[][]Record for issue of packaging material, overprinting and packing shall be maintained on Additional Batch Packaging Record (Primary/Secondary) along with the Repackaging Request Form authorization by Head of Quality Assurance.
[][]If the returned products in the opinion of the Quality Assurance personnel are not considered fit for repackaging, the same shall be destroyed after approval from Head of Quality Assurance.
[][]This repacked part shall be released after compiling of the all related documents and shall be attached to the earlier batch record (BMR/BPR)
Products recalled voluntarily or recalled, as per the directives from Drug Control Authorities the recalled products shall be handled depending upon the reason for product recall; they may be require to be destroyed or repacked.

Annexure:

Annexure I – Returned Finished Product Note

Returned Finished Products Disposition Read More »

Cleaning Validation Procedure

Cleaning Validation, Purpose:

Cleaning Validation, To lay down a procedure for carrying out cleaning validation to establish validated cleaning procedure for manufacturing and primary packaging equipment and effectively maintain cleaning process in validated state. Cleaning must be demonstrated to be effective in order to provide assurance that unacceptable levels of contamination are not carried over into subsequent products. It defines the cleaning validation and verification requirements to ensure that all cleaning procedures which may impact product quality are formally validated or verified. Cleaning must be demonstrated to be effective in order to provide assurance that unacceptable levels of contamination are not carried over into subsequent products. It defines the cleaning validation and verification requirements to ensure that all cleaning procedures which may impact product quality are formally validated or verified.

Cleaning Validation, Scope:

This procedure is applicable for equipment’s used in product manufacturing and primary packaging of XX Pharmaceuticals Limited (Both General & Cephalosporin Block).

Definitions / Abbreviation:

[][]QA : Quality Assurance
[][]QC : Quality Control
[][]CIP : Clean-in-place
[][]OOS : Out of Specification
[][]MACO : Maximum Allowable Carryover

Responsibilities:

[][]The roles and responsibility is as follows:

Concerned Department

[][]To cooperate the validation team to make the cleaning validation job successful.

Quality Assurance

[][]Responsible for the developing and co-ordinate the entire cleaning validation activities as a team leader.

Quality Control

[][]Ensure that analytical method has been prepared and validated before conducting cleaning validation and coordinate all analytical & Microbiological test.
To coordinate all the sampling activities.

Head of Plant Operation

[][]Proper follow-up of overall activities.

Head of Quality Assurance

[][]Approval of all the validation activities.

Procedure:

[][]Prior to conducting a cleaning validation study on an Active Ingredient (of previous product) following activities need to be summarized. A Validation team shall be formed comprising of members from Production, Engineering, Quality Control, Validation / Quality Assurance.

Defining the key elements

[][]Define solubility, toxicity of active ingredient in cleaning validation protocol. If any of the active ingredients are deemed to be more potent or less soluble in water than the ingredients for which cleaning validation has already been completed, or deemed to be particularly difficult to clean from equipment, a new validation study will be carried out.
[][]Define the product-equipment matrix.
[][]Prepare the equipment matrix. Determine the total contact surface area of the equipment/ instruments which are to be used in the manufacturing of that product with the help of Engineering and Production Department.
[][]Determine the scope and establish acceptance criteria.
[][]Develop and validate sampling procedure and analytical method.
[][]Designing the cleaning validation protocol. All protocols shall be as per the Format given I Annexure- I.
[][]Execute the cleaning validation study and protocol.
[][]Summarize the data and compilation of the final report.
[][]Devising and monitoring program to establish that the cleaning process is continued to be in validated state.
[][]Establishing conditions for which re-validation would be required.

Describing the key elements

[][]The product – equipment matrix
[][]Prepare a Product–equipment matrix (Annexure-II) & Equipment matrix (Annexure-III) for the products, equipments used in the cleaning validation study.
[][]The matrixes will provide information about the manufacturing and packing line used for multiple products and possible product contact surface area.
[][]The matrix will indicate the worst case at a glance and justify the acceptance criteria for a cleaning validation.

Determining the scope

[][]The scope includes evaluation of residual contamination of active ingredient.
[][]Cleaning validation to be done based on matrix for including any new product in to the matrix for supplying product to local market. However, all products deemed to be supplied to highly regulated markets, the cleaning validation to be done for every product.
[][]Acceptance criteria for Residual active ingredients: The approach for setting limits can be (1) product specific cleaning validation for all products; (2) grouping into product families and choosing a worst case product; (3) grouping into groups of risk (e.g. cleaning difficulty, solubility, toxicity potency of API, facility volume of product); (4) setting limits on not allowing more than a certain fraction of carryover; (5) different safety factors for different dosage forms.
[][]For determining cleaning validation process, widely used criteria, i.e. 1/1000, will be consider for MACO calculation and to evaluate the cleaning effectiveness.
Establish the limit for Maximum Allowable Carryover (MACO) according to the following equation.

MACO = TDD Previous X MBS/ SF X TDD Next

Where,
=>MACO = Maximum Allowable Carryover: acceptable transferred amount from the investigated product ( “previous” )
=>TDD Previous = Standard therapeutic dose of the investigated product ( in the same dosage form as TDD next)
=>TDD Next = Standard therapeutic dose of the daily dose for the next product.
=>MBS = Minimum Batch Size for the next product(s) (where MACO can end up)
=>SF = Safety Factor ( normally 1000 is used in calculation based on TDD )
#(Ref. APIC : Active Pharmaceutical Ingredients Committee)

[][]However, the other criteria i.e. 10 ppm Criteria, API toxicity data will also be taken into consideration for evaluation of cleaning effectiveness. The cleaned equipment’s will also be checked visually to ensure the cleaning effectiveness.
[][]1/1000 Criteria: NMT 0.1% of the normal therapeutic dose of any product to appear in the maximum daily dose of the following product.
[][]10 ppm Criteria : NMT 10 ppm of any product to appear in another product;
[][]Based on toxicity : LD50 Value of API will be considered;
[][]Visual Inspection: No quantity of residue to be visible on the equipment after cleaning procedures is performed.
[][]API Solubility: The solubility of drug in washing solvent plays a great role in cleaning. The lesser the solubility greater will be the difficulty to remove the residue from surface.
[][]Thus least soluble molecule (based on the pharmacopoeia or other reliable reference) will be taken for the analysis since if least soluble molecule gives satisfactory result in cleaning validation and routine monitoring then we can rest assure for the other higher soluble drug.
[][]API Toxicity: An evaluation according to the toxicities should be carried out based on the material safety data sheet (MSDS).
[][]Other risk factors such as potency and facility volume of a particular product should also be taken into consideration during designing cleaning validation program.
[][]Develop and validate analytical method for cleaning validation sample analysis.

Swab sampling

[][]Generally method involves swabbing of 5 cm2 but larger area could be considered as per regulatory dossier or with proper justification and difficult to clean areas will be considered as per below Diagrammatic representation.
[][]Define the most difficult to clean areas in the piece of equipment (show delineate pictorially as far as possible).
[][]A polyester tipped swab (Texwipe, Alpha swab with long handle) shall be used. One side of swab shall be given horizontal 10 strokes and then reverse side of the swab shall be given vertical 10 strokes.
[][]The swab stick shall be dipped into the screw cap test tubes/ vials containing solvent (Approximately 10 ml). One test tube / vial will be taken for each swab sample.
[][]The test tube / vial will be labeled specifying the particular piece of equipment swabbed & the location (where appropriate).
[][]The soaked swab (in solvent) to be firmly squeezed along the side of the test tubes / vials and then sampling side to be swabbed. After taking samples from the equipment/utensils the swab to be returned to the respective screw cap test tube/vial.

[][]Each vial will be closed with swab inside & sent to QC for analysis of the swab sample.
[][]Study and establish the stability of sample solution storage condition & storage time, based on a protocol.
[][]Perform the recovery analysis on the swab with spiked SS surface/ similar to the equipment material of construction. Recovery of drug shall be not less than 85% after taking into account interference of swabbing material.
[][]Perform the recovery study of the API from the swab stick for record only.
[][]Mention the swab sampling point details in the cleaning validation protocol.

Rinse sampling

[][]For rinse sample collection graduated plastic mug/container, plastic squeezer, stainless steel container to be used, will be cleaned first with 70% IPA followed by sufficient purified water (Wipe with lint free cloth soaked in 70% IPA if required after visual inspection).
[][] After collection of each rinse the required quantity will be transferred to the conical flask for QC submission. To discard the leftover residue in the SS container/ plastic mug these utensils will be cleaned with sufficient purified water before next use.
[][]Same procedure will be followed for MDI unit except for cleaning purpose only absolute ethanol will be used instead of 70% IPA and purified water.
[][]Rinse sample can be evaluated at intervals during the cleaning and at the completion of the cleaning process. Collection of rinse samples should consider location, timing and volume.
[][]Rinse sample allow sampling of a large surface area and of inaccessible systems or ones that cannot be routinely disassembled. However consideration should be given to the fact that the residue or contaminant may be insoluble or may be physically occluded in the equipment.
[][]Study and establish the stability of sample storage conditions and storage time, based on a protocol.
[][]For those equipment or parts (e.g. turret, die and punch of compression machine, hopper) rinse sampling method is not feasible, only swab sampling method will be applied.
[][]At first swab sample will be collected as per plan and will be sent to QC. Then the swab taken area will be cleaned with purified water and finally with lint free cloth.
[][]At first the equipment will be cleaned as per the equipment cleaning SOP and the dismantled parts will be stored in the clean equipment store room after drying.
[][]After collecting rinse samples the cleaned equipment’s will be allowed for self drying before next use. Finally the rinse sample in a closed conical flask with proper labeling will be sent to QC for analysis.

[][]Perform the recovery analysis on the rinse with spiked SS surface/ similar to the equipment material of construction. Recovery of drug shall be not less than 85%.
[][]Microbiological considerations: weather or not CIP systems are used for cleaning of processing equipment, consider the microbiological aspects of equipment cleaning.
[][]The equipment/utensils are considered clean if the total microbial count is less then 25 CFU per 25 cm2/ per swab or 100 cfu/ml taken from equipment/utensils surface and there are no objectionable organisms present ( e.g. E.coli, Salmonella, Pseudomonas aeruginosa, Staphylococcus aureus).

[][]If any growth is observed, appropriate tests to identify the organisms are to be conducted. If the acceptance limit is exceeded, or an objectionable microorganism is identified, then then an OOS investigation must be initiated by the Microbiological Laboratory to identify the source of microbial contamination. Investigation should be done by the manufacturing department.

[][]Contaminated equipment must be re-cleaned and re-swabbed/re-rinsed and it be must meet acceptance limits prior to release for further manufacturing.
For all the types of equipment initial cleaning validation shall be performed on at least three consecutive batches or three runs.

Bracket Approach

[][]The design uses the extremes to cover in between range. That is the largest pieces of identical equipment could cover all of the in between sizes.
[][]The lowest and highest strength of the products.

Worst Case Approach

[][]The most difficult to clean equipment could cover all the easier to clean equipment also.

[][]Initially cover all the types of equipment for three runs.
[][]Type A cleaning done after 6 days (144 hours) from the first day of use of the equipment or area of solid dosage forms.
[][]The dirty holding period of manufacturing equipment should not be more than 5 days.
[][]In case of batch size change, either increase or reduction in the batch size, the matrix shall be re-evaluated.
[][]If a drug product is manufactured in different strengths, cleaning procedures shall be validated for the highest strength of that particular drug product. If the manufacturing line contains multiple products or a single product contains multiple active ingredients, the active ingredient which is least soluble/more in concentration and/or more toxic, hard to clean shall be taken into consideration for cleaning validation/verification.
[][]If there are multiples of particular equipment with same configuration, material of construction and cleaning procedure then cleaning validation of one piece of that particular equipment will be adequate.
[][]If there are different sizes of the same equipment with same cleaning procedure, cleaning validation for the largest size of that particular equipment is adequate.
[][]The worst case selection criteria will be a) Hard to clean product (Color and Flavor) b) Least soluble API c) Maximum toxicity of API d) Minimum therapeutic daily dose e) Facility volume of a particular product.

Execution of cleaning validation protocol/study

[][]Adequate training to the operators (Production, QC and Engineering) shall be given and documented to execute the protocol efficiency.
[][]Ensure that during validation study the results and activities represent regular daily operations.
[][]Ensure that the same piece of equipment is available for the execution of the cleaning by the operators.
[][]Ensure that operator’s variability is addressed during the process design to maximize the representation of results.

=>Cleaning Validation Protocol number shall be given as follow;
CVR/XXX/YY
Where
=>CVP stands for Cleaning Validation Protocol/stands for separator
=>XXX stands for the sequential number which starts from 001 for calendar year.
=>YY stands for the last two digit of the year.

Summarize the data and generate the report

[][]The final result of particular sampling site shall be ‘difficult to clean’ reported and incorporated in the calculations.
[][]Test results shall be complied by Validation/QA.
[][]Any change in procedure shall be approved by QA.
[][]Evaluation of product matrix shall be done periodically or during introduction of any new product into the existing facility.
[][]Objective & Scope: Describe the objective and scope of the cleaning validation / verification in cleaning validation /verification protocol.
[][]Cleaning Validation/Verification Protocol: provides the tabulated test results and the acceptance criteria for each piece of equipment and equipment train.
[][]Cleaning Validation/Verification process shall be concluded with a summarized report incorporated as a final report, which is written and approved.
[][]Tabulation of test results: provides the tabulated test results and mention the acceptance criteria for each piece of equipment and equipment train.
[][]Discussion and Conclusion: discuss the cleaning validation program under study and summarize the outcome of the cleaning validation program.
[][]Cleaning Validation Report number will be same as protocol no. given as follows.
=>CVR/XXX/YY
=>Where, CVR stands for Cleaning Validation Report.
=>Revalidation of cleaning procedure is required in case of following change
=>Equipment or equipment configuration changes.
=>Changes in cleaning procedure and change of formulation where active quality is increased (e.g. overage).
=>Change in acceptance criteria due to change in batch size or introduction of new product (the matrix shall be Re-evaluated by preparing a separate cleaning validation protocol).
=>Process change in manufacturing process (e.g. wet granulation to direct compression and vice versa).
=>The significance of change shall be evaluated collectively by Production, Engineering and QA.
=>Whenever any change control is made to a validated cleaning procedure, due to change in equipment, process, repair or any other valid reason, then the need evaluation shall be done jointly by the Head of Production, Head of Engineering and finally approved by Manager QA.
=> If the decision is made to revalidate, the same be implemented.

Annexure:

Annexure I-Cleaning Validation Protocol
Annexure II-Product Equipment Matrix
Annexure III-Equipment Matrix

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Product Quality Review

Product Quality Review, Purpose :

Product Quality Review, The objective of carrying out Product Quality Review (APR) is to establish that the product is manufactured as per approved procedures and the trends of results of critical quality attributes are well within acceptable limits.

PQR will also address the review of raw & primary packaging materials used, process validation & revalidation, analytical method validation, cleaning validation & revalidation, stability testing reports, yields, change controls, out of specification results, deviations, failure investigations, CAPAs, rework & reprocessing, market complaints report, trend analysis data, vendor addition/deletion, supplier performance review, retention sample review, batch documentation, drug authority (legal) notices, equipment/utility required, environmental monitoring, etc. done during the review period.

Scope :

[][]This procedure applies to all product manufactured XX Pharmaceuticals Limited (both General & Sterile Block) and is carried out for products manufactured for during calendar year e.g., January to December.

Definition/Abbreviation:

[][]SOP : Standard Operating Procedure
[][]CAPA : Corrective and Preventive Action
[][]PQR : Product Quality Review

Responsibilities:

[][]The roles and responsibility is as follows:

Executive, QA

[][]Responsible to carry out the periodic review of particular product and prepare a report.

Asst. Manager, QA

[][]Responsible to ensure that a formal review of Drug Product / API is undertaken and reported periodically and demonstrate control of the process and effectiveness of any corrective actions required.

Head of Concern Department

[][]To ensure implementation of suggested CAPA.

Head of Quality Assurance

[][]Approval the SOP

Procedure:

Selection of batches

[][]Select the all batches of a product manufactured in the review period.
[][]The batches which are reworked / reprocessed are used must be included in product quality review.
[][]Frequency
[][]Product quality reviews of Drug Products shall be conducted and documented annually.

Schedules for Review

[][]A suitable schedule has to be drawn up by assigning products to person so that review of all products is completed for the stipulated period. The compilation data should preferably to be completed within one month after receiving all data of last batch of evaluation period.
[][]Review of Batch Manufacturing and Packing Records
[][]Review the batch production records for the following particulars:
[][]Review the batch production and packing records of all the batches selected for PQR and record the details like batch numbers, batch production record number and final yields etc.
[][]Review any batch rejections and reprocessing or reworking done during the review period. In such cases highlight the reason, and record the corrective action taken.
[][]Review the process deviation reports are duly adequately investigated, completed and approved.
[][]Record yields of all isolated stages of the product and the yield ranges for all the batches reviewed. Highlight reasons for out of specification yields if any as well as extremes, which are well within limits.
[][]Compile the yield data and prepare the trend charts. Analyze the trend charts, identify and investigate any discernible trends, which are within acceptable upper and lower specifications. Attach the trend charts as in graphical presentation a part of PQR report.
[][]Review in-process control data for key process steps carried out during the manufacture and highlight critical deficiencies.

Review of Environmental Condition

[][]Record the observation for Assurance with environmental condition of manufacturing areas. Critical deviation, if any must be examined in detail to assure how the deviations were taken care of and record observations.

Review of Analytical Reports

[][]For all the batches under product quality review verify all the analytical reports for the following:
[][]Validity of analytical specifications and methods for the products, raw materials and primary packaging materials employed.
[][]Any out of specification analysis and re-testing carried out with explanations for the same.
[][]Review the analytical results for critical parameters like assay, dissolution, loss on drying/water content, related substances etc.
[][]Review any specification changes and also any new analytical instruments added for the testing of the product and raw/primary packaging materials involved in manufacturing the batches for PQR.
[][]Review the calibration /qualification status of instruments used in the analysis of the batches under review.
[][]Review the retention samples randomly for deterioration.
[][]Compile all the critical analytical data (e.g. assay, dissolution) in a graphical presentation as a part of PQR.

Review of Stability Study Program and Data

[][]Stability review data generated for the product during the review period must be verified and critical observations, if any, highlighted with corrective action recommended. On need basis, the review should be extended to previous years as well.

[][]Any recommendations for changes in shelf life must be examined. Record any changes to stability testing protocol and methods during the review period. Any stability failure during the period must be reviewed in detail.

Review of Market Complaints, Returns and Recalls

[][]Market complaints received during the 12 months period of review should be verified for appropriate closure. The corrective & preventive actions taken subsequent to the complaint investigations should be reviewed in detail. Any recall during the period also must be reviewed in detail.

Review of Regulatory Actions

[][]Any regulatory queries with respect to the product under review must be examined in detail. The corrective actions taken and company response to the queries must be examined.

Review of Validation Status

[][]Any validation or revalidation exercises carried out for the process or equipment related to the product under review must be reviewed and findings to be highlighted. Corrective & preventive actions (CAPA) taken, if any, must also be reviewed. Analytical method validation and cleaning validation/revalidation performed during review period must be recorded.

Review of Change Control Documents

[][]Review all the changes made to the system related to the product under review and report the impact on the regulatory and or customer requirements.
[][]Review of Non-conformity and CAPAs
[][]Review the non-conformities and corrective & preventive actions (CAPA), if any, during the internal quality audits.

Review of Critical Equipment & Utility performance

[][]Performance of the critical equipment & utilities used for manufacturing, packaging & testing of the product during the period to be reviewed.

Review of Raw & Primary Packaging Materials

[][]All the batches/ lots of raw materials (active & excipients) and primary packaging materials used for manufacturing & packing of product during the review period to be reviewed.

Review of Vendor Addition/Deletion and Supplier Performance Report

[][]Vendor addition/deletion and supplier performance reports of raw materials (active & excipients) and primary packaging materials to be reviewed.

Review of Retain Sample

[][]Retain samples (retention samples) of all the batches of the finished products to be reviewed every year by visual examination for any evidence of deterioration and observation shall be documented in respective retention sample register. A summary report to be prepared based on the visual inspection. The same report will go to the PQR.

Review of previous APR Report

[][]Observations/recommendations of the previous Product Quality Review report to be reviewed.

Review of Environmental Monitoring:

[][]Annual review of environmental monitoring summary report to be reviewed and a copy of the summary to be affixed as an annexure with the PQR. Any result exceeds the action limit and the actions against the exceed results to be recorded in the review report.

Report:

[][]An overall summary of the annual product review report shall be prepared by the person conducting the review.

[][]Any other observations or improvements or recommendations for improvements if any shall be given in the report.
[][]The report should include trend charts for all relevant data supporting the review.
[][]The report should include a summary and recommendations for actions to be initiated for any deficiencies.
[][]Document Numbering:
[][]Annual Product Review report shall be numbered as follows:
=>PQR/XX/YYY
=>Where ‘PQR’ represents for Product Quality Review.
=>‘XX’ represents the last two digits of the year (e.g. XX for 20XX).
=>“YYY’ represents for serial number of the PQR report.

Annexure: Product Quality Review

N/A

Product Quality Review Read More »

Environment, Health & Safety Procedure

Environment, Health & Safety, Purpose :

Environment, Health & Safety, To establish a system for the environment, health and safety procedure. This covers the various steps that are required to be followed for EHS policy.

Environment, Health & Safety, Scope :

This procedure is applies for all the employees, visitors, suppliers, contractual third party employee and all the persons enter into the premises of XX Pharmaceuticals Limited (Both General and Cephalosporin Block).

Definitions / Abbreviation:

[][]QA : Quality Assurance
[][]QC : Quality Control
[][]PD : Product Development
[][]EHS : Environment, Health and Safety

Responsibilities:

[][]The roles and responsibility is as follows:

All Concerned Personnel

[][]To be responsible to follow the SOP

Emergency Response

[][]Team Member
[][]Key personnel to perform their duties as per procedure

Head of Plant Operation

[][]Responsible to ensure the overall procedure

Head of Quality Assurance

[][]Responsible to Assurance the overall procedure

Procedure:

[][]All the concerned personnel to be followed the updated systems for safety, health and environmental Hazards & risks associated with activities and products.
[][]All the personnel should be followed the improve conditions in order to prevent accidents, health hazards & pollutions.
[][]Everyone should be aware of minimization of waste generation, promote recycling and green Chemistry.
[][]Every personnel should be well known about energy consumption.
[][]Reduce harmful solids, liquids and gas generation.
[][]Safety awareness to be created to our suppliers and customers.
[][]The best extent possible to work with suppliers who themselves have sound safety, health and environmental policies.
[][]To set environmental, health and safety objectives and targets by all departments to improve EHS Performance.

Periodic Health Check-up

[][]After the employment of a new employee, health check-up is conducted by plant physician.
[][]Every employee, particularly production, QA, QC, PD and Warehouse department personnel will have to undergo health examination include health status and personal health history.
[][]Health examination covers general status, respiratory tract status, eyes status, skin cleanliness, cephalosporin sensitivity test.
[][]Personal health report covers the details history of his/her health status.
[][]Health report will be preserved by Executive, HR & Admin.
[][]General frequency of health check-up: At least twice a year.

Personal Hygiene

[][]Any person shows at any time to have an apparent illness or open leisions that may adversely affect the quality of products is not be allowed to handle starting materials, packaging materials, in-process materials or drug products until the condition is no longer judged to be a risk.
[][]All employees will report to their immediate supervisor about any conditions (relating to plant, equipment or personnel) that they consider may adverse effect the products. Health, safety and environment department manage record/documentation of each employee’s health status and maintain the record/documentation updating.
[][]Direct contact is avoided between the operator’s hand and starting materials, primary packaging materials and immediate or bulk product. All personnel are trained in the practices of personnel hygiene.

Emergency Responses

First Aid:

[][]All injuries, regardless of how small, must be reported and treated as soon as possible after an injury.
[][]First Aid facilities are located throughout the working areas.
[][]Supervisor will show his/her employee for the facility locations. If anyone becomes injured or ill any here due to an industrial or non-industrial problem and need immediate medical aid, he/she has to report the Emergency Responses Team and go to the nearest first aid facility the medical department or the security desk.
[][]If the immediate aid is not needed, notify his/her supervisor before proceeding to the nearest first aid facility.
[][]Whenever outside medical assistance is needed, designed first aid responder as per annexure-1 or plant head will call for this assistance.

Fire Emergency Procedure

[][]Every employee will be familiarize themselves during their induction training period with the location of the evacuation routes(Primary &Secondary),first aid station or kit, each fire alarm, each fire extinguisher, the nearest public telephone and the location of the stairway (as indicated on the emergency evacuation Diagrams).
[][]If any person discover fire anywhere in the building, immediately active the nearest fire alarm pull box and call the HR & Admin. State his/her name, location and type of fire.
[][]Only consider attempting to extinguish a fire if it is a very minor and every person should have been trained in the proper operation and use of portable fire extinguishers.
[][]Use procedure of fire extinguisher.
[][]Pull the pin of the extinguisher.
[][]Stand about six to eight feet from the fire where aim is the hose at the base of the fire.
[][]Squeeze the trigger.
[][]Mount, Locate and identify extinguishers so that they are readily accessible to employees.
[][]Only approved extinguisher shall be used. Maintain extinguisher in a fully charged and operable
[][]Condition and keep in their designated places at all times except during use.
[][]Soldered or riveted shell inverting type extinguisher shall be permanently removed from service.
[][]Extinguisher shall be visually inspected monthly, maintained annually and hydrostatically tested
[][]Periodically by Engineering personnel.

Fire protection and control

[][]All employees shall know the location and be properly trained in the operation of all firefighting equipment.
[][]Portable fire extinguishers shall be suitable to the conditions and hazards involved. They also will be provided and maintained in good operating condition.
[][]Each extinguisher will be serviced at least once a year and tagged and dated and dated to show this.
[][]An approved safety container shall be used for handling flammable liquids up to five gallons.
[][]The employee should immediately leave the area using the designated evacuation route through emergency exit path.
[][]When evacuating no one should use elevators, keep to the right, walk-not to run and remain calm but take immediate action.
[][]A preplanned procedure has been established to assist non-ambulatory individuals and have to obey the directions of building Emergency Response Officials.
[][]Small fires can spread rapidly and overwhelmed an area. To contain the fire close all doors behind exit the building. Before opening any door of a room or office that leads to the main hallway feel the door first to see if it is hot.
[][]Open the windows for fresh air and hang a sheet or other similar article, out the window to let the HR department to know him are still inside.
[][]If all exists from a floor are blocked or if any reason personnel must remain in a room/office during a fire or other emergency and advice of his location and situation. Wait for the fire department to assist him.
[][]After exiting the building get far away from the building, all staff members are to assemble in the emergency assembly point located east or west corner of the plant premises for accountability.
[][]Everyone should remain outside the building until the management staff informs him/her that it is safe to return to the building.
Plant head will count the total present employee as per total employee list provided by HR Executive to become sure that there is no one remains contact in the fire.

Emergency disaster procedure

[][]Everyone will be familiarizing with the location of the evacuation routes(Primary and secondary) the nearest public telephone and the location of the stairway (as indicated on the Emergency Evacuation Diagrams).
[][]Depending on the disaster the watch period should be used to prepare for an easy transition into the nearest designated emergency assembly point.
[][]Plant head will count the total present employee as per total employee list provided by HR Executive to become sure that there is no one remains contact in risk area for easy rescue.

Annexure:

Annexure-I: Emergency Response Team (General Block & Cephalosporin Block)

Environment, Health & Safety Procedure Read More »

Disposal of Materials & Products Procedure

Disposal of Materials, Purpose:

Disposal of Materials, To establish a system for the authorization and disposal of rejected/expired materials and products. This covers the various steps that are required to be followed for destruction of rejected/expired materials and products in a safe and legal way with proper authorization.

Disposal of Materials, Scope:

This SOP applies to quality related non-complies or undesirable materials in XX Pharmaceuticals Ltd. (Both General & Cephalosporin Block) from any one of the following interface steps.

Rejected Raw & Packaging Materials

[][]Expired Retention Samples
[][]Manufacturing waste and in process waste (Both raw & packaging materials)
[][]Rejected Intermediate/Bulk Products/Batch Tails/Finished Products
[][]Trial sample for product development
[][]Laboratory waste (Reagent, analysis sample etc.)

Definitions / Abbreviation:

[][]QA – Quality Assurance
[][]QC – Quality Control
[][]PD – Product Development
[][]BMR – Batch Manufacturing Record
[][]Waste – Materials if they no longer are fit for their originally intended purpose.
[][]Non-Waste – Materials that can be recovered and reused in a process.
[][]Hazardous Waste – Waste is considered to be hazardous if it exhibits any of a number of properties related to flammability, explosivity, water/air reactivity, corrosivity, oxidizing potential, acute or chronic toxicity, ecotoxicity or infection.
[][]Non- Hazardous Waste – Waste is considered to be non-hazardous if it DOES NOT exhibit any of the properties related to flammability, explosivity, water/air reactivity, corrosivity, oxidizing potential, acute or chronic toxicity, ecotoxicity or infection.

Responsibilities:

[][]The roles and responsibility is as follows:

Concerned Department

[][]To collect, disposition and proper storage & disposal of rejected materials/products according to this SOP.

Quality Assurance

[][]To review and get prior approval for initial disposition.

HR Executive

[][]To check and monitor regular disposition activities

Senior Executive, Cost & Budget (Factory)

[][]To verifying that all the disposed items and make report for stock adjustment memo.

Head of Plant Operation

[][]Proper follow-up of overall activities

Head of Quality Assurance

[][]Approval of all the disposal activities

Procedure:

Precautions / Special instructions

[][]Wear masks, gloves & safety goggles (eye protective glasses) and other necessary precautions during destruction works and disposal of wastage and expired materials/products.
[][]Avoid scattering after completion of work.
[][]Always keep the plastic bucket/dustbin covered with lids after work.
[][]Wash the container after completion of work.
[][]Do not dispose the waste tablets and capsules directly into drain.
[][]Do not store the in-process waste for disposal for next day.

Disposal procedure for manufacturing & In-process waste from production area

[][]Departmental executives/ operators will ensure that the waste materials are segregated at sources of generation as hazardous & non-hazardous.
[][]Departmental executives/ operators will ensure the waste materials are in their respective designated containers and their physical segregation from passed, approved, quarantined or any finished good materials. They will also separate solid & non-solid waste materials.
[][]In case of new product, Product Development will assess and identify the nature of materials as hazardous & non-hazardous at development stage. Product [][]Development will notify the relevant owners about the disposal procedure of wastes.
[][]The waste packaging materials (polythene bags/cartons/labels/drums/fiber board boxes etc.) will be removed daily from the sections and transferred to salvage yard according to nature of disposal process by service people.

[][]The manufacturing related solid waste materials (waste raw materials, products, IPC materials etc.) will be removed daily from the sections.
Each working area contains separate waste bin with proper labeling for different types of waste as per annexure-V.

[][]Put all the tablets checked during in process check (IPC) for hardness, thickness, friability and weight variation in waste bin placed in respective compression room, IPC room. The same procedure will be applicable for capsule, powder for suspension, rejected tablets, and capsule from blister area and bottles which are used for leak test.
[][]Collect the dust from Dispensing, Granulation, Compression, Encapsulation and Powder filling area in the waste bin placed in the respective area except hazardous waste.
[][]Take all the waste in the washing area. Production & QCOM Executive will be present during disposal and follow up the whole activities.
[][]Take approximately 10 – 15 liters of potable water into a bucket. Dissolve any types of waste mentioned above in this water in quantity sufficient.
[][]After dissolving, transfer the dissolved wastes into washing area and dispose them into drain with plenty of water to ensure proper cleanliness of the drain.
[][]Clean the bucket using Sodium bi carbonate & Sodium Lauryl Sulphate (detergent) powder solution.
[][]Dispose the dust or tablets or capsules collected in a vacuum cleaner in the same way as described above.
[][]The manufacturing waste should have to be disposed immediately the same day of waste produced.
[][]Disposal procedure for laboratory waste (Reagent, analysis sample etc.)
[][]For laboratory waste follow the SOP “Waste management in Quality Control Laboratory” Where XX denote current version.
[][]Disposal procedure for waste generated in the Product Development Laboratory
[][]For the waste generated in the PD laboratory follow the SOP “General waste disposal procedure for product development lab.”  Where XX denote current version.
[][]Disposal procedure for intermediate/bulk products/batch tails/finished products/hazardous waste from manufacturing area
[][]When a finished product/ intermediate products/ bulk product/ batch tails, hazardous waste is to be rejected, the concerned department Head shall raise “Disposal Form for Materials & Products” as per annexure-I for write-off in the part-A.
[][]The form is first to be signed by Concerned Department Head followed by concerned personnel of Factory Accounts & Budget, HR & Admin personnel, General Manager plant and approved by Head of Quality Assurance.
[][]After approval of the Disposal Form for Materials & Products, concerned department will attached the “To Be Disposed” label as per Annexure-III with the rejected materials and to be kept in a dedicated area of the respective production department before the schedule for disposal activities.

[][]The disposal activities to be carried out in the concerned department in the respective washing area.

[][]All the disposal activities will be conducted in a dedicated washing area with direct supervision of QA Executive

Tablets, Capsules & PFS : Non-Betalactam

[][]Wear appropriate Personal Protective Equipment/Clothes.
[][]Sort out the blister strips of tablets & capsules.
[][]Tear the blister strips and take out the tablets from the pouches.
[][]For PFS: Open the Alu. Cap & tear the label.
[][]Pour the powder of the bottles into a plastic bucket.
[][]Keep aside the deformed Alu. Cap, LDP stopper & spoon and send to salvage yard.
[][]Keep the Dry powder, tablets and capsules in a bucket; mix/dissolve the tablets/capsules with water and stirring.
[][]Neutralize the liquid (pH 6 – 9) by using acid/alkali. Dilute 10 – 20% of the liquid by fresh water and drain out with plenty of water or burg.

[][]Tear the printed packaging materials and transfer all the torn packing materials to the salvage yard.

Tablet, Capsules and PFS (Cephalosporin)

[][]Wear appropriate Personal Protective Equipment/Clothes.
[][]Make sufficient quantity of 0.4% (v/v) sodium hypo-chlorite solution.
[][]Sort out the products.
[][]Take out the strips from the cartons.
[][]Tear the blister strips and take out the capsules/tablets & keep in a bucket.
[][]Keep the torn blister strips into a polythene bag.
[][]For PFS: Open the Alu. Cap, LDP stopper & tear the label.
[][]Pour the powder of the bottles into a plastic bucket.
[][]Keep aside the deformed Alu. Cap & spoon and send to salvage yard.
=>Dissolve/mix the dry powder, tablets and capsules in a covered plastic bucket with previously made 0.4% (v/v) sodium hypochlorite solution and stir with a rod. Leave it overnight for at least 12 hrs.
=>Neutralize the liquid (pH 6 – 9) by using acid/alkali. Dilute 10 – 20% of the liquid by fresh water and drain out slowly the materials on the following working day.
=>Clean the drain with adequate water flushing.
=>Tear all packaging materials and transfer the torn packaging material for salvage yard.
[][]After disposal of the product/ materials, Part B of the Disposal Form for Materials & Products shall be signed by concerned person with designation who disposed the products and then jointly checked by Executive, QA and Executive, HR & Admin. and finally approved by Head of QA.
[][]All master copy of disposal records shall be maintained and kept by QA department and another copy will be sent to Concerned Department, HR & Admin Department and Cost & Budget (Factory) department.

Expired Retention Samples

[][]For expired retention sample the same procedure to be followed the procedure stated in 7.4 by raising the Authorization and Disposal Form for materials & products.

Waste Packaging Materials

[][]Collect all the in-processed waste produced from packaging area from the waste bin placed in the respective area.
[][]Tear the wastage label, carton, leaflet and put into a polythene bag by attaching “To Be Disposed” label as per Annexure-III.
[][]All wastage of cap, spoon, and dropper are to be deformed and then put into a polythene bag by attaching “To Be Disposed” label. All wastage of foils, films to be cut and put into polythene bag.
[][]All the wastage packaging materials are to be checked by Production and QA Executive daily. Then the daily waste materials sent to the dedicated salvage yard through warehouse with waste material transfer note (Annexure-IV) with proper notification to HR executive.
[][]After receiving of this waste transfer note by HR executive, this copy will be returned to respective department and to be preserved.
[][]All these packaging waste materials are kept in the salvage yard. These wastages are disposed by the third party as per company policy.
This procedure also applicable for the online rejected materials.
[][]In case of large number of online rejected materials the disposal procedure to be followed by prior approval from Head of QA following the Authorization and Disposal Form for Materials & Products.

Stock Adjustment Procedure

[][]After approval of Authorization and Disposal Form for Materials & Products for Rejected Intermediate / Bulk Products / Batch Tails / Finished Products and online rejected materials, stock adjust memo to be filled up by Cost & Budget (Factory) personnel as per Annexure-II.
[][]After approval from relevant personnel the main copy to be kept in the Cost & Budget department and another copy will be attached with the relevant Authorization and Disposal Form for Materials & Products.

[][]Finally the adjustment to be done on the ERP.

Annexure:

Annexure I- Authorization and Disposal Form for Materials & Products
Annexure II- Stock Adjustment Memo
Annexure III- Label for “To be disposed”
Annexure IV- Waste Material Transfer Note
Annexure V- Waste Collection & Disposal Procedure

Disposal of Materials & Products Procedure Read More »

Quality Review Meeting

Quality Review Meeting, Purpose :

Quality Review Meeting, To define the Quality Review Meeting requirements to ensure that the review and escalation of quality and. Assurance risks, improvement opportunities and strategy settings are handled effectively.

Quality Review Meeting, Scope :

This SOP is applicable for holding Quality review meeting of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]CAPA : Corrective Action and Preventive Action
[][]IPC : In-Process Check
[][]QMS : Quality Management System
[][]OOS : Out of Specification
[][]PPR : Periodic Product Review

Responsibilities:

[][]The roles and responsibility is as follows:

Manager, Quality Assurance

[][]Facilitate the Quality Review Meeting.
[][]Prepare the yearly calendar for the meeting.
[][]Recommend the participant list.
[][]Prepare the meeting agenda.
[][]Communicate with the participants for the meeting.
[][]Prepare and issue the minutes.

Manager, Quality Control

[][]Update Environmental monitoring/ Laboratory system/ KPI/ Rejection.

Head of Engineering

[][]Update maintenance status of plant/machinery.

Head of Plant Operation

[][]Chair the Quality Review Meeting.

Head of Quality Assurance

[][]Approve the yearly calendar for the meeting.
[][]Approve the meeting agenda.
[][]Approve the participant list.

Procedure:

Overview of Quality Review Meeting:

[][]Quality Review Meeting is an essential part of the governance and improvement framework for Quality and Regulatory Assurance within XX Pharmaceuticals Limited.

Operation of the Site Quality Review Meeting:

Attendance

[][]It is essential to have adequate senior representation of quality, operational, and supporting roles at the QRM. The ownership of this Quality Review Meeting lies with Head of Quality Assurance. The meeting will be chaired by Head of Plant Operation or his designee.
[][]The Team members of Quality Review Meeting will be all technical person of the Plant. It is essential that the members shall be present in all the meetings. To conduct a meeting at least 70% participation of the members is mandatory. However, either one of i e Head of Plant or Head of Quality Assurance must be present in the meeting.

Frequency

[][]The QRM will be held on monthly basis. A yearly calendar will be followed, which will be issued at the beginning of the year. The responsibility lies with Head of Quality Assurance.

Meeting Process and Communication

[][]It is the responsibility of Head of Quality Assurance to notify the members of QRM a week before the meeting with agenda (Annexure I).
[][]The members will give their feedback on their part of actions at least three days before the
[][]meeting to the Head of Quality Assurance. This will facilitate the process of updating the previous meeting.

[][]The minutes will contain the following attributes:

For actions and decisions

=>Owner (a single name in preference to group actions)
=>Content
=>Context for full understanding/reason including related agenda item.
=>Current status of action
=>Target completion date

Record Maintenance

[][]Manager, Quality Assurance will maintain all records of the Quality Review Meeting as per SOP for Document Archiving, Retention, and Retrieval & Destruction. Following records will be maintained:
=>Minutes
=>Actions taken
=>Decisions taken
=>Communications

Brief Description of Agenda items

Review of CAPA status

=>Review actions for most significant CAPAs
=>CAPA update on Level of internal audits
[][]Changes to regulatory requirements
=>Quality Review Meeting will Review of any new regulatory requirement that is to be addressed.
[][]Quality Management System
=>Confirm that the review of current practices/standards gaps versus the QMS is rigorous.
=>Review actual QMS performance versus target.
=>Review significant changes within the QMS.

Risk Management – Governance and Improvement

[][]Risk Register: The Quality Risk Register must be reviewed to ensure
=>Risks are being identified.
=>Risks are being assessed.
=>Action plans are being progressed.

[][]Periodic Review of QRM Plan
=>Schedule adherence of QRM Plan
=>Endorse new Quality Plan and any change in Quality plan

[][]Quality KPI Review
=>Batches Not Right First Time (Process & Testing error)
=>Batches Not Right First Time (Documentation error)
[][]Change Controls
=>Review the overall status of Change Control Tracker and ensure there is no overdue.
=>Endorse the final closing of Change Control
=>Review all critical and major change controls.
=>Check that the closure is timely and the actions taken are effective

[][]Deviations, Out of Specifications, Rejects and Reworks
=>Quality Review Meeting will
=>Review deviations, OOS, rejects and reworks
=>Assure itself that reporting is full and complete and that closure is timely (Investigation will not open more than 30 days).
=>Review overall trends and set strategic improvement actions.
[][]Complaints – Vendor and Customer
=>QRM will Ensure that all vendor and customer complaints are reviewed.
=>Ensure that any ‘unofficial’ complaints or comments are reviewed
=>Review the root cause and proposed CAPA
=>Review overall trends and set strategic improvement actions.
=>Review Recalls and Product Incident Review. .
=>Understand and endorse resultant CAPAs.
[][]Periodic Product Review
=>Quality Review Meeting will review.
=>Schedule adherence for the year, and monitor timely completion.
=>Key findings (executive summary) of PPR.
=>Improvement recommendations (CAPA) in PPRs are actioned and tracked.
=>Adverse quality trends are reviewed and actioned.
=>Positive quality trends are reviewed to ensure sustainability (or transfer of a good practice).
=>Correlate change controls with product quality trends.

[][]Validation
=>Schedule adherence of VMP
=>Issue triggered from validation
[][]Stability Studies
=>Review stability test status.
=>Review any adverse stability data and assess impact on product quality and shelf life
=>Take corrective action to mitigate the risk.
[][]Environmental/Utility Issues
=>Review any adverse trend of environmental monitoring results and results of water testing and to assess impact on product quality.
=>Take corrective action to mitigate the risk.

[][]Training
=>Progress against plan (Schedule adherence)
=>Man-hours utilized Retention & Archiving of Documents
[][]Retention & Archiving of Documents
=>Progress against plan
[][]Preventive Maintenance
=>Schedule adherence
[][]IPC Trending
=>Review the monthly IPC observations for any GMP non Compliance
=>Review the IPC observation trend to minimize the IPC failure/ error.
[][]Review of last minutes
=>Comments on previous minutes from the participants.
=>Track progress of actions in the previous minutes of the meeting.
[][]Any other matters to discuss
=>Any other matters not discussed earlier but have an impact on product quality.
[][]After Action Review
=>At the end of the meeting members will review the meeting process, confirm whether it has met the purpose and identify the needs for its improvement for the next meeting.

Annexure:

Annexure-I: Agenda of Quality Review Meeting

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Personnel Movement, Documents & Materials Transfer Between Cephalosporin & General Block

Personnel Movement, Purpose:

Personnel Movement, To define the procedure to be applied for the movement of people & transfer of documents & materials between Cephalosporin & General block.

Personnel Movement, Scope:

This document lays down the guidelines for the movement of people & transfer of documents & materials between the Cephalosporin & General block of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]QC – Quality Control
[][]QA- Quality Assurance
[][]QA – Quality Assurance
[][]SOP – Standard Operating Procedure

Responsibilities:

[][]The roles and responsibility is as follows:

All Concerned Personnel

[][]To be responsible to follow the SOP

General Manager, Plant

[][]Proper follow-up of overall activities

Manager, Quality Assurance

[][]Responsible to ensure the Assurance to the procedure.

Procedure:

[][]Where the need arises to move or to transfer documents & materials between the Cephalosporin and General block, care should be taken to prevent contamination, to eliminate the potential sources of contamination. Following provisions have to be maintained in such cases:

Movement of people

[][]Entry of the people working in the Cephalosporin Block is restricted to the General Block during or after their working time. They can enter General Block only before entering the Cephalosporin Block as per requirement.
[][]People working in the General Block can enter into the Cephalosporin Block at any time as per requirement. But it should be maintained that they will not enter again into the General Block at that day.
[][]To transfer any documents / samples / tools / equipment from the General Block to the Cephalosporin Block, the assigned personnel will handover that to the person who work at the lobby area of Cephalosporin Block.
[][]The people working in the lobby area will then handover those to the persons inside the change room.

Transfer of Documents

[][]All the master documents related with Cephalosporin block will be preserved in the document archive room of Cephalosporin Block.
Issuing of BMR, BPR, Logbooks, Forms etc. which control is in the General Block will be done after receiving the requisition from the concerned department to Quality Assurance.
[][]But all the requisition will be performed electronically through mail.
[][]Some common SOPs are shared both by Cephalosporin & General Block. In such cases, all the master copies will be preserved in AGM, QA room of the General Block and controlled copies will be distributed in the Cephalosporin Block.
[][]All signatories will be taken within the Cephalosporin Block.
[][]No documents are allowed to be transferred from the Cephalosporin Block to the General Block. If any document is necessary to be sent to the General Block from Cephalosporin Block (e.g. atomic absorption spectrophotometer reading) it will be sent as an information copy through fax or scan or as a form of soft copy through LAN / Internet.
[][]Before the transfer of materials, the required amount of material is collected & to be placed on a pallet. The material is then transferred manually from General warehouse to the receiving bay of the Cephalosporin warehouse. From the receiving bay, the material is transferred to another pallet (dedicated for Cephalosporin block).
[][]For washed & dried glass bottle or crushed sucrose the same procedure stated in above will be followed.
[][]The pallets/ HDPE drums which were used for transferring materials from the General warehouse can be used only after proper cleaning. These pallets must not be used in the production floor; they will be used only in the warehouse.
[][]For analytical purpose, a set of reference / working standard which is required for analysis must be available in the Cephalosporin QC/ Microbiology laboratory.
[][]Product Development Activities: Any kind of process or product development work related with Cephalosporin product must be conducted within the Cephalosporin block.
[][]Engineering Activities: Any kind of maintenance, calibration activities will be done by the dedicated personnel and equipment’s. In case of single calibration instruments, after finishing the tasks at Cephalosporin Block, all the equipment’s will be transferred to Calibration lab. after proper cleaning and de-contamination.

Annexure:

Annexure I- Inter Departmental Materials Transfer Record
Annexure II- Status Label for Inter Departmental Transferred Materials

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Document Control Procedure

Document Control, Purpose:

Document Control, To describe the procedure for activities involved in the preparation, control, retrieval and archiving of quality related documents.

Document Control, Scope:

This procedure covers all the documents issued by Quality Assurance and it also includes documents related to regulatory, calibration, qualification and validation activities at XX Pharmaceuticals Limited (Both General & Sterile Block)

Definitions / Abbreviation:

[][]QA – Quality Assurance
[][]SOP – Standard Operating Procedure
[][]XX – Current Version of SOP

Responsibilities:

[][]The roles and responsibility is as follows:

Procedure:

[][]This procedure shall be applicable for all the new documents, which are prepared from the effective date of this document. The existing document shall be modified as per this procedure whenever due for periodic review or whenever they need to be revised on need basis.
[][]The layout of the Quality Related documents
[][]The layout of SOPs, calibration, validations, guidelines, QA policies, and qualification should be as per the respective templates.
[][]Formats: The format can be designed according to the data that is to be entered. The document number along with revision number, concerned document reference number shall be placed at the top of each page of the format.
[][]Validation protocols and Reports: The format and contents are described in the procedure for validation protocols and Reports.

[][]Quality related documents are essential documents, which establish the quality systems, and are required as per Good Manufacturing Practices (GMP).
Batch Manufacturing Record (BMR) & Batch Packaging Record (BPR): The format and contents are described in the procedure for Preparation, approval, distribution, control & revision of Batch processing records according to SOP.
[][]Specifications, Method of analysis & analytical work sheet: The format and contents are described in the procedure SOP.

Preparation, review and approval/ authorization of documents:

[][]All documents (new or existing) are to be drafted by appropriately qualified personnel of the concerned department and submit to the head of the department for checking. Before submission for checking, the responsible personnel shall initiate a draft copy.
[][]The department Head shall circulate the draft document to concern section Heads for checking. All the comments / inputs shall be written directly on the draft, signed and dated by the respective persons.
[][]After the draft document has been commented on by all the concerned Heads, a final checking /review is carried out by the QA department.
[][]If there are changes, a further document is prepared and circulated until the final draft is agreed.
[][]Concerned department then shall prepare the final copy and assign sequential number (in case of new documents). In case of existing documents, only the version number will be changed.

[][]The final document shall then be signed by the responsible staff. All the draft copies are to be destroyed subsequently.
[][]Concerned department Head shall send the approved master copy to QA for distribution or Issuance of controlled copies.
[][]QA shall issue the controlled copy of documents to concerned departments.

Standard Operating Procedures

[][]Follow the previous step
[][]Sufficient time is given between issue date and effective date to enable training of concerned people.
[][]Batch Manufacturing Records (BMRs) and Batch Packaging Records (BPRs)
[][]After finalization of Manufacturing Record and Batch Packaging Record shall be prepared by Product Development department.
[][]BMR & BPR shall be drafted by Product Development by using relevant template.
[][]Product Development shall send duly signed master copy of BMR & BPR to QA for distribution or Issuance of controlled copies.
[][]QA shall issue the controlled copy of documents to concerned departments.

Specifications, Method of Analysis

[][]Specification: A list of tests, references to analytical procedures and appropriate acceptance criteria that can be numerical limits, ranges or other criteria to which a material must conform to be considered acceptable for intended use.
[][]Test Procedure: Analytical procedures that are to be followed against any test described in method of analysis.
[][]Each material must have unique specifications and test procedures. The test procedure shall give the details of methods to be carried out against each test parameter defined in the specifications.
[][]QC shall prepare final copy of documents and assign sequential number to all specifications, method and analytical work sheet. These Documents shall be prepared, checked and approved by persons as defined in the responsibility.
[][]QC shall send the duly approved master copy to QA for distribution or issuance of controlled copies.
[][]QA shall issue the controlled copy of documents to concerned departments as per previous step.

Qualification and Validation Documents

[][]Concerned Department shall prepare the Qualification documents by using relevant templates.
[][]After finalization of BMR and BPR concerned QA personnel shall be prepared validation documents by using relevant template.
[][]Other qualification and validation documents shall be prepared, checked and approved by persons as defined in the responsibility.
[][]QA shall issue the controlled copy of documents to concerned departments as per previous step.

Distribution or Issuance of Controlled and Uncontrolled documents

[][]All the GMP documents related to the manufacturing plant will be issued by Quality Assurance. The Controlled copies of documents shall be made by Quality Assurance by photocopying the master copy and sealed as

CONTROLLED
Initial………Date..…

=>in blue ink with initial & date of QA Personnel.

[][]If an additional copy of document is required by any department for operational use then Quality Assurance dept. shall issue an additional copy only after written approval from Head of Quality. Such requests shall be obtained through the Request Form as per Annexure – I.
[][]The controlled copies of new documents shall be distributed to the concerned departments and sufficient time should be given before the effective date of the document to enable training of the concerned people.
[][]All formats shall be controlled by QA. The required number of working format shall be copied from control copy by respective department head or his nominee and reconciliation of copied format shall be done by respective department head or his nominee.

Revision of existing documents

[][]Documents such as SOPs, BMR, BPR etc which requires revision due to change control shall be revised by concerned department.
[][]Revised documents shall be given sequential revision No. and controlled by Quality Assurance.
[][]Documents undergoing change due to regulatory requirements / audit Assurance shall also be revised through proper change control by the concerned department.
[][]QA shall distribute the controlled copies of revised documents to concerned departments as per previous step.

Document Archive

[][]All the master documents will be archived at QA end at the document archiving room of both two blocks. At the archiving room, master documents will be kept after recording the archiving no. in the document archive register as per annexure-V.
[][]In the archive room, master document will be kept in a departmental manner as per allocated area for the individual department.
=>Document archive no. will be given as the following format-
=>GDA/XXXX/YYYY
=>Where, GDA represents as General Document Archive. For Sterile block it will be CDA that’s represents as Sterile Document Archive.

=>XXX represents as the Departmental Code as per following List-

[][]Quality Assurance/QA
[][]Quality Control/QC
[][]Engineering/ENG
[][]Production/PRD
[][]Product Development/PD
[][]Microbiology/MICRO

=>YYYY- represents as sequential number which starts from 001.

[][]Document archive room will be lock & key controlled system. Only authorized personnel of QA department will enter in this room for documents preservation. Any other will take authorization from Head of QA to enter this room for document checking or reviewing.
[][]Retrieval or Recall of Obsolete Controlled copies and Superseding of Obsolete Master documents
[][]When the document has been revised following a change request, the older version must be superseded.
[][]Obsolete versions of documents are retrieved and reconciled and entries are made in the specific obsolete register.
[][]All retrieved controlled copies of documents shall be destroyed immediately & recorded.
[][]The Master Copies of the superseded documents along with document change /approval request form shall be archived in the QA department stamped as in Red Ink maintaining the a register.

OBSOLETE
Initial………Date..…

=>in RED ink with initial & date of QA Personnel.

Document Retention

[][]The Retention period of quality related documents is mentioned in Annexure – II.
[][]All quality related documents should be stored securely and safely with controlled access, protected from damage and mutilation. The storage areas and access restriction to the retention of these documents are in the documents archiving room.
[][]The documents related to legal proceeding should be securely kept till the legal proceeding are over.
[][]All documents relevant to quality of the in-house manufactured products must be included in the documents archiving register having a archiving no.

[][]Quality Assurance shall maintain all the Master documents
[][]Responsible Quality Assurance executive shall maintain a log register for taking & re-archiving of documents from Documentation Archiving Room of QAD.
[][]A log register shall be maintained by responsible Quality Assurance executive to archive the Batch Production Records.

Destruction

[][]QA department shall destroy the documents after the retention period is over and maintain a record of the same.
[][]The destruction may be performed by shredding, cutting, tearing, to make the documents non-usable.
[][]A file note will be prepared. A list of documents with sufficient information like document number, effective date, review date etc. (or manufacturing date, expiry date, batch number or lot number of the materials or products etc.) will be attached as an annexure in the file note. Destruction approval will be given by GM, Plant and Manager, Quality Assurance.

Annexure:

Annexure-I: Request for Issuance of Additional Copy of Documents
Annexure-III: Retention Period of Quality Related Documents.
Annexure-III: Document Control Register
Annexure-IV: Log Register for Obsolete Documents
Annexure-V : Document Archive Register

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Hold Time Study

Hold Time Study, Purpose:

Hold Time Study, To establish a procedure for determination of in-process holding time limits.

Hold Time Study, Scope:

This procedure is applicable for all products to be manufactured at both General block and Sterile block of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]RH – Relative Humidity
[][]NMT – Not more than
[][]QA – Quality Assurance
[][]SOP – Standard Operating Procedure

Responsibilities:

[][]The roles and responsibility is as follows:

Executive, Quality Assurance

[][]To ensure proper handling & storage of hold time sample following this SOP.

Executive, Quality Control

[][]To be responsible to provide analytical support

Manager, Quality Assurance

[][]Approval of the SOP.

Procedure:

[][]Hold time study for dispensed materials (Active materials), blended granules, bulk tablet, coated tablets, bulk capsules, blister strips, filled bottles to be done.

[][]The sampling & testing frequency will be 7 days and 15 days. In addition for blister and filled bottles-60 days study to be performed. Based on the holding time study the holding period will be fixed.
[][]During holding time study all products were considered withstand the controlled environmental condition (The environmental condition is; %RH: NMT 55.0% and Temperature NMT 25deg.C).
[][]If the holding period of dispensed active materials, blended granules, bulk tablets/capsules, filled bottle and blister strips is more than the time period specified in this SOP then further assessment/retesting to be conducted before further proceeding.
[][]However in case of recoverable residue consumption of capsule products the h. study will be conducted up to four months and based on the analytical data the holding period will be fixed.
[][]The numbering of hold time study report for individual products shall be assigned as per
=>HSR/PXXXXX/YY
=>Where, HSR means Hold time Study Report
=>PXXXXX means the product code
=>YY means the version number of the study report.
[][]Sampling, analytical testing shall be conducted according to annexure- I.
[][]Hold time test of dispensed active materials for a product of different strengths will be done once.
[][]Data shall be compiled and used for establishing in-process holding time limits for different stages of product manufacturer.
[][]The  H. study for equipment should be performed and both clean and unclean state of equipment also be considered. Based on the documented data the equipment holding time period will be established.
[][]After collecting all data the H. time study report will be generated for each product following the annexure-II.

Annexure:

Annexure-I: Sampling stage and testing frequency for hold time study
Annexure-III: Hold time study Report format

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Retention Sample Handling

Retention Sample, Purpose:

Retention Sample, To establish general guidelines for sampling, handling and storage of Retention sample of finished products for regulatory testing and for resolution of customer complaints.

Retention Sample, Scope:

This procedure is applicable for both General block and Sterile block at XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]BPR: Batch Packaging Record
[][]QA: Quality Assurance
[][]QA: Quality Assurance

Responsibilities:

[][]The roles and responsibility is as follows:

Executive, Quality Assurance

[][]To ensure proper handling & storage of retention sample following this SOP.

Manager, Quality Assurance

[][]Approval of the SOP.

Procedure:

[][]At the start of packaging operation, retention sample of every batch for different dosage form shall be taken by the Quality Assurance personnel engaged in In-process checking as follows-

[][]Tablet: Not less than 60 Tablets (Equivalent to unit packs)
[][]Capsule: Not less than 60 Capsules (Equivalent to unit packs)
[][]Powder for Suspension: Pack size is 35ml or less- 6 unit packs & Pack size is above 35 ml- 4 unit packs
[][]Kidney Dialysis Fluid: 1 Pack (10 L)
[][]Liquid Sterile: Not less than 60 ml (Equivalent to unit ampoule or pack)
[][]Sterile Powder for Injection: Not less than 10 unit packs

[][]Retention samples of finished product shall be collected from each part (i.e., each type of pack -commercial, trial aid, export, institutional, etc.) of a batch. During collection of retention sample followings shall be considered –
[][]Full retention sample shall be collected from first time packaging whether it is commercial or export.
=>One or two unit packs shall be collected from next each part.
=>Representative samples shall be collected from any pack of export or trial aid pack.
[][]Quantity of the retention sample shall be recorded and signed with date on Batch Packaging Record by the concerned Quality Assurance executive.

[][]Quantity of the retention sample shall be recorded and signed with date on Batch Packaging Record by the concerned Quality Assurance executive.
[][]The samples shall be sent to retention sample store after keeping record into the “Annexure-I: Retention Sample Archiving Log Book” of specific Quality Assurance station.
[][]Before archiving the retention sample in the specific rack, entry shall be given for Product name, quantity, Batch No., Mfg. Date and Exp. Date. At the same time, Serial No. shall be given on the outer side of the carton/pack of retention sample for easy identification.
[][]Serial number of retention sample shall be given as follows-

GR/XX/YYY
Where,
=>“GR” stands for General Retention (For Sterile Block it will be CR)
=>“XX” stands for the last two digit of the year. It will be changed for next year.
=>For example- AA for year 20AA, BB for 20BB and so on.
=>“YYY” is the sequential number. In every new year it will be started from 001 and so on.

[][]Retention sample of each batch shall be kept up to the product shelf life plus one year (minimum).
[][]The Retention samples shall be stored under ambient temperature of the retention sample store (Temperature should be NMT 30ºC). For sterile powder for Injection products this room temperature will be controlled as not more than 25º C.
[][]Temperature of Retention sample store shall be recorded in “Annexure-II: Temperature Record Sheet” regularly (at least two times in a day i.e. at 9:00 AM and 4:00 PM) using calibrated thermo hygrometer. At the same time maximum and minimum temperature shall be recorded at 8:30 AM in each day.
[][]Requisition for Retention sample shall be raised through Annexure-III: Requisition Form for Retention Sample. Samples/Documents shall be provided to requester dept. after getting approval of Head of Quality Assurance. No of supplied retention samples to be recorded in the retention sample register.
[][]After the stipulated storage time (Shelf life plus one year), all the retention samples will be discarded through the SOP of “Procedure for disposal of material and products”, SOP.

Annexure:

Annexure-I: Retention Sample Archiving Log Book
Annexure-II: Temperature Record Sheet
Annexure-III: Requisition Form for Retention Sample

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Batch Issuance Procedure

Batch Issuance, Purpose :

Batch Issuance, The purpose of this SOP (Standard Operating Procedure) is to provide a documented procedure for issuance of BMR and BPR.

Scope :

Batch Issuance, This procedure is applicable for issuance of BMR and BPR at XX Pharmaceuticals Limited (Both General and Sterile Block).

Definitions / Abbreviation:

[][]BMR: Batch Manufacturing Record
[][]BPR: Batch Packaging Record
[][]QCOM: Quality Assurance

Responsibilities:

[][]The roles and responsibility is as follows:

Executive, Quality Assurance

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Manager, Quality Assurance

[][]To ensure implementation of the SOP.

Manager, Quality Assurance

[][]Approval of the SOP.

Procedure:

[][]Issuance Procedure of Batch Manufacturing and Packaging Record (BMR/BPR).
[][]Fill up the respective BMR/BPR details in requisition form (Annexure-II) with signature of user and send to C for the issuance of respective BMR/BPR.
[][]On receipt of BMR/BPR requisition form from production department, QA shall enter the issuance entry in BMR/BPR issue register and then, photocopy the required copy of respective product BMR/BPR from the master copy of BMR/BPR.
[][]QA personnel shall enter the information related to Batch like Batch Number, Manufacturing Date, Expiry Date to photocopy of BMR/BPR.
[][]Send the photocopy of BMR/BPR to production department.

Annexure:

Annexure-I: Batch Issuance Register
Annexure-II: Batch Requisition Form

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Risk Assessment Procedure

Risk Assessment , Purpose :

Risk Assessment , The objective of carrying out the Risk Assessment is to ensure the potential threats to the product quality/ supply are properly assessed and appropriate control measures are in place.

Risk Assessment , Scope :

This procedure applies for the risk assessment of facilities, utility services, equipment & machinery, warehousing, manufacturing, packaging, testing and transfer of quality products from at XX Pharmaceuticals Limited (Both General and Sterile Block).

Definitions / Abbreviation:

[][]Risk assessment: Risk assessment consists of the identification of product quality risk and evaluation of risks. Quality risk assessments begin with a well-defined problem description or risk question. When the risk in question is well defined, an appropriate risk management tool and the types of information needed to address the risk question will be more readily identifiable.

Responsibilities:

[][]The roles and responsibility is as follows

All concerned department heads

[][]To perform the risk assessment associated in his area in a cross-functional team, including one QA personnel as a mandatory member.

Manager, Quality Assurance

[][]To ensure that proper risk assessment is done if there any potential risk(s) involved in the product quality/ supply.

Head of Quality Assurance

[][]Approval of the SOP.
[][]Implementation of risk assessment procedure

Procedure:

=>Risk assessment: Risk assessment consists of the identification of product quality risk and evaluation of risks. Quality risk assessments begin with a well-defined problem description or risk question. When the risk in question is well defined, an appropriate risk management tool and the types of information needed to address the risk question will be more readily identifiable. As an aid to clearly defining the risk(s) for risk assessment purposes, three fundamental questions are often helpful:
[][]What might go wrong?
=>Output for Question 1: Problem/ Failure descriptions- Cause – Failure mode – Effects
[][]What is the likelihood (probability) it will go wrong?
[][]What are the consequences (severity)?
=>Output for Question 2 & 3: Risk Class, Job/Action Priority, Failure rates, Risk priority number (RPN).

[][]Risk identification: Risk identification is a systematic use of information to identify product quality risk or problem description. Information can include historical data, theoretical analysis, informed opinions, and the concerns of stakeholders.

[][]Risk analysis: Risk analysis is the estimation of the risk associated with the product quality. It is the qualitative or quantitative process of linking the likelihood of occurrence and severity of harms. In some risk management tools, the ability to detect the harm (detectability) also factors in the estimation of risk.

[][]Risk evaluation: Risk evaluation compares the identified and analyzed risk against given risk criteria. Risk evaluations consider the strength of evidence for all three of the fundamental questions.

[][]The output of a risk assessment is either a quantitative estimate of risk or a qualitative description of a range of risk. When risk is expressed quantitatively, a numerical probability is used.

[][]Alternatively, risk can be expressed using qualitative descriptors, such as “high”, “medium”, or “low” (Risk class one, Risk class two or Risk class three) , which should be defined in as much detail as possible.

[][]Sometimes a “risk score” is used to further define descriptors in risk ranking. In quantitative risk assessments, a risk estimate provides the likelihood of a specific consequence, given a set of risk-generating circumstances.

[][]Thus, quantitative risk estimation is useful for one particular consequence at a time.

[][]To access and manage risk the following recognized tools will be applied:
=>Risk ranking and filtering will be applied for qualitative (High, Medium or low) risk analysis.
=>Failure Mode Effect Analysis (FMEA) will be used for quantitative estimate of risk. (Score of RPN).
=>Fish Bone Diagram/ Cause & Effect Diagram Analysis

Procedure for Risk ranking and filtering:

[][]Identify the key stages for the part of the supply chain for which the company has responsibility from material supply through to use of product by patients & customers.
[][]Identify potential threats that could impact the product quality or security at each key stage.
[][]Estimate the consequences both in terms of threats and opportunities may be high, medium or low.

[][]Evaluate the exiting control measures for their effectiveness at controlling the threats.
[][]Determine the risk to product quality associated with each threat.
[][]Establish a plan for the introduction of improved controls (additional control measures) where existing threats are not adequately addressed.
[][]Implement the additional control measures and monitor their effectiveness.
[][]To identify the threats the following points should be considered:
=>Patient : Hazard/ risk to the patient safety, patient compliance.
=>Personnel : Attributes, training, education, competence, communication
=>Equipment : Type, design, condition, capacity, location, installation, operation, maintenance & calibration.
=>Facility : Layout, utilities, maintenance, dedication & hygiene.
=>Methods & Procedures : Checking, content, alterations, distribution, utilization, condition, change control, storage, trends, handling planned & abnormal events.
=>Materials : Identity, status, control, quantity, handling, specification, security arrangements, counterfeiting controls & material condition.
=>Environment : Physical effects of climatic & storage conditions (temperature, time, humidity, rain, air pressure, light, vibration etc.), pest infestation, contamination, and damage due to fire or natural disaster like flood, tornado, earthquake etc.

[][]When threats have been identified and commented upon, the table in Annexure – I should be completed.
[][]A judgment should be made on the severity of the consequences & the probability/ likelihood of the adverse events occurring taking into consideration any current control measures that are in place. Each of this can be “low”, “medium”, or “high”.
[][]Considering the severity and probability/likelihood of the events risk will be expressed Risk class one, Risk class two or Risk class three (or, High risk”, “medium risk”, or “low risk).
[][]Risk filtering will be done considering the Risk class (i.e. Risk class one, Risk class two or Risk class three) and detection of the events. Jobs/ actions will be prioritized as High priority, Medium priority or Low priority.
[][]All the jobs/actions for the changed situation shall be identified with in-depth analysis making sure all the impacted areas and the actions with the documentation requirements are assessed and completion date against all the identified actions are set.
[][]Below are two matrixes for clear understanding.

Procedure for Failure Mode Effect Analysis (FMEA):

[][]Risk in an FMEA evaluation has three components: Severity, Probability and detection/ detectability. The first step in any risk assessment is to define the component of FMEA
[][]Definition of the components of the FMEA are:
[][]Severity: if a failure were to occur, what effect would that failure have on the product quality and on the patient (if any)?
[][]Probability of occurrence: how likely is it for a particular failure to occur?
[][]Detectability (ability to detect): what mechanisms are in place (if any) to detect a failure if it were occur?
[][]Each of the above components requires clear descriptions and a corresponding scale to rank or score the projected impact (i.e. a scale for Severity; a scale for Probability; and a scale for ability to Detect). In addition, a composite score would then need to be calculated (e.g. severity multiplied by Probability multiplied by ability to detect)
[][]Non sequential number (e.g. 1,3,5,7, 9) will be used for probability and detection as the use of non-consecutive numbers allow more distinction between rating (table 2 & table 3) and to put more emphasis on the severity criteria a non-linear scoring scale will be utilized (e.g. 1, 4, 9,16, 25) . Please see table 1 for details.

[][]Table 1: Severity criteria for FMEA

Severity
ValueDescriptionCriteria
1IrrelevantNo impact to product quality and process robustness
4SlightNo impact to product quality
9ImportantNoticeable impact to product quality, but can be recovered by reprocessing
16CriticalDefinite impact to product quality that may require rework
25DisastrousBatch failure, not recoverable by rework

Note: Criteria in the above table will be changed based on the subject under assessment

[][]Table 2: Probability criteria for FMEA

Probability
ValueDescriptionCriteria
1An unlikely probability of occurrenceFailure has never been seen in any relevant lab experiments, or scale-up batches yet but it is theoretically possible.
3A remote probability of occurrenceFailure only seen once or twice in relevant lab experiments, never in scale-up batches.
5An occasional probability of occurrenceFailure potential has been noted in several relevant lab experiments, or at scale-up. If procedures are followed the failure potential is minimal.
7A moderate probability of occurrenceFailure potential has been noted in several relevant lab experiments, or at scale-up, in-process control maybe required to avoid failure.
9A high probability of occurrenceFailure potential has been noted in several relevant lab experiment, or at scale-up, an active non-standard feedback control loop may be required.

Note: Criteria in the above table will be changed based on the subject under assessment

[][]Table 3: Detectability criteria for FMEA

Detection
ValueDescriptionCriteria
1High degree of detectabilityA: Validated automatic detection system that is a direct measure of failure.
B: Two or more manual operated validated detection systems, direct or indirect. (e.g. Control range and IPC)
3Good detectabilityA: Single manually operated validated detection system that is a direct measure of failure. (e.g. IPC of failure, validated PAT)
5Likely to detectA: Single manually operated validated detection system that is not a direct measure of failure.
(e.g. PAT measurements or IPC's not directly linked to failure)
7Fair detectabilityA: Non validated (manual or automated) detection.
(e.g. visual level check, visual inspection of vessels).
9Low or no detectabilityNo ability to detect the failure

Note: Criteria in the above table will be changed based on the subject under assessment

Risk Scoring Matrix

[][]The composite risk score for each unit operation step is the product of its three individual component ratings: severity, probability, and detection. This composite risk is called a risk priority number (RPN).
RPN = S x P x D (S= Severity; P= Probability & D= Detection)
[][]The RPN number is not absolute and should be considered in context with other factors that influence the product risk outside the scope of this evaluation. The RPN provides a relative priority for taking action – the bigger the RPN, the more important to address the corresponding failure being assessed.

[][]The table in Annexure – III will be used for FMEA. For each formulation component or manufacturing processing step under evaluation, the function of the component or processing step, potential failure mode and effect of the failure mode should be recorded.

[][]A severity score is then assigned. The root cause of the failure is described and a score is assigned to the probability of occurrence of the failure. Controls that are currently in place to detect the failure are listed and a detection score is then assigned.

[][]The RPN number is calculated. The action(s) that need to be taken to reduce or mitigate the risk are listed and individuals or departments responsible for implementing the actions are identified with target dates for completion.

[][]All the actions for the changed situation shall be identified with in-depth analysis making sure all the impacted areas and the actions with the documentation requirements are assessed and completion date against all the identified actions are set.

Fish Bone Diagram/ Cause & Effect Diagram Analysis

[][]The root cause analysis tool used for major or critical deviation, OOS, market complaint to identify quality defect prevention and potential factors causing an overall effect. Each cause or reason for imperfection is a source of variation. Causes are usually grouped into major categories to identify these sources of variation.

Defining “Effect”

[][]The first step in using the fishbone diagram as a problem solving tool is to clearly define your effect, or outcome that you don’t like. This could be a quality issues, not meeting metrics or troubleshooting the introduction of a new process or product line. This becomes the “head” of the diagram. Use butchers paper or a whiteboard to sketch out the fishbones template.

[][]Defining an effect takes a little practice. Make sure it is brief and succinct. Use facts and numbers where possible. Spend a few minutes reflecting on your effect with the team; does everyone agree that the statement defines the problem as fully as possible?
Brainstorming the “Causes”
[][]With your team, we want to add the bones to this diagram, brainstorming all of the possible influencing factors. Each idea needs to be put into a category or branch.
[][]The following probable categories to be assessed the probable causes through brainstorming is also known as 6M as per annexure-IV
=>Man
=>Machine
=>Method
=>Measurement
=>Material
=>Mother Nature

[][]Man/People/Personnel: Everyone involved with the process across the value stream, including support functions Processes / Methods: This defines how the process is performed and the all requirements needed for doing it, including quality procedures, work orders / travelers / work instructions, drawings.
[][]Machines / Equipment: All machines and equipment, needed to accomplish the job, including tools.
[][]Materials: Raw & Packaging materials, purchased parts and sub-assemblies that feed into the end product.
[][]Measurements: defines how have we determined that the outcome is wrong.

[][]Mother Nature: The standard one which turns to wrong or deviation of the standard outcome
[][]As the team suggests possible causes, determine which heading that idea belongs under, jotting it down clearly. Also add another branch, covering “why” that cause would influence the effect we are investigating. Continue until the team runs out of ideas.

[][]If is there any branches of the diagram that are missing, develop into that area further, asking questions; “Is it possible that the environment has affected our problem” too hot, too cold, too wet?
Document Numbering
[][]The unique document numbering for Risk Assessment shall consist of 9 (nine) alpha-neumerical characters, broken down as follows –
=>e.g. RA/XXX/YY
Where,
=>RA is the Risk Assessment
=>/ is separator
[][]XXX is the sequential number starting from 001, 002 & so on for a calendar year which will be further start from 001 for the next year.
=>YY is the last two digits of the year
=>For example; RA/001/YY
=>Here RA means Risk Assessment
=>001 is the sequential number
=>YY represents for the year 20YY
[][]QA shall issue the Risk Assessment document number and maintain the log register (Annexure – II).

Annexure:

Annexure-I: Risk Assessment Table and Action Plan
Annexure-II: Log Register for Risk Assessment
Annexure-III: Risk Assessment Table and Action Plan
Annexure-IV: Fish Bone Diagram Chart

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Rework and Repackaging Procedure

Rework, Purpose :

Rework, To establish general guidelines for reprocessing, reworking of a full batch or part of a batch of product of an unacceptable quality from defined stage of production so that its quality may be rendered acceptable by one or more additional operation and to set forth method for repackaging of product with proper approval & proper documentation

Rework, Scope :

This procedure is applicable for concern department at XX Pharmaceuticals Limited (Both General and Sterile Block).

Definitions / Abbreviation:

[][]Reprocessing: Reprocessing means the reworking of all or part of a batch of product of an unacceptable quality from a refined stage of production so that its quality may be rendered acceptable by one or more additional operation.
[][]Reworking: Reworking is taking an out of spec. of product and running it through a non–standard process to bring it back in to spec.
[][]Repackaging: Repackaging requires that the final bulk product/ final product be repacked into a specific size or configuration for a special customer order.
[][]SAF: Sample Advice Form
[][]QA: Quality Assurance

Responsibilities:

[][]The roles and responsibility is as follows:

Production

[][]To ensure that Reprocessing/Reworking and Repackaging is done following this SOP.

Concern Department Head

[][]Responsible to perform the job accordingly

Quality Assurance

[][]To monitor and implementation of the procedure

General Manager, Plant

[][]To ensure that the implementation of the procedure as per SOP.

Manager, Quality Assurance

[][]Approval of the SOP.
[][]To ensure that the implementation of the procedure as per SOP.

Procedure:

[][]Acceptable Reasons for Reprocessing
[][]Granules or Powder: Granules or Powder shall be reprocessed / reworked to correct uniformity of mixing, uniformity of fill wt. and potency to achieve required quality of granules.
[][]Plain and core tablets: Plain and core tablets shall be reprocessed to correct poor appearance, thickness, weight, hardness to improve content uniformity, disintegration or dissolution rate.
[][]Coated tablets: Coated tablets may be reprocessed to correct poor appearance, disintegration or dissolution.
[][]Capsules: Capsules may be reprocessed to correct weight variation, potency, dissolution rate etc.

Reprocessing/Reworking procedure:

Initiation & Approval of Reprocess/Rework Request form:
[][]If any reprocessing or reworking seems necessary, concerned Department shall raise Reprocess/Rework Request Form (Annexure-I) upon agreement of Product Development Department and Quality Assurance Department.

[][]Each Reprocess/Rework Request Form shall contain a full explanation of the reason for reprocessing and the proposed reprocessing steps.
[][]An investigation shall be carried out by QA with the help of PD and concerned department (if required) to identify the reason and process for reprocessing.
[][]After that the concerned Department Head, Head of PD and General Manager, Plant shall give their comments.
[][]The Reprocessing work shall start only after getting approval of the proposed reprocessing steps from Head of Quality Assurance.
[][]After completion of reprocess, concerned department shall advice Quality Control for analysis through SAF.
[][]When the test result is received from QC, QA shall then give decision about release of the product.
[][]The appropriately filled Reprocess/Rework Request Form (Annexure-I) along with other necessary documents shall become the part of the batch document.
[][]Assignment of Batch No., Manufacturing Date, Expiration Date and Reference No. for Reprocessing/Reworking batch.
[][]In case of reprocessing a part of a batch or full batch, the Batch No. of part shall be the original Batch No.
[][]In case of reprocessing of a product from different batches tails, the batch no. shall be the first batch of among those batches which are to be reprocessed and “R” shall be suffixed for identification of reprocessed batch.

[][]Manufacturing Date of different batches tails that composed/reformed a batch should be within two months.
[][]Reference No. for Reprocessing/Reworking shall be as
RW-001/07/XX
where-
=>RW represents Reprocess/Rework
=>001 represents monthly sequential number
07 represents Month of July. It will be changed in next month
=>XX represents year of 20XX. It will be changed in next year.

Repackaging Procedure (Primary & Secondary):

[][]When any repackaging of product seems necessary, concerned department shall raise proposal through Repackaging Request Form (Annexure-II)
[][]When any finished product (local/export) returned from central store and are required to convert into physician/local/export pack, it shall be processed through Repackaging Request Form (Annexure-II)
[][]An investigation shall be carried out by QA with the help of PD and concerned department (if required) to identify the reason for repackaging and product quality of the part of the batch which shall be repackaged. Necessary analytical work shall be done for repackaging part of the batch by QC (if required).
[][]Concerned Department shall forward sample through SAF (Sample Advice Form ) to QC for analytical work of repackaging part of the batch.
[][]After completion of analytical work, QC shall forward the analytical test result to concerned department.
[][]Concerned Department Head shall forward Repackaging Request Form to PD and subsequently to General Manager, Plant for their comments.
[][]After that, the Concerned Department forwards the Repackaging Request Form along with test result (SAF) to Head of QA for approval.
[][]Reference No. for Repackaging shall be as
RP-001/07/YY where-
=>RP represents Repackaging
=>001 represents monthly sequential number
=>07 represents Month of July. It will be changed in next month
=> YY represents year of 20YY. It will be changed in next year.
=>Finally Repackaging Request Form and related QC test results shall be the part of the batch document.

Annexure:

Annexure-I: Reprocess/Rework Request Form
Annexure-II: Repackaging Request Form

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Artwork Management Procedure

Artwork Management , Purpose:

Artwork Management , To lay down the general guideline about preparation, approval and preservation of artwork, printed specimen and approved color and design standard of printed packaging materials that are required to develop packaging materials for products.

Artwork Management , Scope:

This SOP is applicable for art work development of new as well as existing products of both General and Sterile Block in XX pharmaceuticals limited.

Definition/Abbreviation:

[][]PD : Product Development
[][]PMD : Product Management Department
[][]QC : Quality Control
[][]QA : Quality Assurance
[][]SCM : Supply Chain Management
[][]XX : Current Version

Responsibilities:

[][]The roles and responsibility are as follows:

Marketing Department

[][]Preparation and checking of text for the packing materials.
[][]Raise a change control in case of any change in the existing art work.
[][]Prepare the final art work for regulatory submission.
[][]Design of all art work as per dimension and text.

Product Development Department

[][]Checking the draft art work for dimension and texts.
[][]Checking dummy carton and machine proof sample and shade card.

Quality Control

[][]Generation of packing specification according to approved artwork and shade card.

Quality Assurance

[][]Checking the text of draft, dummy and machine proof sample.
[][]Preparation and timely review of the SOP.

Head of Marketing

[][]Check and review of all Art works.

Head of Plant Operation

[][]Review of all art work.

Head of Quality Assurance

[][]Approval of all art works as per XX specification.
[][]Approval of the SOP.

Procedure:

[][]After receiving product proposal report from PMD, PD will generate Artwork Technical specification according to Annexure–I and send to PMD. PD will also preserve a copy in the product master file.
[][]PMD will generate the artwork as per Artwork Technical specification (Annexure-I) and send two copies artwork to Quality Assurance. PMD will also generate material code in ERP.
[][]Each artwork will contain the respective material code and version no. with signature of PMD personnel.
[][]Quality Assurance will check the artwork and will take comment from PD regarding label claim, pack size, primary packaging information, and width of foil etc. for any new product and new width of foil or new dimension of carton for existing products. For any correction Quality Assurance will forward the artwork copy to PMD department for further action.

[][]After all reviewing, Quality Assurance & PD will sign the artwork and then forward to Head of Plant Operation for checking.
In the meantime, size and shape (dimension) of the Packaging materials will be confirmed by machine trial or by operation with dummy samples. After receiving dummy samples from PMD, PD and Production will work jointly to finalize the size and shape.
[][]PD will provide samples of required size strips/blisters to PMD for preparation of dummy carton when requested.

[][]Head of Plant Operation will review the artwork and send to Head of Quality Assurance for final approval.
[][]Quality Assurance will send one copy of approved artwork to PMD and preserve another copy at QA.

[][]For new product, PMD will raise commercial requisition after getting three month stability declaration from PD. After commercial requisition Supply Chain will find out the source for preparation of shade card.

Selection of Color:

[][]PMD will suggest the color of Printed components by considering the following:
[][]Preferably color shall be dissimilar in different strengths of same product.
[][]Color shall be stable and not fade on storage or during any operation of the material.
[][]Suggested color shall be forwarded to PD and Quality Assurance for comment.
[][]In case of any major anomaly in color selection, final decision shall be taken jointly by PMD and PD.

Approved Color and Design Standard of Printed Packaging material:

[][]PMD will then send 5 standards of packaging materials to Quality Assurance. Quality Assurance will check the text of printed components against approved artwork and give comments. These standards are for:
=>PMD Copy
=>Quality Control Copy
=>Quality Assurance Copy
=>Supply Chain Copy
=>Supplier Copy
[][]Quality Assurance will send one copy of approved shade card along with artwork to QC for preparation of specification.
[][]After approval of specification, QA will send controlled copy of specification along with shade card to QC, PMD, Supply Chain and the Supplier.
[][]For supplier approval / alternate source development, Supply Chain will send source approval document to QC through PMD. Source approval documents are:
=>Duly filled Vendor Questionnaire
=>Vendor Approval Form
=>Certificate of Analysis/ Conformation
=>Supplied list of material

Change Control:

[][]Any change in the printed components like foil/ carton/ leaflet/ label shall be processed following SOP.
[][]Any change in pack size or brand name of the product shall require approval of local Drugs Authority/Regulatory Authority.
[][]When any change in packaging components, PMD and Supply Chain should ensure that following documents will be collected from the supplier through Obsolete Form of Artwork/ Supplier (Annexure-II). Documents are:
=>Previous version of Artwork
=>Previous version of Shade card
=>Previous version of Plate positive
=>When any supplier will be rejected from approved vendor list, Supply Chain will be proceed through Obsolete Form of Artwork/ Supplier (Annexure-II).

Annexure:

Annexure – I: Artwork Technical Specification
Annexure – II: Obsolete Form of Artwork/ Supplier

Artwork Management Procedure Read More »

Line Clearance Procedure

Line Clearance Procedure, Purpose :

Line Clearance Procedure, To ensure that the area and equipment to be used for the dispensing, manufacturing and packing of products are free from remnants of previous product/batch.

Line Clearance Procedure, Scope :

This procedure is applicable for clearance of dispensing, manufacturing, packing area & equipments at XX Pharmaceuticals Limited (Both General and Sterile Block).

Definitions / Abbreviation:

[][]N/A

Responsibilities:

[][]The roles and responsibility is as follows:

Quality Assurance Personnel

[][]Responsible to perform the activities as per SOP.

Concerned department

[][]To maintain procedure as described in SOP

Manager, Quality Assurance

[][]Approval of the SOP.
[][]To ensure that the implementation of the procedure as per SOP.

Procedure:

Dispensing:

[][]Before start of dispensing of raw material/coating material Production Executive shall check the following and keep record in BMR.
[][]Area cleanliness, absence of irrelevant/ foreign material
[][]Equipment cleanliness
[][]Removal of material of previous batch/product from dispensing area
[][]Balance calibration records, daily accuracy check/ function check of balance
[][]Entry in Log book
[][]Status label of material/ component
[][]Cleanliness of container of material to be dispensed.
[][]Quality Assurance Executive shall monitor and then provide counter check/ signature to ensure that line clearance checking has been performed properly by dispensing people and all above stated parameters are satisfactory.

Manufacturing:

[][]For Granulation/ Compression/ Blending of Powder or Pellets/Coating
[][]Before start of any manufacturing operation concerned Production Executive shall check the following parameters and keep the records in BMR.
[][]Area cleanliness, absence of irrelevant/ foreign material
[][]Equipment/ machinery cleanliness
[][]Removal of material of previous batch/product from granulation/ compression/ blending/ coating area.
[][]Balance calibration records, daily accuracy check/ function check of balance
[][]Room Temperature and % Relative Humidity of the granulation/ compression/ blending/ coating area (if applicable)
[][]Entry in Log book
[][]Room display/ Product display

For Powder for Suspension/ Encapsulation:

[][]Before start of any manufacturing operation concerned Production Executive shall check the following parameters and keep the records in BMR.
[][]Area cleanliness, absence of irrelevant/ foreign material
[][]Equipment/ machinery cleanliness
[][]Removal of material of previous batch/product from area
[][]Balance calibration records, daily accuracy check/ function check of balance
[][]Room Temperature and % Relative Humidity of the manufacturing area (if applicable)
[][]Entry in Log book
[][]Room display/ Product display

Packaging:

[][]Before start of any packaging operation concerned Production Executive shall check the following parameters and keep the records in BPR.
[][]Printing Line Clearance
[][]Name of the previous product (to be recorded)
[][]Batch No. of previous product (to be recorded)
[][]Area cleanliness, absence of irrelevant/ foreign material
[][]Entry in Log book
[][]Room display/ Product display

Packaging Area Equipment Clearance:

[][]Area cleanliness, absence of irrelevant/ foreign material
[][]Equipment/ machinery cleanliness
[][]Removal of material of previous batch/product in packaging line
[][]Room Temperature and % Relative Humidity of the packaging area (if applicable)
[][]Entry in Log book
[][]Room display/ Product display

Annexure:

N/A

Line Clearance Procedure Read More »

Batch Release Procedure

Batch Release, Purpose:

Batch Release, This procedure defines the correct procedures for the release and distribution of finished products to ensure Assurance with the requirements of GMP and includes details of the responsibility of the Authorized Persons.

Batch Release, Scope:

This SOP is applied to storage, release and distribution of finished products and it’s supporting activities at XX Pharmaceuticals Limited (Both General & Sterile).

Definitions / Abbreviation:

[][]QA : Quality Assurance
[][]SOP : Standard Operating Procedure
[][]FIFO : First In First Out
[][]COA : Certificate of Analysis

Responsibilities:

[][]The roles and responsibility is as follows:

Production Executive

[][]Check the quantity of the product before transfer into the ware house.
[][]Transfer the finished goods to warehouse.
[][]Issue Transfer Note accordingly

Warehouse Executive

[][]Receive finished goods from the production floor after proper checking.
[][]Keep the finished product into the ware house accordingly.
[][]Transfer the finished goods to central warehouse after getting release note from QA.

Quality Assurance Executive

[][]Check the quantity of the product before transfer into the ware house.
[][]Compilation of Batch Production Record.
[][]Follow the overall batch release procedure.
[][]Quality Control Executive/ Microbiologist
[][]To provide analytical support for various samples drawn for batch release.
[][]Prepare Certificate of Analysis (COA).

Head Of Quality Assurance

[][]Give approval to release the finished goods into the market.
[][]To ensure Assurance of the SOP.
[][]Approval the SOP.

Annexure:

Annexure-I: Checklist for Batch Documentation
Annexure-II: Finished Product Release Note
Annexure-III: Final Inspection Sheet

Procedure:

[][]After completion of packaging operation, finished packed shipper cartons will be stored at the Quarantine area of packaging hall. Production Executive will raise the Finished Goods Transfer Note  to Quality Assurance Department for final inspection mentioning product name, batch number, quantity, master carton number.

[][]The finished product will be transferred to warehouse after physical checking by Quality Assurance Executive according to final inspection sheet (Annexure- III).
[][]Warehouse Executive will check the product name, batch number, quantity, pack size, and label of finished product(s) against the transfer note during receiving.
[][]If all information (Product name, batch number, quantity, pack size, label) of finished product transfer note is matched with transferred quantity, then Warehouse Executive will receive & store the product in QUARANTINE AREA (for finished product) of warehouse maintaining storage condition as per attached product label on the shipping carton.
[][]After completion of full batch packaging, Production Executive will submit the Batch Packaging Record to Quality Assurance Department mentioning the transferred quantity in the BPR for release of the product.
[][]Quality Assurance personnel will review all the documents / parameters according to checklist . If all parameters are found complies, then he/she will compile the full batch production record (BMR, BPR) along with all related documents.
[][]After compilation of the batch documents, QA Executive will entry in the ERP of release note verification and Head of QA will approve the release in the software.
[][]Quality Assurance will attach the Approved Label  in every pallet containing released product. (One labels per pallet).
[][]During reviewing the documents according to the check list, following matters need to be considered.
[][]Batch Manufacturing Record (BMR)
[][]Evaluate all the in-process result are within limit, cleaned/partially cleaned label are available, dispensing weights are accurate & dispensing slip along with print out is available, all manufacturing part has been done as per instruction, all the responsible persons have signed in respective operation stages in BMR.
[][]If any deviation/change control was raised, reference number is recorded in the respective place of BMR.
[][]Review the reconciliation steps are correctly calculated and loss result is justified.
[][]Review the line clearance in each steps of manufacturing and Packaging stages are signed by responsible person.
[][]Review the related Deviation/Change Control is closed and the reference number of this documents are recorded in the respective area of the BMR.
[][]Review the completed BMR is approved by Quality Assurance and Production after completion of operation.
[][]Review the associated documents such as all relevant labels, IPC record, particle count record (If any) is correct and signed. Review all the results are within limit or not. If any results are found out of limit, then related Out of Specification (OOS) is attached with the document.
[][]Review the completed BMR is approved by Head of Production or his/her designate and Head of Quality Assurance or his/her designate after completion of operation.

Certificate of Analysis (COA)

[][]Review the Certificate of Analysis (Chemical and Microbial) is signed and approve by responsible person. Review all the results are within the specification. Review all the print out of QC analysis result attached with COA.

Batch Packaging Record /BPR (Primary and Secondary)

[][]Review all the packaging materials are correctly dispensed and authentication information for packaging start up is correct.
[][]Review the in process checks are routinely performed.
[][]Review the reconciliation steps are correctly calculated and Yield & loss result is justified.
[][]Review the line clearance in each step (i.e. primary packing, secondary packing), inspection and labeling are signed by responsible person.
[][]Review the related Deviation/Change Control is closed check the presence of the Deviation/Change Control reference number into the respective place of BPR.
[][]Review the completed BPR is approved by Head of Production or his/her designate and Head of Quality Assurance or his/her designate after completion of operation.

Review the quantity of the packs and presence of all signatures accordingly.

[][]Head of QA/Designee shall verify the Batch Production Record as per checklist (Annexure-I) for correct entries, reconciliation of quantity, yield, change control, deviation, out of specification (OSS), (if any), in-process checking records analytical test results etc. After reviewing if all the parameters found satisfactory then the Manager, /designee shall release the product for dispatch.
[][]For dispatch of finished product, Quality Assurance personnel will issue the Finished Product Release Note (Annexure-II) for getting approval from Head of Quality Assurance. Finish Product Release Note is a self carbonated pre-printed copy as per the original approved copy of Annexure-II
[][]Which contains three different colors Then one carbonated (Yellow colored) copy of the finished product release note will send to central warehouse for distribution. The original blue colored copy will be attached with the batch document.
[][]In case of release of any optimization or validation batch before completion of process validation report, & risk analysis report must be conducted before release. All the documents are approved accordingly by Head of Quality Assurance or his/her designate.
[][]Full batch will be released at a time after completion of the total packaging operation of the batch.
[][]After QA release, Warehouse Executive will store the released product orderly in separated passed area maintaining storage condition. FIFO must be maintained by warehouse executive during dispatch of the released product for distribution.
[][]Quality Assurance Executive will compile all the batch records and kept in the respective Batch Production Record archive area after keeping record in the document archiving log book.
[][]Batch history which must be kept for one year after expiry of the batch.
[][]Fraction batch quantity can only be released with same batch number (while the batch is fractioned as Commercial, Trial Aid or Export) after approval of Head of Quality Assurance.

Batch Release Procedure Read More »

Room Numbering System

Room Numbering , Purpose:

Room Numbering , To provide guidelines for numbering system to all rooms of General Block and Sterile Block in XX Pharmaceuticals Limited.

Room Numbering , Scope:

This procedure is applicable for assigning sequential identification number to all rooms located on each floor of the production, PD/QC/Microbiology area and other area related to Plant operations such as warehouse, plant room, utility area etc are also included in room numbering system.

Definition / Abbreviation:

[][]None

Responsibilities:

[][]The roles and responsibility are as follows:

Executive / Sr. Executive, Engineering

[][]He / she shall be responsible for assigning the sequential identification number to all rooms.

Quality Assurance personnel

[][]He/she shall be responsible for effective implementation and monitoring of procedure.

Quality Assurance Head or Designee

[][]To ensure implementation of SOP.

Procedure:

[][]Numbering for Room
[][]Each room shall be assigned a unique identification number.
[][]Engineering department shall assign floor wise alpha numeric sequential identification Number to all rooms in a logical order on lay out and record the numbering details in Annexure –I.
[][]Do not repeat the same number to another room.
[][]The room numbering shall be a floor wise sequential number having 6 characters as shown below.
=>e.g. GPRXXX
where
=>(G) is the code for General Block
=>(PR) is the working area code for production
=>(XXX) is the first sequential number of room start from 001 to 999
=>Next room shall be numbered GPR002 ……….& so on.

[][]The Building code for each building is given below.

Building name/ Code

=>General Block/G
=>Sterile Block/C
[][]The Working area code for each area is given below.

Area/ Code

=>Production/PR
=>Packaging/PK
=>Warehouse/ WH
=>Product Development/ PD
=>Quality Control/QC
=>Microbiology/MB
=>Mezzanine /ME
=>Roof Top/RT
=>Engineering/EN

Annexure:

Annexure – I: List of rooms

Room Numbering System Read More »

In Process Check (IPC) Procedure

In Process Check, Purpose :

In Process Check, To set up a general guideline for in-process checking that will be followed during the course of manufacturing. This SOP also includes handling of IPC parameters failure during production.

In Process Check, Scope :

This procedure is applicable to all Production activities such as Manufacturing, Packing and warehouse department at XX Pharmaceuticals Limited (Both General and Sterile Block).

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure
[][]QA: Quality Assurance

Responsibilities:

[][]The roles and responsibility is as follows:

Executive, Quality Assurance

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Manager, Quality Assurance

[][]To ensure that this procedure is kept up to date.
[][]To arrange training on the SOP to all concerned personnel.
[][]To ensure implementation of the SOP after training.

Manager, Quality Assurance

[][]Approval of the SOP.

Procedure: In Process Check

General Instruction:

[][]Check the general environment in the department
[][]Ensure proper gowning by the personnel in concerned work area.
[][]Check for the daily calibration of balance.
[][]Check the calibration status label of machines.
[][]Ensure that the line clearance is obtained before starting the next step.
[][]Ensure the destruction of all In-process, rejects, excess overprinted packing material after packing.
[][]Ensure that the every stage of process, appropriate status label is affixed on equipment /machines and containers.
[][]Non Assurance shall be reported immediately to concerned department Head.
[][]Ensure the completion of documentation at the end of each processing stage.

Warehouse Raw Material: In Process Check

=>Ensure line clearance before commencement of dispensing activity.
=>Ensure all the material having properly labeled.
=>Ensure that only “Quarantine” material is stored in quarantine area.
=>Ensure the transfer of Approved material in “Approved Area”.
=>Ensure that storage conditions of raw material are met.

Ensure the following points on Approved Quality Control labels.

=>Analytical Report Number.
=>Re-test date.
=>Ensure that the loose containers are properly closed after dispensing.
=>Ensure that the material is issued on FIFO basis.
=>Ensure that the environmental conditions are maintained in the respective areas.
=>Ensure that the details on dispensed material, material issues slip/dispensing slip are matching with Material Issuance form.

Warehouse Packaging Material:

[][]Ensure proper segregation of materials.
[][]Ensure proper disposal of the rejected items.
[][]Ensure that the material is issued on First In First Out (FIFO) basis.

Warehouse Finished (Drug) Product:

[][]Ensure that the products are dispatched only after QA release.
[][]Ensure the proper storage of goods.
[][]Ensure that “Quarantine” drug product are stored in quarantine area of Warehouse drug product

Parameter for In-process checking during Dispensing:

[][]Area cleanliness, absence of irrelevant/ foreign material.
[][]Equipment cleanliness.
[][]Cleaning record.
[][]Removal of material of previous batch/product from dispensing area.
[][]Balance calibration records, daily accuracy check/ function check of balance.
[][]Status label checking of raw materials prior to weigh.
[][]Weight checking of materials.
[][]Room temperature and Relative Humidity of Dispensing area.

Parameter for In-process checking during Manufacturing:

[][]Generally following parameters shall be checked during manufacturing of tablet/ capsule/ dry powder
[][]Area cleanliness, absence of irrelevant/ foreign material.
[][]Equipment/ machinery cleanliness.
[][]Cleaning record.
[][]Removal of material of previous batch/product from granulation/ compression/ blending/ encapsulation/filling area.
[][]Balance calibration records, daily accuracy check/ function check of balance.
[][]Room temperature and Relative Humidity of the granulation/ compression area (if applicable).
[][]Room display/ product display.

For Tablets:

[][]In Granulation Stage:
[][]Moisture
[][]Temperature (if applicable)
[][]Relative Humidity (if applicable)

In Compression Stage: In Process Check

[][]Appearance (Shape, Surface texture, Physical flaws, Consistency, Identification marking etc.)
[][]Average weight
[][]Uniformity of weight
[][]Relative Standard Deviation
[][]Hardness
[][]Thickness
[][]Diameter
[][]Friability
[][]Room temperature
[][]Relative Humidity (if applicable)
[][]Disintegration time
[][]Machine speed
[][]Organoleptic test (if applicable)

In Coating Stage:

[][]Appearance (Physical flaws)
[][]Average weight
[][]Disintegration time
[][]Weight gain/ coating loss

For Capsules:

[][]In Encapsulation Stage:

[][]Appearance (Color, Size, Identification marking)
[][]Average fill weight
[][]Uniformity of weight
[][]Disintegration time
[][]Relative Humidity of encapsulation room/ area
[][]Temperature of encapsulation room/ area
[][]Locking of capsule

For Powder for Suspension or Syrup:

[][]In Blending Stage:
[][]Relative Humidity of blending/ manufacturing area.
[][]Temperature of blending/ manufacturing area.

In Filling Stage:

[][]Appearance
[][]Relative Humidity of filling room/ area
[][]Temperature of filling room/ area

[][]For Kidney Dialysis Fluid
=>In Manufacturing Stage:
=>Relative Humidity of manufacturing area
=>Temperature of manufacturing area.
[][]In Filling Stage:
=>Uniformity of filling weight
=>pH of solution
=>Conductivity of solution

Checking procedure for IPC during manufacturing:

[][]Room Temperature and Relative Humidity:
[][]Room Temperature and Relative Humidity shall be checked by using Digital Hygrometer and the result shall be recorded in the Batch Manufacturing Record (BMR) in mentioned stage. Room Temperature and Relative Humidity shall be checked as per frequency specified in BMR/BPR.

Moisture:

[][]Moisture shall be checked by using Mettler Toledo balance following corresponding SOP and the result shall be recorded in the Batch Manufacturing Record (BMR) in mentioned stage.

Appearance:

[][]Parameters (as applicable for dosage form type) as mentioned below shall be checked during start-up and in every fifteen (15) minutes interval. About 500 coated tablets from each part shall be checked after completion of coating. Physical flaws of coated tablets shall be recorded in Coated Tablet Visual Inspection Record Sheet.
[][]Color/ Clarity
[][]Shape of tablet
[][]Identification marking
[][]Physical flows in case of capsule

Physical Flaws/ Acceptable Quality Level

[][]Uncoated Tablet
=>Critical Defects (Cracking, Capping/Lamination)/ 0.025%
=>Major Defects (Erosion, Picking/ Sticking)/ 0.25%
=>Minor Defects (Roughness, Illegible logo, Peeling)/ 1.5%
[][]Coated Tablet
=>Critical Defects (Cracking) / 0.025%
=>Major Defects (Blocking, Color Variation, Erosion, Picking/ Sticking) / 0.25%
=>Minor Defects (Twinning, Roughness, Peeling, Core Erosion, Loss of Logo Definition, Logo Bridging ) / 1.5%

The acceptable quality level of physical flaws of coated/ uncoated tablet are as follows:

[][]Weight:

Tablet:

[][]Weight of 05 composite samples, each of which consists of 10/20 tablets shall be checked during start-up and in every fifteen (15) minutes and the result shall comply with the specification as mentioned below:
=>If theoretical tablet weight is ≤80 mg then composite weight shall be in between ±4.0% of theoretical tablet weight.
=>If theoretical tablet weight is >80 mg or <250 mg then composite weight shall be in between ±3.0% of theoretical tablet weight.
=>If the theoretical tablet weight is >250 mg then composite weight shall be in between ±2.5% of theoretical tablet weight.

Capsule:

[][]Composite Fill weight of 10/20 capsules shall be checked during start-up and in every fifteen (15) minutes and the result shall comply with the specification as mentioned below:
=>If fill weight is ≤300 mg then composite fill weight shall be in between ±5.0% of fill weight.
=>If fill weight is >300 mg then composite fill weight shall be in between ±3.0% of fill weight.

Dry powder:

[][]Empty bottle/ plastic container shall be weighted and then tare button of Mettler Toledo balance shall be recorded.
=>After filling with dry powder the filled bottle/ plastic container shall be weighted again to determine the fill weight.
=>Fill weight shall be checked from each filling nozzle. In case of single filling nozzle at least five fill weight shall be checked.
=>The fill weight shall be within the range as specified in BMR. Fill weight shall be checked during start-up and in every thirty (30) minutes interval.

Uniformity of weight: In Process Check

Uniformity weight for tablet and capsule shall be checked during start-up and in every two (2) hours interval.

Tablet:

[][]A number of tablets shall be weighted individually as per the number of punch (if no. of punch is less than 20, then uniformity of weight shall be checked with minimum 20 tablets) of the compression machine. The printed record of statistical data shall be taken and the result of average tablet weight, range of individual weight and % RSD shall be recorded in BMR. The result shall comply with the specification as mentioned below:
[][]Observed average weight shall be within the range calculated with ±2.5 of theoretical tablet weight.
[][]Relative Standard Deviation (RSD) shall be NMT 6.0%.
=>Observed individual tablet weight shall comply with the specification as mentioned below:
=>If tablet weight is ≤80 mg then NMT two tablets shall be outside ±10.0% and none shall be outside ±20.0% range of theoretical tablet weight.
=>If tablet weight is >80 mg or <250 mg then NMT two tablets shall be outside ±7.5% and none shall be outside ±15.0% range of theoretical tablet weight.
=>If tablet weight is ≥250 mg then NMT two tablets shall be outside ±5.0% and none shall be outside ±10.0% range of theoretical tablet weight.

Capsule:

[][]The uniformity of capsule’s fill weight shall be checked by weighing 20 capsules individually. Then the printed record of statistical data shall be taken and the result of average capsule weight shall be recorded in BMR. The result shall comply with the specification as mentioned below:
[][]Observed average capsule fill weight shall be within the range calculated with ±3.0 of theoretical capsule fill weight.
[][]Specification of Relative Standard Deviation (RSD) shall be NMT 6.0%.
Observed individual capsule fill weight shall comply with the specification as described below:
=>If capsule fill weight is ≥300 mg then NMT two shall be outside ±7.5% and none shall be outside ±15.0% range of theoretical capsule fill weight.
=>If capsule fill weight is <300 mg then NMT two shall be outside ±10.0% and none shall be outside ±20.0% range of theoretical capsule fill weight.

Hardness, Thickness and Diameter:

Tablet:

=>Hardness, thickness and diameter of randomly taken 10 tablets shall be checked by ERWEKA TBH 125 machine and a print of found data with statistical evaluation shall be taken and the result shall be recorded in BMR. Hardness, thickness and diameter shall comply with the limit as specified in BMR. Hardness and =>thickness shall be checked during start-up in every one hour interval and diameter shall be checked during start-up.

Disintegration Time: In Process Check

[][]Randomly selected 6 tablets/ capsule shall be placed in 6 different glass tubes of Electrolab ED2 disintegration tester with/without disc (as applicable). The time by which each tablet/ capsule is disintegrated into smaller particles or granules expressed in minutes shall be recorded in BMR. DT of tablet/capsule shall be checked during start-up and every five hours if the batch runs for more than five hours. General guideline for DT of different forms of tablet/ capsule is as follows:
=>Uncoated/ core tablet : NMT. 15 minutes
=>Film coated tablet : NMT. 30 minutes
=>Effervescent tablet : NMT. 5 minutes
=>Hard capsule : NMT. 30 minutes
=>Soft capsule : NMT. 30 minutes
=>Gastro-resistant capsule : 1-2 or 3 hours in acid medium and NMT. 1 hour in buffer medium.

Friability:

[][]Randomly 20 tablets/ 6.5 gm of tablets (for average weight ≤650 mg) or 10 tablets (for average weight >650 mg) shall be selected for friability test. Initially weight of tablets (W1) shall be taken and then be placed in the Friabilator.
[][]The Friabilator shall be run for four minutes at 25 rpm and then tablets of this machine shall be reweighted (W2).Friability of tablets shall be calculated with following formula:

% Friability =W1–W2/ W1×100

[][]A Maximum weight loss NMT 1.0% is considered acceptable for most of the products. Friability of effervescent tablets and chewable tablets may have different specifications.
[][]In case of hygroscopic tablets, an appropriate humidity-controlled environment is required for friability.
[][]Friability shall be checked during start-up and in every two (2) hours interval and be recorded in BMR.

Reconstituted volume for dry powder:

[][]Glassware required for doing the test is 50 ml or 100 ml graduated cylinder.
[][]Water (quantity) shall be taken as specified for the product with a graduated cylinder.
[][]Water shall be poured to the filled bottle and syrup/ suspension shall be made as specified in Leaflet/ Inner carton of the product.
[][]Any observed anomaly (e.g. color, odor, consistency etc.) and the volume with the same cylinder shall be checked.

Parameter for In-Process Checking during packaging:

[][]In case of export besides the following some additional parameters (where applicable) shall be checked like registration no. on foil/label/carton, Text of foil (English/ Bengali), Security overprint on blister/strip etc.

Area:

[][]Room cleanliness
[][]Machine cleanliness
[][]Temperature (0C) [if applicable] [][]% Relative Humidity (if applicable)

Bulk Product:

[][]Product name and strength
[][]Appearance of bulk
[][]Strip/ Blister packing:
[][]General appearance of bulk
[][]Cutting/ perforation
[][]Pocket formation, empty or ruptured pocket
[][]Broken tablets in pocket
[][]Print and color of foils
[][]Color and cleanliness of film (if applicable)
[][]Printing/embossing of Batch No., Mfg. Date and Expiry Date on blister/strip (as applicable)
[][]Improper or inadequate knurling
[][]Sealing (Leak Test)
[][]Camera challenge test (If available on blister machine)

Glass Bottle/ Plastic Container Filling & Packing (Tablets & Capsule):

[][]Appearance of bulk
[][]Quantity per bottle/ container
[][]Cap sealing/ Leak test (as applicable)
[][]Relative Humidity (RH) and Temperature in filling area
[][]Product name with strength on label
[][]Coding Batch no./ Mfg Date/ Exp. Date/ MRP on label (as applicable)
[][]Print and color of label
[][]Security overprint (if applicable)

Inner Cartoning:

[][]Product name and strength
[][]Coding Batch no./ Mfg. Date/ Exp. Date/ MRP (overprinting)
[][]Presence of Leaflet/ Dropper/ Spoon/ Cup/ Cylinder (if applicable)
[][]Adaptability
[][]No. of strip/ blister per pack
[][]Placing of Holographic sticker (if applicable)

Shipping Carton:

[][]Product name and strength
[][]Coding Batch no./ Mfg. Date/ Exp. Date (as applicable)
[][]No. of inner cartons
[][]Serial no.
[][]Size no. and adaptability
[][]Date of cartoning
[][]Signature of the person closing the shipping carton

Checking procedure for IPC during Packaging:

Room Temperature and Relative Humidity:

Room temperature and relative humidity shall be checked as stated above

Leak Test:

[][]At least one sample of conventional strip/ blister/ bottle/ plastic container from each delivery/ cutting channel of the machine shall be picked up from packaging line except sealing machine of one delivery/ cutting channel where two samples shall be collected and checked for integrity following corresponding SOP.
Frequency of Leak test shall be as per following table:

Sample/ Frequency

=>Blister/ Start-up and every hour
=>Empty sealed glass bottles/Start-up and in every hour

[][]If color solution enters into any of the pocket of the strip(s)/blister, into bottle(s)/ plastic container(s) it indicates the leakage.
[][]Calculate the percentage of leakage and record in Leak Test Record Sheet.

Tablet/ Capsule Counting Procedure:

[][]Tablet/ capsule counting procedure shall be performed during start-up and in every 30 minutes.

Annexure: In Process Check

Annexure-I: Coated Tablet Visual Inspection Record Sheet
Annexure-I: Leak Test Record Sheet

In Process Check (IPC) Procedure Read More »

Recall Procedure

Recall, Purpose :

Recall, To ensure recall of products that are known or suspected to be defective or hazardous in accordance with a pre-determined plan promptly and effectively from the market

Recall, Scope :

This procedure is applicable for all products manufactured and distributed from XX Pharmaceuticals Limited (Both General and Sterile Block).

Definitions / Abbreviation:

[][]Recall: A process for withdrawing or removing a pharmaceutical product from the pharmaceutical distribution chain because of defects in the product, complaints of serious adverse reactions to the product and/ or concerns that the product is or may be counterfeit. The recall might be initiated by the manufacturer, wholesale dealer, license holder, or Department of Health.
[][]Market Withdrawal: Market Withdrawal means a firm’s removal or correction of a distributed product which involves a minor violation that would not be subjected to legal action by the Drugs Administration or which involves no violation, e.g., normal stock rotation practices, routine equipment adjustments and repairs etc.
[][]PMD: Product Management Department
[][]QA: Quality Assurance

Responsibilities:

The roles and responsibility is as follows:

Head of PMD

[][]Responsible for determining the intensity of recall to be taken by consultation with Head of QA and taking necessary action.
[][]When product is distributed in domestic/ overseas market, Head of PMD or his authorized nominee shall inform Head of QA for the action to be taken for recall.
[][]Coordinate the recall after obtaining approval from Managing Director.

Manager, Quality Assurance

[][]Approval of the SOP.
[][]To ensure that the implementation of the procedure as per SOP.

Classification of Recall:

[][]Recalls are classified according to the following system
Class I recalls: Occur when products are potentially life-threatening or could cause a serious risk to health.

Examples of Class I Defects

[][]Wrong Product (label and contents are different products)
[][]Correct product but wrong strength, with serious medical consequences
[][]Microbial contamination of sterile injection or ophthalmic product
[][]Chemical contamination with serious medical consequences
[][]Mix up of some products (‘rogues’) with more than one container involved.
[][]Wrong active ingredient in a multi-component product with serious medical consequences

Class II recalls: Occur when product defects could cause illness or mistreatment, but are not Class I.

Examples of Class II Defects

[][]Mislabeling e.g. wrong or missing text or figures
[][]Missing or incorrect information- leaflets or inserts
[][]Microbial contamination of non-injectable, non-ophthalmic sterile product with medical consequences
[][]Chemical/ physical contamination (significant impurities, cross contamination, particulates)
[][]Mix up of products in containers (“rogues”)
[][]Non-Assurance with specification (e.g. assay, stability, fill/ weight or dissolution)
[][]Insecure closure with serious medical consequences (e.g. cytotoxics, child resistant containers, potent products)
Class III recalls: occur when product defects may not pose a significant hazard to health, but withdraw may be initiated for other reasons.

Examples of Class III Defects

[][]Faulty packaging e.g. wrong or missing batch number or expiry date
[][]Faulty closure
[][]Contamination- microbial spoilage, dirt or detritus, particulate matter
[][]Recall system shall be followed in case of Instructions from Regulatory authorities or Voluntary recall by XX authority.

Reason:

=>Reports of adverse reaction.
=>Non-conforming result of on-going stability study.
=>Formulation problem/ Mix-up/ contamination.
=>Labeling errors.
=>Any other reasons.
[][]Head of Quality Assurance shall advise to carry out proper investigation for confirmation of reported defects either jointly or independently by QC, PD, Production & Quality Assurance. PMD personnel can also participate in investigation.
[][]After confirmation and justification of reported defects, Head of Quality Assurance shall discuss with Head of Production and Head of PMD.
[][]Once it is agreed to recall the product(s), Head of Quality Assurance shall seek permission for it from Managing Director (Annexure-III). A Recall Reference no. shall be given on this form as follows:

PR/XX/001
=>Where, ‘PR’ represents Product Recall.
=>‘XX’ represents the last two digits of the year 20XX
=>‘001’ represents for serial number

Recall Panel:

=>Managing Director (MD)
=>Head of Quality Assurance
=>Head of Production
=>Head of PMD
=>Head of Sales
=>Head of Distribution
=>Head of Quality Assurance shall furnish the batch details for recall notification in Annexure-IV. This shall be then forwarded to Head of PMD and Head of sales.

Recall notification shall include:

=>Products name including brand name, its strength and pack size and other details like,
=>Product License (D.A number) if applicable.
=>Batch or Lot number, Batch size, Mfg. date, Exp. date.
=>Nature of defect and reason.
=>Action to be taken (urgent within time frame/ immediate quarantining of stock /return stock) with labeling instruments & specific precautions.
=>Date of  withdrawal.

[][]The Head of PMD through Distribution shall send a product recall circular, immediately upon receiving the product recall decision, to all concerned persons requesting them to return all stock of the batch under question to the depots and informing them that a credit note for the stocks returned shall be issued to them at the earliest.
[][]All product recall requests shall be given top priority unless otherwise indicated by recall coordinator.
[][]The Head of PMD along with Distribution shall immediately arrange to freeze all stocks of the batch lying with distributors, agents and customers. He shall also instruct the entire sales force to freeze further sales of batch at every distribution, sales point (stockiest, chemists, doctors, hospitals etc). This shall also include goods under transit.

[][]In case of recall as per directives of competent or Regulatory Authorities, the information shall be forwarded to them (To include Regulatory Authorities of other Countries to which the batch has been distributed). The decision of disposal of recalled batch shall be as per their directives and the destruction or disposal shall be done under notification and the Drugs Inspector’s supervision.
[][]Quality Assurance Department will record the receipt, origin & quantity of any recalled product received & holds the recalled product in a secure place to avoid mix up with other materials.
[][]The progress  should be reviewed at regular, frequent intervals to monitor its effectiveness and ultimately to decide that the recall is completed.
[][]Completion will normally be reached when:
=>All the acknowledgement forms issued are returned.
=>The material listed in the acknowledgement forms has been returned.
=>There have been no further returns or further adverse reports concerning the product for a period of 2 weeks.
[][]After thorough investigation, Head of Quality Assurance will issue instructions for safe disposal of the recalled stock in due course and a disposal record will be maintained. An investigation into the root cause analysis of any product defect which led to a recall must be carried out and CAPAs to be prepared to prevent if happing again.
[][]Details of recalls shall be added to the batch dossier for all the batches concerned.
[][]Detailed records of all product returned as part of a recall must be kept.
[][]In case of recall when initiated by company (Voluntarily) this shall be informed to the Regulatory Authority.
[][]In case of voluntary recall, product when received back from market to our depots shall be identified and stored separately in a secured area while awaiting a decision on its disposal. The product shall be written off and destroyed as per the standard procedure.

Documentation:

[][]The decisions, activities and actions including progress of recall shall be documented and duly authorized.
[][]On completion of recall procedure, summary report shall be prepared which shall include the following (Annexure V).
[][]Reason for recall of a product (with Batch No. and other details about the product).
[][]Effectiveness of recall.
[][]Corrective action to prevent reason for recall.
[][]Appropriate training to concern as applicable.

[][]This summary report shall be prepared by Head of Quality Assurance and be circulated to all concerned departments (PD, Production, Accounts, Sales, PMD) and Managing Director.
[][]Distribution records should be readily made available to the person(s) responsible for recall and contain sufficient information of wholesalers, retailers, stockiest and customers/agents for prompt and effective it. (Examples: Addresses, Telephone numbers, inside or outside office working hours, batch number and its quantity with them for both domestic and exported products).

Recall Simulation:

[][]The recall procedure shall be regularly reviewed to ensure that it is up-to-date and shall be simulated ‘in house’ to ensure its effectiveness and familiarity to all key personnel.

[][]The required time limit for simulation exercise (from initiation of  simulation to completion) will be not more than 15 days.

Annexure:

Annexure-I: Product Recall Flowchart
Annexure-II: Product Recall Log Book
Annexure-III: Product Recall Form
Annexure-IV: Recall Notification Form
Annexure-V: Summary Report of Recall

Recall Procedure Read More »

Floor Inspection by QA Inspector

Floor Inspection, Purpose :

Floor Inspection, The purpose of this SOP is to describe the roles, responsibilities and activities of production and QC floor inspection and IPCs check by QA personnel and to ensure Assurance with cGMP requirements.

Floor Inspection, Scope :

This procedure is applicable for cGMP observations of production and QC floor at XX Pharmaceuticals Limited (Both General and Sterile Block).

Definitions / Abbreviation:

[][]IPC : In Process Check
[][]QA : Quality Assurance
[][]QC : Quality Control
[][]OOS : Out Of Specification
[][]DT : Disintegration Time

Responsibilities:

[][]The roles and responsibility is as follows:

Quality Assurance Personnel

[][]Responsible for inspection of Production and QC floor to find out any cGMP observations.

Manager, Quality Assurance

[][]To ensure implementation of the procedure

Head of Quality Assurance

[][]Approval of SOP

Procedure:

[][]To assure Assurance with specification throughout a production process, Production Department will conduct the IPC checks following the In-process checks procedure.
[][]IPC inspectors of QA will verify the IPC data independently.
[][]The IPC specification will be mentioned in the relevant product specification and BMR & BPR.
[][]All OOS results will be investigated as per OOS results procedure.
[][]IPC inspector will verify the IPC data based on the frequency described in Annexure–I.
[][]During manufacturing of a batch, production personnel will check the IPC parameters.
[][]If a IPC data goes outside specification, production IPC checking personnel and QA IPC inspector will inform to production Executive for corrective measures.
[][]If QA IPC inspector observes that there is frequent failure of the IPC results then QA IPC inspector will notify the issue to Departmental Manager and Manager, Quality Assurance.

All IPCs will be performed by trained and certified QCOM and Production personnel. Inspection of

=>Adherence to Line clearance
=>Environmental conditions
=>Log books
=>General house keeping
=>Labelling status
=>Sampling
=>Reconciliation
=>Calibration status
=>Deviation
=>Pest controls
=>Cleaning & Contamination
=>Change Control
=>Document management
=>Adherence to maintenance schedule

Inspect GMP compliance in

=>Storage of Raw/Packaging materials/Finished packs
=>Manufacturing/packaging/cleaning operations
=>Dispensing of materials
=>Compliance with SOPs
=>Daily balance monitoring records
QA inspectors will visit the production floor daily. The inspection applies to all operations, specially The following:
=>If any unusual observation comes to the notice of area QA inspector, he will immediately communicate to the Departmental Executive. This report will be recorded in Daily IPC report format (Annexure-II).
=>This inspection report will be forwarded to Manager, Quality Assurance for further action.
=>QA inspectors will collect retention samples of finished packs from the running Secondary packaging line belts & record sampling date and quantity sampled in BPR with sign & date as per Sampling SOP.

In-Process Controls Check:

[][]QA Inspectors will independently conduct all In-process checks in addition to that done by production personnel as Procedure for In-Process Checks.
[][]QA inspectors will conduct the following IPC checks as per frequency described in Annexure–I and as a minimum at least once from every batch of product. This should be done at the start of every batch:

[][]Product: Tablets/Capsule

=>Manufacturing Stage: Encapsulation/ Compression/Coating
=>IPC Checks: Appearance, Average weight, Uniformity of weight, Hardness, Thickness, DT, RH & Temperature
=>Manufacturing Stage: Blister Packing
=>IPC Checks: Leak test, Overprinting, Cutting, RH, Temperature, Product name, Strength, Product code, Mfg & Expiry date, Price and Status label etc.

[][]Product: Powder for Suspension

=>Manufacturing Stage: Manufacturing, Filling & Packing
=>IPC Checks: Appearance, Uniformity of weight, Leak Test, RH, Temperature, Product code, Mfg & Expiry date, Overprinting, Price and Status label etc.

[][]Product: Sterile (Capsules/ Tablets)

=>Manufacturing Stage: Encapsulation/ Compression/Coating
=>IPC Checks: Appearance, Average weight, Uniformity of weight, Hardness, Thickness, DT, RH & Temperature.
=>Manufacturing Stage: Blister Packing
=>IPC Checks: Leak Test, Overprinting, Cutting, RH, Temperature, Product code, Mfg & Expiry date, Price and Status label etc.

[][]Product: Sterile (Powder for Suspension )

=>Manufacturing Stage: Manufacturing, Filling & Packing
=>IPC Checks: Appearance, Uniformity of weight, Leak Test, RH, Temperature, Product code, Mfg. & Expiry date, Overprinting, Price and Status Label etc.

[][]Product: Dialysis Fluid

=>Manufacturing Stage: Manufacturing, Filling & Packing
=>IPC Checks: A Appearance, pH, Weight, Induction Sealing, Cap Sealing, Leak Test, Temperature, Pressure

[][]QA inspectors will verify the IPC results as per specification.
[][]If any batch is completed before inspection of QA IPC inspector, then again QA IPC inspectors will verify the some critical parameters.
[][]In-process test failures must be brought to the attention of the Departmental Executive/ Manager & also Manager, Quality Assurance and appropriate action shall be taken and recorded.
[][]Any problem identified at production floor during printing or in-process checking during packaging, Problem observer immediately inform it, to his/her supervisor and if required Online Problem Notification Form (Annexure-III) to be raised by production through QA.
[][]Reference No. for Online Problem Notification will be as
PN-001/02/XX
Where-
=>PN represents Problem Notification
=>001 represents sequential number
=>02 represent Month of February
=>XX represents year of 20XX

[][]If any receiving quantity of packaging material requires replacement to run production smoothly, it shall be raised by production with Material Replacement Form (Annexure-IV) to warehouse through QA with justified reason for replacement.
[][]Reference No. for Material Replacement will be as
MR-001/02/XX
Where-
=>MR represents Material Replacement
=>001 represents sequential number
=>02 represent Month of February
=>XX represents year of 20XX
[][]The copy of raised Online Problem Notification Form should be sent to Manager, Supply Chain & Management with recommendation of Head of Quality Assurance if required.

QC Floor Inspection:

[][]QA IPC Inspector will also visit the Quality Control laboratory once daily for GLP in place and in use check.

Annexure:

Annexure-I: In-Process Checks
Annexure-II: Daily IPC Finding and Observation Report Sheet
Annexure-III: Online Problem Notification Form
Annexure-IV: Material Replacement Form

Floor Inspection by QA Inspector Read More »

Market Complaint Handling

Market Complaint , Purpose :

Market Complaint , To provide a system for timely response to a product complaint and to make relevant investigation and recommendation with proper documentation.

Market Complaint , Scope :

This procedure is applicable to all types of market complaints received from the market, related to quality, packing and shortage of the products manufactured at XX Pharmaceuticals Limited (Both General and Sterile Block).

Definitions / Abbreviation:

[][]Market Complaint: A written or verbal report originating from customer, retailers, physicians, field supervisor, regional sales coordinator, medical representative, hospitals, regulatory agency and our employees which relates to the inadequacy of the quality, i.e. non Assurance with standards or customer requirements and includes any packaging and labeling requirements, any query regarding specifications, analytical procedure, incomplete text and non conformance with customer requirements should be treated as complaint.
[][]Customer: The person or institution making the complaint.
[][]PMD: Product Management Department.

Responsibilities:

[][]The roles and responsibility is as follows:

Executive/ Manager, PMD

[][]Send the complaints with appropriate details & samples to Manager, Quality Assurance.

Quality Assurance Manager/ designee

[][]Responsible for registering, carrying out the investigation and taking necessary corrective actions, providing necessary technical response to PMD in consultation with General Manager, Plant and Manager, Quality Assurance, generation of the complaint report and closure of the complaint.

Manager, Quality Control

[][]Responsible for carrying out the analysis of samples as per requirement.

Manager, Quality Assurance

[][]Approval of the SOP.
[][]To ensure that the implementation of the procedure as per SOP.

Procedure:

Classification of Complaints:

[][]Market complaints to be classified as minor, major and critical.
[][]Minor: Complaints related to physical appearance of packaging of the product.
[][]Major: Complaints related to physical appearance of the products (e.g. broken tablets, fading, spots etc), packaging quantity (e.g. empty blister, empty bottles, empty content etc), label missing, batch printing missing etc.
[][]Critical: Chemical property complaints related to any chemical test failure of a product, e.g. low purity, change in the impurity level and degradation and shall also include the complaints arising due to stability failure. In the event that a batch is considered to be actually or potentially harmful to user, thereby requiring a recall, following relevant SOP.

Raising of Product Complaint:

[][]Any market complaint received or to be raised by PMD / Sales team shall be filled up in the market complaint form (Annexure-III) along with complaint details (Attach original complaint document to this Annexure if applicable). If the details of the complain are not available in the document then the details of the chemist shop or recipient from where the complaint has been received will be recorded in the market complaint form.
[][]Customer complaints which are received by PMD or complaint raised by PMD will be forwarded to Manager, Quality Assurance with appropriate details in the market complaint form (Annexure- III).
[][]Head of Quality Assurance shall send the complaints along with complaint sample, if received, to Manager, Quality Assurance.
Manager, Quality Assurance shall arrange the investigation and generate a comprehensive report on the market complaints investigation form (Annexure–I).

Investigation of complaints:

[][]Manager, Quality Assurance shall record the complaint in a market compliant logbook (Annexure–II). This detail should include a complaint number, name of the product, batch No., Mfg. date, Expiry date, nature of the complaint, name & address of complainant and date of receipt at the investigating site.
[][]Quality Assurance shall assign a distinct control number to every complaint as follows:
MC/XX/001
Where,
MC – Market Complaint.
‘XX’ represents the last two digits of the year 20XX
‘001’ represents for serial number of the market compliant on continuous basis starting from
001 for the calendar year.
[][]If complaint sample is received along with the market complaint, the investigator shall record the quantity of sample received in the market complaint investigation form (Annexure–I).
[][]If no complaint sample is received along with the complaint, the investigator shall record the relevant details disclosed in the complaint form.
[][]Quality Assurance Manager shall carry out the detailed investigation of the market complaint under the supervision of Head of Quality Assurance to find out the root cause of the complaint and to generate corrective & preventive actions. In his/her absence, Head of Quality Assurance shall nominate any other person to carryout activities in this regard.
[][]Investigator shall carefully inspect and record the physical appearance of the sample, seal etc. and compare the details of the references available in documents of the same batch number. Chemical analysis shall be done on the sample at this point of time.
[][]The investigator in consultation with Head of Quality Assurance shall arrange to carry out chemical and / or microbiological analysis of the reference sample (along with the complaint sample, if available). The investigator must also scrutinize the analytical report of the product under reference.
[][]The investigator shall then discuss the results of the analysis with General Manager, Plant for the investigation at production end.
[][]General Manager, Plant along with the respective departmental manager shall investigate the complaint in details.
[][]The investigation should include scrutiny of batch production records for any manufacturing and/or packing problems encountered during the production of the batch.
[][]Any equipment breakdowns recorded during production of the batch and any material quality problems faced during manufacturing and packing of the batch also must be studied.
[][]In case of following nature of the market complaints, AGM, Quality Assurance in consultation with Managing Director may decide to recall the product / batch as per Recall procedure.
[][]Product mix up and label mix up
[][]Failure to meet regulatory specification (i.e. Assay, impurity)
[][]Adverse drug reaction due to product defect.
[][]Contamination due to foreign matter. (e.g. Glass pieces, metal pieces, black particles, particulate matter, microbial growth etc.)

[][]The closure of complaints along with redressal should be completed within 1(one) month period after the receipt of the complaints. Any delays shall be justified.

Product Complaint Redressal:

[][]Head of Strategic Marketing and Communication after consultation with Managing Director shall appraise the customer on the corrective actions taken and on the redressal actions, wherever necessary and a copy of such shall be forwarded to Head of Quality Assurance for his/her reference.
[][]Management Reviews of Complaints:
[][]The product complaint report, the trends, effectiveness of the corrective actions etc. shall be summarized and reviewed in management review meeting.

Annexure:

Annexure-I: Market Complaint Investigation Form
Annexure-II: Market Complaint Log Book
Annexure-III: Market Complaint Form
Annexure-IV: Flow Diagram For Handling of Market Complaints

Market Complaint Handling Read More »

Leak Test Apparatus Operation, Calibration and Cleaning

Leak Test Apparatus , Purpose :

Leak Test Apparatus , The purpose of this SOP (Standard Operating Procedure) is to describe the operation, calibration and cleaning of leak test apparatus.

Leak Test Apparatus , Scope :

This procedure is applicable for leak test apparatus (Model: Electrolab, LT-101P ) used in the In Process Check of General Block at XX Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A

Responsibilities:

[][]The roles and responsibility is as follows:

Executive, Quality Assurance

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Asst. Manager, Quality Assurance

[][]To ensure that this procedure is kept up to date.
[][]To arrange training on the SOP to all concerned personnel.
[][]To ensure implementation of the SOP after training.

Manager, Quality Assurance

[][]Approval of the SOP.

Procedure:

Precaution(s):

[][]Laboratory coat must be worn while handling the instrument.
[][]Disconnect the power supply before moving or cleaning of the instrument.
[][]Prior to use, user must ensure that equipment is calibrated.
[][]Preparation of Rhodamine B Dye Solution:
[][]Prepare a 2 liters solution of Rhodamine B dye by dissolving 0.5 gm of the dye in water. Take 800 ml water in a 1000 ml beaker and make it colored by adding about 5 ml of the dye solution.

Operating Procedure:

[][]Place the sample in the desiccators which is filled with Rodamin solution to the desired level.
[][]Connect the vacuum tubing between desiccators and the Vacuum Inlet Nozzle provided on the back panel of the instrument.
[][]Switch ON the power switch, then LCD screen displays LEAK TEST APPARATUS followed by SERIAL NUMBER of the instrument and changes over to Vacuum in mm, Hg and Time.
[][]Press the SET key to change to vacuum and input required data by using UP, DOWN and SHIFT keys.
[][]To change HOLD TIME press the SET key and input required data by using UP, DOWN and SHIFT keys.

[][]To show USER ID on screen, press SET key. To setup USER ID press UP or DOWN key.
[][]To change SAMPLE ID press the SET key and input required data by using UP, DOWN and SHIFT keys.
[][]To change No. of samples press the SET key and input required data by using UP, DOWN and SHIFT keys
[][]To change BATCH NO. press the SET key and input required data by using UP, DOWN and SHIFT keys.
[][]After all the data is entered, press the ENTER key and then press the RUN key to run the program which is set for required test. Then vacuum release takes place for three seconds and the pump starts and the vacuum built up which is displayed on the LCD screen. If no vacuum builds up then press desiccator top lid for a few seconds.
[][]When vacuum release reaches zero place automatically then press the print key to get full details of the test.
[][]Leak test parameters

Type of product/Pressure/Time

[][]Tablet, Capsule, Vial/450 mm-hg/5 minutes
[][]Powder for Suspension/450 mm-hg/2 minutes

Procedure for setup time, date and serial number:

[][]Switch ON the instrument and press up arrow key until hear a buzzer sound, then shows password.
[][]Enter password.
[][]The password is four digit 8824 and press enter key.
[][]Date format is 2013 02 16 (Year Month Day) and Time format is 12:15(Hours, Minutes).
[][]Input necessary data by using up, down and right shift key, Date and time can be changed.
[][]To show Serial No. on screen press Enter key
[][]Input necessary data by using up, down and right shift key, Serial No. can be changed.
[][]When all data is entered completing then press Enter key.
[][]Switch OFF the instrument.
[][]Switch ON the instrument after few minutes and check the above recorded data and verify.

Calibration procedure:

[][]Calibrated stopwatch and start timer of leak test apparatus and stop watch simultaneously.
[][]Note the reading at intervals of 60 seconds, 180 seconds and 300 seconds respectively.
[][]Acceptance criteria: 10 seconds for each interval.
[][]Vacuum gauge calibration done by external party.
[][]Frequency of calibration: Twelve months (for timer, vacuum gauge and vacuum holding capacity).

Cleaning procedure:

[][]After completion of the testing, switch off the instrument.
[][]Cleaning of leak test apparatus by using purified water and clean outer and inner surface with the help of lint free cloth.
[][]Place the apparatus for dryness for half an hour.
[][]Change the desiccator Rodamin solution twice in a week or as per required.

Annexure:

Annexure-I: Log Book of Leak Test Apparatus.

Leak Test Apparatus Operation, Calibration and Cleaning Read More »

Training Procedure

Training Procedure, Purpose:

Training Procedure, To lay down guidelines for training of new entrants and periodic retraining of technical staff.

Training Procedure, Scope:

[][]This procedure is applicable for all employees of General block and Sterile block at XX Pharmaceuticals Ltd. for
[][]On the job training (OJT)
[][]Class room training (CT)
[][]External training
[][]Basic GMP training

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.

Responsibilities:

[][]The roles and responsibility is as follows:

Executive, HR & Admin.

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.
[][]To check the records of training filled by trainee.
[][]To maintain employ training record.
[][]To prepare list of training given to the employees.
[][]To file all records of training in their individual training file.
[][]Training is given in all departments as per the induction form.

Manager, Human Resources

[][]To preserve all training record
[][]To co-ordinate in all training program

General Manager, Plant

[][]To ensure that this procedure is kept up to date.
[][]To ensure implementation of the training as per SOP.
[][]To assess the training requirement.

Manager, Quality Assurance

[][]Approval of the SOP.

Procedure:

[][]The manufacturer should provide training for all the personnel whose duties take them into production areas or into the control laboratories (including the technical, maintenance and cleaning personnel) and for other personnel whose activities could affect the quality of the product.

New Entrants:

New entrants to the organization shall be given induction training and brief cGMP/GLP training by Head of Quality assurance or Quality Assurance within 10 days of joining.
[][]New entrants should be given technical training (need based) by the departmental manager depending upon the nature of job for one month.
[][]New entrant should be instructed to observe the activity in the recruited department for one month after the initial induction program.
[][]A written feedback is collected from new entrants after the training to ascertain his/her competence in both technical and cGMP skills.
[][]Quality Assurance shall prepare a regular annual schedule for training/retraining of technical staff.
[][]The Qualified trainer who has conducted the training should review and assess the feedback.
[][]Based on the assessment, trainer shall identify training retraining needs.
[][]Individual Training record should be maintained for each new entrant along with their feedback.
[][]Once the induction is over the new employees hand over induction training format duly filled with all required signatures to HR & Admin. Department.

Classroom training:

[][]Prepare the training schedule and circulate to all Department Heads for information.
[][]Upon finalization of training schedule, intimate to participants.
[][]Prepare required training aids and conduct the training program.
[][]On completion of the training, evaluate the training imparted by giving a questionnaire. Trainer is required to set the questionnaire.
[][]Trainer evaluates the answer & ranks them as Excellent (>90%), Very good (>80-90%), Good (>60-80%), Poor (<50%).
[][]Poor performers are retrained and re-examined.
[][]After training, trainer provides “Individual Training Record” to the trainee for getting feedback.

[][]All trainees fill the same immediately after the program gets over & submit it to the trainer.
[][]Trainer notes the contents, signs each reports & forward the same to HR & Admin. Department who keep all training related records.
[][]Maintain the training record in training file and update the Employee training card.

On-the-job training:

[][]On need base a competent person organizes on job training to concerned persons either individually or in small group preferably of 5 to 7.
[][]Trainer first explains the theoretical aspects making use of writing boards/printed literature diagram etc.
[][]Explain or demonstrate the actual operation or system to participant.
[][]Training record is maintained in the form as explained above.

External training:

[][]Upon information from various agencies nominate the person on consultation with department head.
[][]Make the necessary arrangement like tickets, hotel arrangement etc. to attend the external training.
[][]After training, trainee will submit the report in the prescribed format as per Annexure- V, to HR & Admin. Department through Department Head. Brief [][]information about the program need to be enclosed with the report.
[][]Maintain the training record in training file and update the Employee training card of concerned employees who have undergone external training as per SOP.
[][]Trainee shares the literature & knowledge gained in the program with all this colleagues.
[][]Department Head may ask the concerned employee to make a presentation on the topic concerned for the benefit of all those concerned who were not sent for training.

Training on basic GMP practice:

[][]Department Head training the new comer on following points:

Production :

[][]Importance of good manufacturing practices and requirements.
[][]Systems related to manufacturing.
[][]System related to packaging (printed and unprinted component code etc).
[][]Documentation.

Warehouse:

[][]General warehousing procedure.
[][]Function carried out by Warehouse.
[][]Document related to warehouse.

Engineering:

[][]Facilities and services
[][]Brief working of the services
[][]Documentation

Quality Assurance:

[][]General information on SOP, GMP Documentation.
[][]Activities of Quality Assurance, Product Development, Microbiology & Quality Control.
[][]Product information.
[][]Other specific activity related to the employees department.

Training schedule:

[][]New entrant: General factory rules and cGMP –10days
[][]Regular training for staff and operators
[][]cGMP – Once in 6 months
[][]GLP – Once in 6 months
[][]Technical training – Once in 3 months
[][]A training session by an External Agency shall be conducted as and need/opportunity arises.
[][]Apart from the schedule, training/retraining sessions will be conducted as and when need arises.

Annexure:

Annexure-I: Individual Training Record.
Annexure-II: Training Log.
Annexure-II: Induction Training Format.
Annexure-IV: Employee Training Card.
Annexure-V: Training Program Report.

Training Procedure Read More »

Manufacturing & Expiration Date Assigning of Products

Manufacturing & Expiration Date, Purpose :

Manufacturing & Expiration Date, The purpose of this SOP (Standard Operating Procedure) is to provide a system for assigning of manufacturing & expiration date of products manufactured in XX Pharmaceuticals Limited.

Manufacturing & Expiration Date, Scope :

All departments of XX Pharmaceuticals Limited (Both General and Sterile Block).

Definitions/Abbreviation:

[][]BMR : Batch Manufacturing Record
[][]BPR : Batch Packaging Record
[][]LPL : XX Pharmaceuticals Limited
[][]MFG. : Manufacturing Date
[][]EXP. : Expiry Date
[][]VAT : Value Added Tax
[][]IP : Indicating Price

Responsibilities:

[][]The roles and responsibility is as follows:

Executive, Quality Assurance

[][]To ensure that this procedure is followed.

Executive, Production

[][]To follow laid down procedure.

Manager, Quality Assurance

[][]To ensure implementation of the SOP.

Head of Quality Assurance

[][]Approval of the SOP.

Annexure:

N/A

Procedure:

Assigning of Manufacturing Date
[][]Determine the manufacturing date of a batch from the month and year at which manufacturing of that batch starts (i.e. dispensing). Consider the BMR issue date as starting point of a batch. So the month and year of issuing BMR will consider as manufacturing date.
[][]First 3 (three) letters of month and last 2 (two) numerical digits of year representing the manufacturing date.
[][]Assign the manufacturing date in block letters.
Assigning of Expiry Date
[][]Determine the expiry date from the manufacturing date and claimed shelf life of the product.
[][]First 3 (three) letters of month and last 2 (two) numerical digits of year representing the expiration date.

[][]Those products which have no manufacturing steps except encapsulation / filling, expiry date will be declared as the manufacturer’s claimed expiry date of the active material (i.e. pellets, ready granules, different materials for injectable etc.).
[][]When the active material of two different Lab. Control No. will use in one batch, then the expiry date of the product should be considered as like shorter expiry date of API claimed by the manufacturer.
[][]Assign the expiry date in block letters.
Example: a) When claimed shelf life is 1 years.
[][]For example: Cerolab 10 Tablet
[][]If manufacturing starts (or BMR issue) at January .
[][]The manufacturing date is JAN  and expiry date is DEC of the following year
b) When claimed shelf life is 1.5 (One and half) years.
[][]For example: Cerporal PFS, 50 ml
[][]If manufacturing starts (or BMR issue) at January
[][]The manufacturing date is JAN  and the expiry date is JUN of the following year

[][]Batch number, manufacturing date, expiry date and indicating price should be printed in different packaging material as following procedure:
For inner carton (if product shelf life is 1 year)
BATCH NO. : XX0001
MFG. DATE : JAN XX
EXP. DATE : DEC XX
IP (with VAT) :

Manufacturing & Expiration Date Assigning of Products Read More »

Qualification Procedure

Qualification ,Purpose :

Qualification , The purpose of this SOP (Standard Operating Procedure) is to provide guidelines for carrying out the qualification at the site.

Qualification , Scope :

This SOP is applicable for qualification of all equipment, instrument, facility and utility at the site of General Block and Sterile Block of XX Pharmaceutical Ltd.

Definitions / Abbreviation:

[][]Qualification: The action of proving and documenting that equipment or utility are properly installed, work correctly, and actually produce the expected results.
[][]User Requirement Specification (URS): Documented requirement of the equipment, utility for its intended purpose. Functional design and specification according to cGMP and regulatory requirements.
[][]Design Qualification (DQ): Documented verification that the proposed design of the equipment, utility is suitable for the intended purpose.
[][]Installation Qualification (IQ): Documented verification that the equipment, utility as installed or modified, comply with the approved design, manufacturer’s recommendations and user requirement. FAT& SAT to be added.
[][]Performance Qualification (PQ): Documented verification that the equipment, utility is performing effectively and reproducibly, based on approved method and specifications.
[][]Factory Acceptance Test (FAT): Documented verification of the equipment at vendor’s site against approved design.
[][]Site Acceptable Test (SAT): Documented verification of the equipment at user site against approved design.
[][]HVAC: Heating, Ventilation & Air Conditioning
[][]LAF: Laminar Air Flow

Responsibilities:

[][]The roles and responsibility is as follows:

User department

[][]To prepare the URS of equipments, instruments, facility, utility.
[][]To prepare DQ (if required).
[][]To prepare PQ protocols

Validation Team

[][]He I She shall be responsible to carry out this procedure as defined

Engineering Department

[][]To prepare IQ, OQ protocols whenever required.
[][]To provide technical assistance to the user department for preparation of require documents.
[][]To prepare protocols for facility and utility in co- ordination with user department

Quality Assurance

[][]To review protocols and to provide technical inputs
[][]To review  reports for its completeness and correctness all data and report.

Head of Engineering

[][]He I She shall Be Responsible for Effective Implementation of this Procedure.

Head of Plant

[][]He I She shall Be Responsible for Effective Implementation of this procedure.

Head of Quality Assurance

[][]He/ She shall be responsible for effective implementation of this procedure.
[][]To approve protocols, reports and master plan.
[][]Approval of the SOP.

External agency

To provide technical assistance for preparation of documents and execution of activities whenever required

Procedure:

Methodology

[][]Facilities, Utilities and Equipment’s used for manufacturing, processing, packaging, labeling, storing, testing and controlling of drug products shall be qualified prior to use.
[][] It shall be performed for new equipment /instruments/utility/facility, after major breakdown in equipment/utility, after modification in equipment/instrument/utility and facility.
[][]Re-qualification shall be performed at define frequency.

Introduction of a new equipment/ facility/ utility:

[][]After receiving the new Equipment Engineering shall make entry in respective format and Concern
[][]department shall update the Equipment Master List as per respective of SOP.
[][]Equipment no. shall be assigned as per the SOP for Equipment and Instrument Numbering System.
[][]For new equipment following activities shall be done to demonstrate conformance to design documents, characteristics, and capabilities specified in required documents.
[][]User requirement specification (URS)
[][]Design qualification(DQ)
[][]Factory Acceptance Tests (FAT)
[][]Site Acceptance Test (SAT)
[][]Installation Qualification(IQ)
[][]Operation qualification(OQ)
[][]Performance Qualification(PQ)

User Requirement Specification:

[][]The URS is made to verify that the owner/user requirement, which includes establishment of critical operating or operational parameters or specifications before the final design agreed, has been met.
[][]User shall prepare the URS considering all operational, safety and GMP requirements.
[][]The user requirement shall be submitted to manufacturer/supplier, based on which manufacturer/supplier will prepare design.

DQ:

[][]The DQ is made to verify that the owner/user requirement, which include establishment of critical operating or operational parameters or specifications before the final design is agreed, has been met.
[][]Based on URS, manufacturer/supplier shall prepare design it documents and submit to user for approval.
[][]On the basis of approved design it documents, manufacturer /supplier shall start manufacturing/fabricating the equipment/utility.

Factory Acceptance Test:

[][]The FAT is prepared to verify that the main items or system meets design specification and conforms to agreed performance intent.
[][]User shall prepare FAT protocol according to URS/DQ, manufacturer specification and purchase order User shall ensure that the equipment/system is manufactured as per designed specification at manufacturer’s site.
[][]User also check the basic performance of the equipment/ system delivered at plant meets the design specification.
[][]User shall take photocopy of the approved FAT protocol and execute at the manufacturer’s site with QA and Engineering representative.
[][]All the test shall be performed and reported by the supplier. All tests performed during FAT must be performed in accordance with reviewed and and approved protocol and procedure.

Site Acceptance Test:

[][]The SAT is to establish documented evidence that the receipt of the item at site confirms with the standards laid down in the protocol, FAT, purchase order and manufacturer’s specification.
[][]User shall prepare SAT protocol according to the manufacturer specification, purchase order and FAT report.
[][]User shall take photocopy of the approved SAT protocol and will check the entire test mentioned in protocol with the QA & Engineering representative at the site when item I equipment I system reaches to the factory premises and reported by the production and engineer.

Installation Qualification:

[][]Installation Qualification of Equipment/utility shall be carried out is to ensure that the equipment I utility is installed according to design documents, purchase. Specifications, FAT and SAT report and planned modification.
[][]The parts of the systems, which are disassembled prior to shipping, shall be noted and be verified again after re-assembly at the final site during IQ.
[][]Equipment/utility shall be inspected either visually or by measurement for its critical parts. Wherever applicable other instruments shall be used for this purpose.
[][]All the relevant tests mentioned in protocol shall be checked after proper installation of equipment. Calibration of instrument attached with equipment and other related shall carried out before starting OQ.
[][]After completion of IQ the equipment shall be released OQ.

Operation Qualification:

[][]The Operational Qualification is carried out to verify that an Equipment/system or subsystem performs as intended throughout all anticipated operating ranges.
[][]Operation qualification activities shall start only after completion of successful IQ.
[][]QA and User representative shall use photocopy of approved protocol, which is used earlier during IQ.
[][]User department shall verify proper operation by performing the critical operating parameters that have significant impact on the equipment ability to operate and meet specifications satisfactory.
[][]User department shall prepared final conclusion after the test functions are checked and observed within specification.
[][]After completion of OQ the equipment shall be released either for PQ or for routine use as the case may be.

Performance Qualification:

[][]The performance qualification is carried out to provide documented evidence that an integrated system or processing operation is capable of performing consistently (during multiple cycles or extended periods) to give an outcome that meets predetermined specifications.
[][]PQ activities shall start only after completion of successful OQ.
[][]PQ of equipment depends upon equipment intended use and its operation.
[][]Data shall be generated to establish that the equipment meets the requirement as expected of it.
[][]A final report shall be prepared, summarizing the results obtained, commenting on any deviation observed and final conclusion shall be given after the PQ.
[][]PQ can be performed on commercial batches for new equipment. The batches shall be released only after the qualification of the equipment is completed or can be performed on placebo /dummy / trials wherever applicable.
[][]PQ shall be performed for consecutive three batches/trials with load.
[][]After completion of execution, all raw data and reports shall be compiled and a final conclusion shall be drawn.
[][]After final approval of conclusion/report by plant head and quality head the respective equipment, instrument, facility and utility shall be allowed for routine use.

Note: Operation and PQ shall be carried only if desired utility is available and environmental conditions (wherever applicable) are achieved in the area.
Qualification for introduction of a new Instrument:

[][]For new Instrument following activities shall be done to demonstrate conformance to design documents, characteristics, and capabilities specified in requirements documents.
=>Installation Qualification (IQ)
=>Operation qualification (OQ)
=>Performance Qualification (PQ)

[][]IQ : for new Instrument shall be carried out as per procedure mention above.
[][]OQ : OQ for new Instrument shall be carried out as per procedure mention above.
[][]PQ : OQ for new Instrument shall be carried out as per procedure mention above.

Protocol Preparation for FAT, SAT, IQ, OQ and PQ:

[][]The protocol for Qualification (FAT/SAT/ IQ / OQ / PQ) shall address and include, but not necessarily be limited, to the following topics.
[][]FAT: Approval, purpose, procedure, verification criteria, Manufacturer’s Machine Identification Code / Identification No., Final report approval.
[][]SAT: Approval, purpose, procedure, Documentation, Verification criteria, Final report approval.
[][]IQ/OQ/PQ: Purpose, Scope, Responsibility, Intended Use, Location, Reference, History, Attachments, Study for qualification, Responsibilities, Signature log, Training record.
[][]IQ : Equipment/Instrument Detail, Procedure, IQ table, Conclusion.
[][]OQ : SOP training, Procedure, OQ table, Observed deviation, Conclusion.
[][]PQ: Procedure, Acceptance criteria, Observed deviation, Final Conclusion Report approval sheet.
[][]Specimen of Header and Footer for above protocol is as per given below.

At the Header Section

1st Column: Company Logo
2nd Column: Company Name, Address Details
3rd Column: Doc. Title, Document No., & Location

Specimen of Footer on all Page

CONFIDENTIAL TECHNICAL DOCUMENT

[][]Numbering and Issuance system for Qualification protocol shall be as per SOP for Document numbering system.

Area Qualification:

[][]Area Qualification is carried out to provide the documentary evidences that particular area is constructed and qualified as per predefined specification.
[][]Below mentioned activities shall be performed during execution of Area Qualification, but not limited to.
[][]Construction and finishing of wall, floor, doors, view panels and ceiling.
[][]Dimension measurement wherever applicable.
[][]All the required utilities and other facilities supplied.

[][]Lighting lux of every room in all four corners and center of the room.
[][]Temperature Mapping for Classified area.
[][]Environmental condition monitoring for classified area.
[][]Water drains ability of drains.
[][]Cleaning and Sanitization Procedure.
[][]User department shall prepare the qualification protocol and organize the qualification study in co- ordination with Quality Assurance and Engineering department.
[][]Protocol/Report shall be finally reviewed by Multidisciplinary authorized personnel along with QA personnel and approved by Quality Head.

[][]Specimen of Header and Footer for above protocol is as mentioned above.
[][]Numbering and Issuance system for Qualification protocol shall be as per SOP for Document numbering system.

Qualification of HVAC system:

[][]HVAC qualification shall be carried out to supply the required air quality to the various section of individual department to provide product protection from air borne contamination, to maintain the temperature and humidity, to provide differential room pressure or air flow movement to provide product protection from cross – contamination.
[][]All HVAC system like AHU’s shall be qualified as per procedure described above as per approved protocols.
[][]Engineering department shall prepare the qualification protocol and organize the qualification study in co-ordination with Quality Assurance.
[][]Engineering person shall record the observations as per designed protocol and prepare a report.
[][]Below mentioned test shall be performed during qualification of AHU, but not limited to.

DOP or PAO Test
Air velocity & Air changes Test
Non viable particle count
Filter efficiency & integrity.
Particle count Test.
Microbial Count.
Air Flow Direction & Air Flow Pattern
Recovery Study
Protocol/Report shall be finally reviewed by QA and approved by Head of QA.
Specimen of Header and Footer for above protocol is as mentioned above.

[][]Numbering and Issuance system for Qualification protocol shall be as per SOP for Document
numbering system.

Qualification of LAF:

[][]Qualification of LAF shall be carried out to provide the air with high-pressure compare to surrounding area and to prevent microbial and particulate matters contamination during dispensing/sampling of Raw material, prevent dusting during dispensing/Sampling.
[][]All LAF shall be qualified as per procedures described  as per approved protocol.
[][]User department shall prepared the qualification protocol and organize the qualification study in co-ordination with QA & Engineering department.
[][]Numbering and Issuance system for Qualification protocol shall be as per SOP for Document numbering system.

[][]Installation Qualification: IQ of LAF shall be carried out to check LAF size as per requirement, to check pre-filter, motor blower, Magnehelic gauge and final HEPA filter as per specification.
[][]Operational Qualification: OQ of LAF shall be carried out to run the LAF and to check the operational parameter functioning.
[][]Performance Qualification: PQ of LAF shall be carried out to check LAF air velocity, Air flow pattern, air cleanliness by non viable particle count and HEPA filter efficiency & integrity, etc.
[][]User department shall record the observations as per designed protocol and prepared a report.
[][]Protocol/Report shall be finally reviewed by QA and approved by Head of QA.

Qualification of Water System:

[][]Water system qualification shall be carried out to generate Potable water & purified water of desired quality.
[][]Engineering department shall prepared the qualification protocol and organize the qualification study in co-ordination with QA.
[][]Qualification protocol shall carried following details but not limited to, IQ: Equipment/instrument details, procedure, Acceptance criteria, Pre-
qualification, Installation check, summary & conclusion.
[][]OQ: Training, Procedure, Acceptance criteria, operating inputs, summary & conclusion.
[][]PQ: Study plan, sampling Frequency, user point, summary & report.
[][]PQ of water system shall be carried out in a two phase.
[][]In phase 1, water quality parameter trend shall be evaluated on monthly basis.
[][]In phase 2, water quality parameter trend shall be evaluated after one year to evaluate impact of seasonal changes on quality of water.
[][]Engineering department shall record the observations as per designed protocol and prepared a report.
[][]Protocol/Report shall be finally reviewed by QA and approved Head of QA.
[][]Numbering and Issuance system for Qualification protocol shall be as per SOP for Document numbering system.

Re-qualification strategy:

[][]Equipment futility shall be re-qualified either in following conditions:
[][]Major Break Down.
[][]After modification in equipment, utility, facility which may have an impact on product quality only.
[][]Design change of spares that have impact on the performance of equipment and quality of product.
[][]In case of during Location change of equipment. (In case of balances only recalibration shall be done).
[][]As per scheduled re-qualification of critical and non equipment/utility.
[][]OQ & PQ shall be performed during requalification.
[][]PQ shall be performed with one batch during requalification.

Re-qualification criteria for critical equipment:

[][]Operational and performance qualification shall be done as per approved protocol for re-qualification of critical equipment.
[][]All critical equipments shall be re-qualified after every three years ± 1 month.
[][]During re-qualification of critical equipment/utility, only 00 and PO shall be performed. PO shall be conducted with one batch only.

[][]Re-qualification criteria for non critical equipment.
[][]Re-qualification of non critical equipment shall be conducted whether there is significant change that has influence on quality of product.
[][]For re-qualification of non-critical equipment, history of maintenance and utilization of the equipment shall be reviewed and documented as per format of Re qualification of non-critical Equipments (Attachment 1).
[][]All non – critical equipments shall be re-qualified after every three years ± 6 months.

Re-qualification criteria for Instrument in following conditions:

[][]When the instrument is shifted from one laboratory (Change in premises) to another laboratory, re qualification (10, 00 and PO) is required.
[][]When the instrument is upgraded or after having a major repairing, qualification (OO/PO) is required.
[][]When the instrument is shifted within the laboratory premises (one room to another room), re qualification is not required, in house calibration is required.

Re-qualification criteria for HVAC System:

[][]Re qualification of HVAC(AHU) shall be carried out in below mention criteria, but not limited to Change in a location of the equipment/system.
[][]Major change in equipment, Change of spare/ parts that have a direct bearing on the Performance of the equipment.
[][]Schedule Re-Qualification.
[][]Frequency of Re-qualification of AHU shall be One Year.± One month. Below mentioned test shall be carried out at defined frequency.

Parameter/Frequency

=>Air Velocity /Initially and Once in year
=>Air Changes /Initially and Once in year
=>Filter Integrity Test /Initially and Once in year
=>Particle Count /Initially and Once in year
=>Microbial Count /Initially and Once in year
=>Air Flow Direction /Initially and Once in year
=>Air Flow Pattern /Initially and Once in year
=>Recovery Study /Initially and Once in year

Re-qualification criteria for LAF:

[][]Re qualification of LAF shall be carried out in below mention criteria, but not limited to.
[][]Change in a location of the equipment/system.
[][]Major change in equipment, Change of spare/ parts that have a direct bearing on the Performance of the equipment.
[][]Critical gauges shall be replaced or corrected if the gauge is found out of calibration during calibration of the gauges.
[][]Schedule Re qualification.
[][]Frequency of Re-Qualification of LAF shall One Year.± One month.

Re-qualification criteria for utilities:

[][]Re-qualification shall be carried out to ensure that change I modification in utilities remain under
[][]Control and within the parameters defined and certified.
[][]Re qualification of utilities shall be carried out in below mention criteria, but not limited to.
[][]Change in location

[][]Any modification that has a potential to impact the product quality.
[][]Scheduled re-qualification after every 3 years.

Re-Qualification of Compressed Air:

[][]Re qualification of Compressed Air shall be carried out in below mention criteria, but not limited to,
[][]In case of any modification which has impact on product quality.
[][]Scheduled re-qualification after everyone year.

Annexure:

Annexure-I: Requalification of non-critical Equipment’s

Qualification Procedure Read More »

CAPA Procedure

CAPA, Purpose:

CAPA, The purpose of this document is to define a systemic, standardized and effective approach to ensure that a system is in place to address quality and compliance issues and to continually improve operations by identifying any required remedial, corrective and preventive actions and implement them in a controlled fashion.

CAPA, Scope:

The process applies to quality related non-conformities or undesirable situations in XX Pharmaceuticals Ltd. (Both General & Sterile Block) from any one of the following interface processes where CAPA is required to prevent recurrence or potential occurrence of the :
[][]Critical or major deviation.
[][]Critical or major justified market complaints.
[][]Outcomes of change control procedure
[][]Internal audit
[][]Risk Management
[][]Product incidents and recall
[][]Batch rejects and reworks
[][]Periodic product reviews
[][]Stability Test Failure
[][]Out of specification results investigations.
[][]Output of monthly quality review meeting
[][]Any other investigation
[][]The process does not apply to the following as these are managed separately by individual SOPs:
[][]Minor deviation.
[][]Triggered from various gap analysis

Definitions / Abbreviation:

[][]QA: Quality Assurance
[][]SOP: Standard Operating Procedure
[][]CAPA: Corrective action and preventive action
[][]Remedial action: Action to eliminate the immediate compliance issue associated with a deviation or non conformance.
[][]Corrective action: Action to eliminate the cause of a detected non conformity or other undesirable situation & avoid reoccurrence.
[][]Preventive action: Action to eliminate the cause of a potential non conformity or any undesirable potential non conformity & avoid occurrence.

Responsibilities:

The roles and responsibility is as follows:

Head of Quality Assurance or his/her Designee

[][]Provide effective governance of the CAPA process
[][]Ensure local process are managed according to SOP
[][]Post approved CAPA in CAPA tracking system and update it
[][]Follow up and verify close-out
[][]To authorize the closure CAPA’s

Functional Head or his designee

[][]To approve and ensure implementation of the solution into routine use

CAPA owner

[][]Accountable for CAPA objective
[][]To assess possible impact on other functions
[][]Nominate CAPA leader
[][]To approve implementation of the solution into routine use.
[][]To implement the CAPA into routine use
[][]To collect data for long term monitoring of the CAPA

CAPA Team

[][]To support CAPA leader by means of their knowledge skill and experiences.
[][]To review and accept root cause and objective.
[][]To select best solution option(s) for evaluation.
[][]To select solution for implementation into routine use.
[][]Track and close out as per commitment and target date
[][]Provide physical evidence of CAPA closing

Manager, Quality Assurance

[][]Nominate CAPA Team.
[][]To select best solution option(s) for evaluation.
[][]To select solution for implementation into routine use.
[][]To approve implementation of the solution into routine use.
[][]To record and approve closure
[][]Define ongoing monitoring criteria of the Process Owner.
[][]To review and approve the root cause and objective.
[][]To assess the possible impacts on other functions
[][]Ensure that process is ‘in place’ and ‘in use’
[][]To approve implementation of the solution into routine use
[][]Approve changes to an agreed CAPA or date extension request

Procedure:

CAPA Objective

[][]After identification of a significant quality and compliance incident (triggered by any one of the interface process stated in scope) Departmental Head/CAPA Owner will prepare the [][]CAPA objective. Source of the CAPA objective may be anyone from the following:
[][]Formal investigation report according to SOP on Deviation & Investigation
[][]Audit findings and Audit report
[][]Significant risk in the Risk Register
[][]Investigation report triggered from OOS/Stability Failure/Market Complaints/Recall/ Change control
[][]Out comes from monthly quality review meetings

[][]CAPA objective constitutes the following information:
=>Current Situation/Problem to be solved
=>Actual or most probable root cause.
=>Criticality Classification (Critical/Major/Minor)
=>Time scale for resolving the issue depending on criticality.

[][]Departmental Head/CAPA owner is accountable for CAPA objective. Depending upon the criticality/priority settings in CAPA objective, CAPA owner will take the role of CAPA leader or assign a competent person as CAPA leader.
[][]The CAPA Leader will request for a reference number from the Quality Compliance. The number format will be as CAPA/YY/XXX, where YY represent for the last two digit of a year and XXX stands for the three digit sequential number derived from a CAPA register (Annexure-III) maintained by Quality Compliance personnel.

CAPA Team:

[][]Manager, Quality Assurance determines the Leader Depending upon the nature of CAPA objective and CAPA leader may form a team.
[][]For simple CAPAs one person may take the roles of Owner, CAPA leader and CAPA team.
[][]For complex CAPAs Operators, inspectors and others involved directly with the manufacture of affected product or processes should be considered for CAPA team membership.
[][]Based on the gravity, Functional Head/Department Manager will allocate resources to CAPA team.

Review & Source of CAPA :

[][]The CAPA team will review the source and all data gathered during preparation of investigation of incidence of CAPA to ensure that full understanding of the root cause.
[][]If team requires additional data they will identify and drive to collate it.
[][]Based on the risk analysis of the root cause, CAPA leader will define the criticality of the CAPA as critical, major or minor.

Determine the scope:

[][]The CAPA team will determine the possible impact of root cause on other functions/departments and record it as scope of CAPA.
[][]CAPA leader will record all the above information in the designated place of CAPA form (Annexure I)

Define and agree solution options:

[][]Determine Ideal Solution specifications
=>The CAPA team will prepare a list of criteria for an effective CAPA which will lead a robust and permanent solution to the problem. These will include any critical success factors, without which the solution will not work.
=>It may include resources required, particular people need to involve or get support from, or time constraints, cost and communication.

Develop a list of solutions

[][]The CAPA team will list all possible solution options either to eliminate the root cause permanently or to mitigate the problem where it is not possible to eliminate the root cause.

Assess the solutions

[][]The CAPA team will assess each solution option, or combination of options against ideal solution specification to determine the best solution option. At this stage the CAPA team considers practicalities such as cost effectiveness, ease of implementation, reduction of associated risk and ability to meet business needs.

Select the solution option (s)/Actions

[][]After assessment CAPA team will select the best solution option for implementation. For maximum CAPA only one selected option will meet all the criteria/requirement to eliminate/ mitigate the root cause. (At least mitigate the risk if it is not possible to eliminate the root causes).
[][]Where more than one solution options are available, select the solution which best meets the acceptance criteria.
[][]CAPA leader can escalate the issue to Monthly quality review meeting where it is not possible to define and select any solution for a CAPA objective.

Approval of proposed CAPA:

[][]Proposed CAPAs that require any trial or changes to process, ways of working, procedures or equipment, CAPA leader will raise Change Control which will be progressed through Change Control Procedure through SOP.
[][]For all major/critical CAPA, CAPA leader will consider the requirement of following at this stage:
[][]Requirements of revision/creation of any controlled documents (SOP, BMR or BPR) and associated training.
[][]Resume of operation until the CAPA is complete.
[][]CAPA leader will ensure the closing of Change Control within the defined timeframe.
[][]Then CAPA leader will submit the dully filled CAPA form (Annexure I) to Manager, Quality Assurance and Audit along with associated Change Control and validation report (if available).
[][]Manager, Quality Assurance will review and ensure that all necessary input and decision point is available in CAPA form.
[][]He/She will ensure that while developing the CAPA scope is clearly and comprehensively defined. If he/she finds any short coming CAPA will sent back for further review.
[][]After approval/authorization, QA personnel will post the CAPA in the CAPA tracking system and handover the original CAPA form to CAPA leader.

Closing of CAPA:

[][]CAPA leader will coordinate the implementation of CAPA within agreed timeframe and collect the short term monitoring data (if available).
[][]During implementation for any deviations, changes or delays to the plan, CAPA owner will raise a date extension request (Annexure II).
[][]QA Executive will ensure that an assessment of the delay has been properly conducted and will forward it to Manager, Quality Assurance.
[][]Manager, Quality Assurance will review the date extension request and the risk assessment conducted. If the justification and risk assessment appropriate, he/she will approve it and QA Executive will update the CAPA Tracking system accordingly.
[][]All date extension approvals will be formally endorsed in Monthly Quality Review Meeting.

[][]CAPA leader and CAPA owner both define the monitoring system for short and longer term monitoring of the effectiveness of the solution. Monitoring system may include any of the following (but not limited to):
=>Monthly Quality review meeting
=>Specification
[][]Duration and levels of monitoring (e.g. higher frequency initial, lower frequency longer term, extensive sampling for impacted batches etc.)
Note: For CAPA where Change Control is not required, CAPA leader and CAPA Owner directly define the monitoring criteria.

[][]After closing CAPA leader will submit the duly filled CAPA form along with closing evidences to Manager, Quality Assurance for verifying the effective closing of the CAPA. Manager, Quality Assurance will ensure that CAPA has been effectively closed.
[][]QA personnel will update the status of CAPA tracking system and post the necessary closing evidences.
[][]CAPA owner is responsible for implementing/sustaining the CAPA as routine activities.

Review of CAPA effectiveness:

[][]If requirement of long /short term monitoring data is defined as a part of monitoring system, CAPA owner will collate and communicate the monitoring data or trend to AGM, Quality Assurance for review.
[][]Executive, Quality Assurance will categorize, trend and sort the area/systems from where maximum CAPA has been triggered. He will conduct an unnoticed inspection at any time to verify the sustainable improvement of those particular systems.

Annexure:

Annexure I- Corrective and preventive action (CAPA) form
Annexure II- Date extension request
Annexure III- CAPA Issuance Log Book

CAPA Procedure Read More »

Sampling Procedure of Intermediate & Semi Finished (Bulk) Products

Sampling Procedure ,Purpose :

Sampling Procedure , To define the procedures for sampling of all intermediates and finished products.

Sampling Procedure , Scope :

This procedure is applicable for sampling of all intermediates and semi-finished products that are manufactured at XX Pharmaceuticals Limited (Both General and Sterile Block).

Definitions / Abbreviation:

[][]Intermediate Product: Partly processed material which must undergo further manufacturing steps before it becomes a bulk product.
[][]Finished Product: A medicinal product which has undergone all stages of production, including packaging in its final container.
[][]QCOM: Quality Compliance
[][]BMR: Batch Manufacturing Record
[][]BPR: Batch Packaging Record
[][]QC: Quality Control
[][]IPC: In-Process Check

Responsibilities:

[][]The roles and responsibility is as follows:

Executive/ IPC Inspector, Quality Assurance

[][]Responsible for sampling of intermediate, semi-finished (bulk) products as per the procedure

Asst. Manager, Quality Assurance

[][]Responsible for overall execution, supervision, control and implementation of sampling.

Manager, Quality Assurance

[][]Approval of the SOP.

Procedure:

Quantity of Intermediate (semi finished), control sample and stability sample (if any) shall be drawn as stated in the Annexure-I & II

Semi-finished (Bulk) Products Sampling:

[][]QA Executive shall collect the in-process samples.
[][]QA Executive shall ensure the completion of stage prior to sampling.
[][]Check the physical condition and labels on each container for specified details on the drum or container to be sampled.
[][]In case of powders / granules use dry SS sampling rod. Introduce the samplers vertically throughout the length of product and draw the sample from different depths of the product. Mix the sample and take a composite sample in the bag / beaker from each of the container sampled.
[][]QA Executive shall ensure that the specified quantity of sample as per Annexure–I & II is taken.
[][]In case of lubricated granules and blended powders/granules, draw at least three samples from three different locations and at different depths.
[][]LOD on granules should be carried out on mixed samples made from the samples of three locations.
[][]Samples of core tablets or capsules should be drawn at three times (start, middle and end time) of compression or encapsulation and a composite sample should be given to QC for complete analysis.
[][]QA Executive shall be assisted by Production Executive to ensure that the sampled containers are securely sealed after drawing the sample and ensure that the product is not exposed to atmosphere or moisture.
[][]QA Executive shall affix “Quarantine” label to containers and enter the sampling details in the respective Batch Production Record (BMR & BPR) and Sampling Advice Form (SAF) and shall forward the sample to QC for analysis along with SAF.
[][]Final blending sample shall be forwarded to QC for analysis when product strength is below or equal to 2.5 mg.
[][]In different stages parameters to be tested by QC as per finished product specification.

Control Sample / Stability Sampling:

[][]QA Executive shall select the random packed shippers and check the quantity per shipper, pack, label details and draw the sample from the shipper.
[][]QA Executive shall immediately replace the number of units taken as sample with the same number of units from the last shipper.
[][]QA Executive shall be assisted by production Executive to ensure sampled shipper is filled with appropriate quantity and closed properly.
[][]QA Executive shall affix “Quarantine” label on each pallet and enter the sampling details of Control samples and Stability samples in the respective batch records.
[][]The packs sampled, as Control sample shall be individually stamped as ‘Control Sample’ with red ink.
[][]Stability samples shall be charged into stability chamber as per stability plan.

Annexure:

Annexure-I: Intermediate And Semi finished (Bulk) Product Sampling Details (For QC)
Annexure-II: In process Sampling Details (For QA)

Sampling Procedure of Intermediate & Semi Finished (Bulk) Products Read More »

Process Validation

Process Validation, Purpose :

Process Validation, To describe the procedure for any process of manufacturing to be validated before putting into regular practice. The validation is to be performed following validation Master Plan, cGMP, and regulatory requirement. Also when technology transfer is executed the validation shall be as per customer requirement.

Process Validation, Scope :

All products to be manufactured in XX Pharmaceuticals Limited (Both General and Sterile Block) shall be validated as per authorized protocol.

Definitions / Abbreviation:

[][]PD: Product Development
[][]Process Validation: Process validation is a procedure used to ensure that a certain process produces consistent, desirable results over a period of time. It guarantees that a given method for making products allows them to meet predetermined standards in a cost-effective way.
[][]Process Validation Protocol: Process Validation Protocol is defined as a documented plan for testing a pharmaceutical product and process to confirm that the production process used to manufacture the product performs as intended. This includes a review of process variables and operational limitations as well as providing the sampling plan under actual use conditions.

Executive, Validation

[][]Responsible for preparation of protocol and summary report and co-ordinate the entire activity related to protocol.

Executive, Production/ PD

[][]To monitor the process, planning for validation activities.

Executive, QC

[][]To provide analytical support for various samples drawn during validation studies.

Engineering

[][]To provide the utilities, status of calibration & preventive maintenance

Manager, Quality Assurance

[][]Approval of Protocol and Report.

Procedure:

[][]For introduction of new product or process, process validation will be started after successful optimization of product/ process in production equipments/ environment (After the manufacturing of trial and pilot batches by Product Development)
[][]The first one/two batches shall be treated as optimization batch. Optimization batch (OB) will be manufactured as per recommendation of successful trial and pilot batches maintaining all GMP requirements for commercialization of the batch.
[][]Batch size of optimization batch (OB) should be equivalent to commercial batches and optimization of machine capacity should be considered properly.
[][]Total manufacturing procedure of optimization batch (OB) will be carried out as per the Optimization Batch Manufacturing Record (OBMR).
[][]During manufacturing of the optimization batch extensive sampling will be done as per the sampling plan of the product as per (annexure-III) and all parameters will be same as commercial Batch.

[][]The reference no. of the sampling plan of pre-process validation (Optimization) batch shall be given as follows.
SP/P-XXXXX/01
Where
=>SP stands for Sampling Plan
=>/ stands for separator
=>P-XXXXX stands for product code
=>01 stands for the version number of sampling plan.
[][]After standardization of all the process parameters from the optimization batch under the direct supervision of concerned PD, Production & QCOM Executive the process validation activities will be executed as per the Batch Manufacturing Record (BMR) as well as process validation protocol.
[][]If more than three optimization batches are required for setting all process parameters then it should be justified through risk assessment
[][]The selection of number of batches for process validation shall be defined in individual protocol. All protocols shall be as per the Format given in Annexure – I.
A validation team shall be consisting of multi-disciplinary team of personnel primarily responsible for conducting and or supervising validation studies.
[][]A team shall comprise Production, Quality Assurance, Product Development, Validation, Quality Control and Engineering personnel.
[][]The validation activity shall be carried out according to authorized product specific Protocol.
[][]The validation protocol shall contains Table of content (Index), approval, objective, scope, product details, validation team, responsibility, validation methodology, batches under validation, list of critical equipments & utilities, list of raw materials, Manufacturing Process Flow Diagram, Process Stages, Control Variables & Justification, list of critical process parameters, control variables & measuring response /justification, manufacturing and packing process, sampling plan, test parameters, acceptance criteria, environmental control, list of packaging materials, batch yield, deviation summary, process summary and conclusion.

[][]The validation and / or qualification status of all-relevant equipments & system checks as status of calibration of different gauges, thermometers, sensors, balances, etc. shall be verified during execution of validation activities. The analytical method will be validated before execution of the process validation activities.
[][]Process Validation Protocol number shall be given as follows.

=>PVP/P-XXXXX/001.
Where ,
=>PVP stands for process validation protocol
=>/ stands for separator
=>P-XXXXX stands for product code
=>001 stands for sequential number.

[][]Process Validation Report number shall be given as follows.
=>PVR/ P-XXXXX /001
Where
=>PVR stands for process validation report
=>/ stands for separator
=>P- XXXXX stands for product code
=>and 001 for sequential number.

[][]Training should be given to supporting staff who shall perform the validation and shall get engaged in manufacturing activities.
[][]Following considerations shall be exercised while conducting the process validation.
[][]Use same source of components for validation batches.
[][]The use of same equipment and facilities dedicated for commercial production & their operating ranges of critical processes.
[][]During processing of the validation batches, extensive sampling and testing shall be performed which will be stated on the specific protocol.
[][]However if blending uniformity is achieved at first time point, the blending of multiple time point may not be required to avoid de-mixing.

[][]Three consecutive batches shall be considered for the studies. Any intermittent deviation shall be investigated and study should be further continued with evaluation.
Complete testing shall be done on the final product of all batches under study.
[][]The validation batches may be individually released prior to concluding the whole validation study based on a risk assessment. Risk assessment reports should be issued for each batch manufactured.
[][]A detailed summary of all results, as required by the validation protocol, obtained from in- process controls, final testing and additional testing including the reference to the raw data documentation. The results have to be compared with their acceptance criteria as defined or referenced in the validation protocol.

[][]Results of any supplementary studies as defined in the validation protocol.
[][]Any corrective or follow-up actions needed.
[][]Actions to be taken in the event of the acceptance limit being exceeded.
[][]After compilation of batches review the results, parameters and standardize the critical parameters.
[][]Validation protocols shall be used for the purpose and a conclusion for the process under consideration shall be drawn in validation report for all the three batches.
[][]The report shall specify the acceptance criteria and shall contain conclusions derived from the scientific study. All reports shall be as per the Format given in Annexure – II.
[][]Upon consideration of the review, recommendations shall be made on the extent of monitoring and the in-process controls necessary for routine production.

[][]The approved recommendation on the extent of monitoring and the in-process controls shall be incorporated into the Batch Manufacturing Record & Batch Packing Record or into appropriate standard operating procedures.
[][]Required number of samples shall be collected as per product specific stability protocol for stability study during the process validation study.
Revalidation: Revalidation shall be considered under following conditions.

[][]Whenever there is change in vendor for active ingredient and/or such excipients, which are more than 50 % by weight of the batch size.
Change in equipment (which can have impact on product quality).
[][]Change in batch size.
[][]Major change in the process.
[][]In case of revalidation the protocol and report number will be same as previous and the version number will be changed accordingly. The details about the next version will be included in the version details.

Validation Review:

[][]The frequency of validation review report will be three years and the report will include the parameters like introduction, scope, batch manufacturing data, equipment maintenance history, change control history, deviation history, failure investigation, audit recommendation, market complaints, summery report and conclusion.

Annexure:

Annexure-I: Process Validation Protocol
Annexure-II: Process Validation Report
Annexure-III: Sampling plan of Pre-Process Validation (Optimization) Batch

Process Validation Read More »

Instrument Numbering System at Laboratory

Instrument Numbering, Purpose:

Instrument Numbering, To provide a system for allocating identification number to Laboratory instrument in order to have better traceability and reference in all related documents.

Instrument Numbering, Scope:

This SOP is applicable to all Laboratory instruments and equipment’s installed in quality control laboratory, microbiology laboratory, product development laboratory and IPC laboratory of General block and Sterile block at XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.

Responsibilities:

[][]The roles and responsibility is as follows:

Concerned Personnel

[][]He / she shall be responsible for assigning / allocating the sequential number to all equipment / instrument.

Quality Assurance Personnel

[][]He / she shall be responsible for effective implementation and monitoring of procedure.

Manager, Quality Assurance

[][]To ensure effective implementation of SOP.
[][]To approve the document.

Procedure:

[][]Numbering for Individual Laboratory Instrument:
[][]Each individual Laboratory instrument shall be assigned on unique identification number.
[][]Concerned department shall assign the sequential number to all instruments at the time of Installation Qualification and record the details in respective department register as per Annexure-II.
[][]Do not repeat the same number to another instrument.
[][]Give identification no. to all instruments as XXX/YY/000.

Where,
=>XXX corresponds to three alphabets denoting the area code of the Laboratory.
=>YY corresponds to two alphabets denoting the instrument name as per approved list available in Annexure-I.
=>000 corresponds to three numerical figures starting from 001 denoting the number of instrument in continuous manner.
=>As per Example of Balance GQC/BA/030

Where,
=>GQC = Corresponds to three alphabets denoting the Area code of Quality Control Laboratory at General Block.
=>BA = Corresponds to two alphabets denoting the instruments code.
=>030 = Number of instruments in continuous manner.

The Area Code for each Laboratory is given below:

Area Description/ Area Code

[][]Quality Control Laboratory (General Block)/ GQC
[][]Quality Control Laboratory (Sterile Block)/ CQC
[][]In-Process Laboratory (General Block)/ GIP
[][]In-Process Laboratory (Sterile Block)/ CIP
[][]Product development Laboratory (General Block)/ GPD
[][]Product development Laboratory (Sterile Block)/ CPD
[][]Microbiology (General Block)/ GMB
[][]Microbiology (Sterile Block)/ CMB

[][]Quality Assurance will prepare the Master list of Laboratory instrument with identification number and get it approved by Manager, Quality Assurance as per Annexure-III.
[][]Update the list and approve it whenever require and give serial number to list prepared.
[][]All instruments will be tagged containing instrument name and Identification number (Bold Type). Format of instruments identification tag is as follows:

INSTRUMENT / DEVICE

Name:

ID Number:

[][]In case of advent of new type of instruments, there is an option for extending Annexure-I by hand writing of Manager, Quality assurance with signature and date without reviewing the whole SOP.
[][]For this, the respective department will inform to it to the Quality Assurance Department for new code number.
[][]The new instrument (Handwritten by Manager, Quality Assurance) will be included in SOP during the next version.

Annexure:

Annexure-I: Code number for Laboratory Instrument.
Annexure-II: Laboratory Instrument Register.
Annexure-III: Master List of Laboratory Instrument

Instrument Numbering System at Laboratory Read More »

Batch Tailing of Products

Batch Tailing, Purpose:

Batch Tailing, To establish general guidelines for batch tailing of products. It is the process whereby residual defective product (e.g. Granules, broken tablets, capsules etc.) which is satisfactory on quality, is to be added to the subsequent batches as a relatively small portion of the final batch quantity (where to be added) without affecting the quality of finished product.

Batch Tailing, Scope:

This procedure is applicable for oral solid dosages form that manufactured at XX Pharmaceuticals Limited (both General and Sterile Block).

Definition / Abbreviation:

[][]N/A

Responsibilities:

[][]The roles and responsibility are as follows:

Production Personnel

[][]To ensure that the residual product to be added is physically and chemically okay and the entire process is done following SOP.

Concerned department head

[][]To ensure that above procedure is followed properly.

Quality Assurance personnel

[][]To monitor the entire process done according to SOP.

Manager, Quality Assurance

[][]Approval of the SOP.

Procedure:

Storage and Selection Criteria of Batch Tail:

[][]The product/material to be added shall be kept in a double lined poly bag in a container with lid closed by mask tape.
[][]The container and the polybag shall be labeled properly mentioning Product Name, Batch No., quantity and date of manufacturing and to be stored in cool & dry place of well-defined areas of production.
[][]Only Product from approved batches can be added.
[][]If any batch is reprocessed once, leftover material of that batch must be disposed immediately.
[][]Addition of any leftover material/product shall be completed within the same manufacturing month or subsequent month. In case of slow moving product, it shall be completed with next manufacturing batch but the difference between two batches shall not exceed more than 3 months.
[][]Products/materials must not be added from a batch which is kept for more than three months (i.e. 90 days) in bulk condition (e.g. bulk tablets, bulk powder of capsules, blended pellets etc.).
[][]Within above time limits, if there is any sign of deterioration of the product is seen visually, they must be discarded.
[][]The weight of the material/product to be added should be equal to or less than 5% of the original batch size (weight) of the product. Maximum 10% can be allowed with justification.
[][]If the quantity is huge, a reprocessed batch can be manufactured using all tailed quantity. In that case, Batch No., Mfg. & Exp. Date shall be according to the oldest batch of accumulated batches.
[][]Powder for Suspension cannot be added to any other batch(s). This is to be discarded with proper reconciliation in the batch document.

Steps for prior Approval of Batch Tailing

[][]Concerned department Executive shall raise Batch Tailing Form (Annexure-I) and fill up the relevant information in section A & B. There must be clear statement regarding the reason for Batch tailing.
[][]In section C of Batch Tailing Form, Manager of concerned department shall provide his comments ensuring the statement provided by his officer and suitability of reprocessing/reworking of the product.
[][]Before taking decision of addition of batch tailings to subsequent batch, physical verification of batch tails must be carried out by Quality Assurance Executive and shall record observation in section D of Batch Tailing Form.
[][]In section E of Form, Manager, Quality Assurance shall give comments to ensure its suitability of re-use.
[][]In section F of Batch Tailing Form, comments shall be given by General Manager, Plant.
[][]In section G of Form, Head of Quality Assurance shall provide comments regarding approval.
[][]The approved Batch Tailing Form shall be the part of batch records

Annexure:

Annexure – I: Batch Tailing From

Batch Tailing of Products Read More »

Good Documentation Practice

Good Documentation Practice, Purpose:

Good Documentation Practice, To define the common practice to be followed for data entry in all GMP / GLP records.

Good Documentation Practice, Scope:

This procedure is applicable to all GMP / GLP records filled manually at XX Pharmaceutical Limited (Both General & Sterile Block). This SOP is general guideline and will be superseded whenever any specific requirements are mentioned in other SOP or approved document.

Definitions / Abbreviation:

[][]GMP / GLP Records: GMP / GLP records are defined as all records which directly or indirectly and individually or collectively control the strength, identity, safety, purity and quality of drug product.
[][]Annotate: To add explanatory notes.
[][]SOP: Standard Operating Procedure.
[][]N/A: Not Applicable

Responsibilities:

[][]The roles and responsibility is as follows:

Concerned Personnel

[][]To carry out the documentation as mentioned in SOP.

Department Head or Designee

[][]To ensure training and implementation of SOP.

Manager, Quality Assurance

[][]To ensure implementation of SOP.

Procedure: Good Documentation Practice

[][]General Guidelines for documentation practices:
[][]Sign and date all data entries on the date of data entry, as applicable.
[][]Date to be written numerically in the DD/MM/YY form. E.g. write 13/01/16 for 13th January 2016.
[][]Time to be written numerically in the HH:MM form in the document using 12 hours cycle daily. For e.g., 8:30 AM, 4:30 PM etc.
[][]Time duration to be written as shown below:
[][]e.g. If for some process the observed time duration is 2 minutes and 30 seconds then it’s should be written as 2min 30 sec and not as 2:30min.
[][]In case of wrong entry, strike out with single line and put initial and date nearby it. Do not overwrite or block the wrong entry.
[][]Do not leave blank space, Write N/A.
[][]Do not use the ” if the entry is repeated in next line.
[][]Use of pencil is not allowed.
[][]Correction fluid / white ink / eraser should not be used.
[][]Entries to be made in legible handwriting.
[][]Unusual observations shall be recorded, signed and dated.
[][]Entries in logbook shall be done in the chronological order.

General Guidelines for using indelible ink pen:

[][]Write all GMP records only with permanent BLUE indelible ink pen.
[][]Permanent BLUE indelible ink pen should be used for signing of master documents.
[][]The QA supervisor should use the permanent GREEN indelible ink pen to sign after checking the data on shop floor.
[][]Data entries should be recorded, signed and dated immediately after the completion of each activity, as applicable.

Correction of Recording Error / Overwriting or Incorrect Entry:

[][]In case of any wrong entry, do not over write or block the entry to make it obscure or unreadable. Strike out the wrong entry with straight single line passing through incorrect entry in [][]such a way that it remains readable.
[][]Make correct entry nearby it.
[][]For major changes annotate the actual reason for the correction or change, as the case may be.
[][]The correcting person shall put the initials along with date on which correction was done.
[][]Suppose ‘Cleaned’ is recorded in place of ‘Ensured’ by mistake on 10/01/XX and observed later during BMR review on 18/01/XX, it can be corrected at later date in the following way:
[][]Correct way for Correction on 18/01/XX:
[][]Initial Cleaned Ensured
[][]Date
[][]If space is not sufficient for correction, strike out the wrong entry with single line and highlight the same with an asterisk (*) nearby it. Define the asterisk at the bottom of the page and [][]Correct the wrong entry with initial and date.
[][]Entry of Missed Step:
[][]Entry of any missed step can be done later only if it can be proved that the step had been performed but the doer/performer and/or checker failed to document the same.
[][]The person making entry of missed step shall put the initials along with the date on which entry is done nearby entry of missed step.
[][]Working with Blank or Unused page/space :
[][]Do not leave blank space in any GMP record.
[][]Strike out any blank space or page with cross line and write in between the line N/A.
[][]Put initial and date at the end of the line, e.g., for following unused space strike out as specified :

Rounding – off of values:

[][]The rounding off values is applicable only to the calculations and not to the observed readings. Limits which are fixed numbers shall not be rounded off.
[][]e.g., If limit is 2 – 8 °C, then observed value 8.2 cannot be rounded off. Any value or figure which displayed by any equipment/instrument shall not be rounded off, e.g. if pH meter displayed is 3.79 than it should be mentioned as such and should not be rounded off to 3.8.
[][]When rounding off of any value is required, follow the below procedure.
[][]If last digit is equals to or greater than 5, it is eliminated and the preceding digit is increased by one.
[][]If last digit is smaller than 5, it is eliminated and the preceding digit remains unchanged.
[][]For examples see the below Illustration:
[][]Illustration of Rounding of Numerical Values for comparison with Requirements
[][]Requirements: Product Yield Limit (99.0% to 101.0%)

Unrounded Value to Rounded Value

[][] 98.926 shall be 98.93
[][] 100.124 shall be 100.12
[][] 99.655 shall be 99.66

Assigning Due Date:

[][]For assigning Due Date in all GMP records, calculate due date as per frequency for that particular activity from the day on which that activity is performed.
[][]Status of the activity can be valid up to the due date.
[][]For example, consider the case of assigning due date for re-cleaning of pre-filter for which cleaning frequency is 15 days.
[][]Suppose cleaning of pre-filter is done on 02/01/XX, since frequency of pre-filter is 15 days, due date for re-cleaning of pre-filter can be assigned 16/01/XX and cleaning can be considered valid up to 16/01/XX.
[][]Record all information in legible handwriting in all GMP records.
[][]Printouts from the instruments relevant to the analysis shall be retained and no such document shall be discarded even if they are not of use in the calculation.

Additional Documentation Practices for Quality Control Laboratory:

[][]Entries like “Complies/Does not comply” only allowed for the binary observations but the binary observation shall be specific.
[][]E.g. Limit test shall mention the observation noticed and TLC shall mention the comparison with the spot.
[][]Calculations shall be documented and rounding off shall be done as per SOP.
[][]Concordance of another analyst shall be taken for observations of subjective tests. E.g. limit tests, TLC plates etc. Both the analyst shall initialize and sign the observation.
[][]Printouts from the instruments relevant to the analysis shall be retained and no such document shall be discarded even if they are not of use in the calculation.

Annexure: Good Documentation Practice

N/A

Good Documentation Practice Read More »

Labelling Procedure

Labelling , Purpose :

Labelling , To describe the procedure for status labeling to identifying correct status of Equipment, area, Stage of product, Raw Material & Packaging Material at a given point of time.

Labelling , Scope :

This procedure is applicable for all materials/products received and stored in General Block & Sterile Block at XX Pharmaceuticals Ltd. that has the potential to affect GMP and quality, safety or efficacy of the finished product.
This procedure is also applicable for control of status identifying labels, process label and product labels used in Production, Warehouse, Quality Control and Quality Assurance departments in General Block & Sterile Block at XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]Labeling: Displaying status and identity of a material or a thing.

Responsibilities:

[][]The roles and responsibility is as follows:

Concerned Department

[][]Concerned department Officers/ Executive shall be responsible to carry out the activity as per procedure.
[][]To affix the status label as per procedure.

Head, Concerned Department

[][]Concerned Department Heads shall be responsible for effective implementation of procedure and activities.

Quality Assurance

[][]To ensure implementation of labeling procedure & proper labeling as per SOP.

Manager, Quality Assurance

[][]Approval of the SOP.
[][]To ensure the overall implementation of the SOP.

Procedure:

[][]In order to avoid mix-ups and contamination, for easy identification and traceability, of product and to ensure working as per GMP standards it is important to affix status label at each stage of process on equipment’s, products, containers, accessories and areas. Labels of various types are used in manufacturing functions.
[][]The purpose, type and use of each label are described as below.

General procedures for label handling:

[][]Every status-identifying label shall have distinctive format number and master copy for all computers generated and printed label formats shall be preserved securely under lock and key with Manager, Quality Assurance.
[][]Each and every container of active pharmaceutical ingredients (APIs), excipients, raw materials, intermediate products, primary and printed packaging components will have to be labeled denoting proper status.
[][]Every supplier batch will have status label (e.g. Passed label) with one unique batch/ lot number.
[][]For tertiary packing materials (product nonspecific i.e. shipper carton, master carton) pallet wise labeling process will be followed.
[][]All labels will be preprinted self-adhesive labels which provide blank space for printing/ writing necessary information.
[][]After printing/ generating of status label an authorized person will verify the correctness of printing.
[][]Containers/packs where self-adhesive label cannot be pasted securely (Sack/ polythene bag) transparent tapes will be used at every side for affixation. Stapler pin will never be used for affixation of label.
[][]No material/ product/equipment without status label shall be stored either in the warehouse or production floor.
[][]Warehouse personnel cannot issue material from any container to production where ‘PASSED’ label is not available.
[][]During dispensing of active raw materials, Officer/ Executive will ensure that every container contains three status label (QUARANTINED, SAMPLED, UNDER TEST and PASSED).
[][]In case of other raw materials (excipients) & packaging materials, all containers/ pack/ pallet must have ‘UNDER TEST’, ‘PASSED’ and ‘QUARANTINED’ label. ‘SAMPLED’ labels will be found between ‘QUARANTINED’ and ‘UNDER TEST’ label only on containers from which the samples were taken.

[][]Label must not be applied on the container lids.
[][]Labels will be applied on the body of the containers so that it will be easily visible. Label must not be overwritten and erased out.
[][]Labels will be handled securely in a segregated manner (under the custody of an authorized person) with controlled access.

Quarantined Label:

[][]After receipt and checking of incoming materials, warehouse Officer/ Executive will print ‘QUARANTINED’ labels with necessary information for all containers/packs for each batch of materials.
[][]Authorized warehouse personnel will provide all the entry required for ‘QUARANTINED’ label.
[][]Warehouse Officer/ Executive will verify and ensure that all the information printed on the labels of first sheet is correct and then will give command to authorized warehouse personnel for printing total ‘QUARANTINED’ labels required for the respective lot. Any label with printing error will be destroyed instantly.
[][]Warehouse Officer/ Executive will sign (issued by) and authorized person of the warehouse will affix all ‘QUARANTINED’ labels on each container of the incoming materials.
[][]This label is printed with black overprint on Orange background.

Approved Label:

[][]Quality Assurance Executive shall affix the ‘Approved Label’ on respective process container after receiving the certificate of analysis of that material / Product from QC.
[][]Quality Assurance Executive shall issue this label to approving In-process Granules/Powder, Uncoated /Coated Tablet for Work in progress.
[][]This label is printed with black overprint on Blue background.

Sampled Label:

[][]On receipt of Good Received Note (GRN) from warehouse, QC personnel will follow the SOP for Raw material sampling and release procedure or SOP for Packing material sampling and release procedure to determine the sampling plan and the number of the containers to be sampled.
[][]QC Officer/ Executive/ authorized person will issue and print required ‘SAMPLED’ labels according to sampling plan.
[][]After sampling, duly signed ‘SAMPLED’ label will be affixed on the containers or packs from which samples are withdrawn.
[][]The ‘SAMPLED’ label will be affixed beneath the ‘QUARANTIED’ label in a cascading manner (slight overlapping) without hiding any information of ‘QUARANTIED’ label.
[][]This label is printed with black overprint on Yellow background.

Hold Label:

[][]Manager, Quality Assurance may hold any raw material, packaging material or finished product when necessary.
[][]Quality Assurance personnel will print ‘HOLD’ label with necessary information.
[][]After signed by authorized person, Quality Assurance personnel will affix ‘HOLD’ label on the pallet/ container that will be hold for long time for a decision of passing or rejection.
[][]When final decision of passing or rejection is taken, Quality Assurance personnel will remove the ‘HOLD’ label and destroy them. Then, ‘PASSED’/ ‘REJECTED’/ ‘APPROVED’ labels will be affixed.
[][]This label is printed with black overprint on orange background.

Passed Label:

[][]QC Officer/ Executive will follow the SOP for Raw material sampling and release procedure or SOP for packing material sampling and release procedure and issue the ‘PASSED’ label.
[][]QC officer / Executive will take required sheets of blank ‘PASSED’ labels. The quantity of ‘PASSED’ label will be based on number of containers/packs for each batch of materials
Officer/ Executive, QC will provide all the entry required for ‘PASSED’ labels and take the print-out of one page first.
[][] Another Officer/ Executive, QC will verify and ensure that all the information printed on the first sheet of labels is correct and then will give the command for printing total ‘PASSED’ labels required for the respective lot. Any label with printing error will be destroyed instantly. Officer/ Executive, QC will sign ‘PASSED’ labels.

[][]Authorized QC person will affix the ‘PASSED’ label on each and every single container of raw materials or packaging materials with the help of warehouse personnel.
[][]‘PASSED’ label will be affixed just beneath the ‘UNDER TEST’ label in a cascading manner (slight overlapping) without hiding any information of previous label.
[][]This label is printed with black overprint on Green background.

Rejected Label:

[][]QC Officer/ Executive will follow the SOP for Raw material sampling and release procedure or SOP for packing material sampling and release procedure and issue the ‘REJECTED’ label.
[][]QC officer will take required sheets of blank ‘REJECTED’ labels. The quantity of ‘REJECTED’ label will be based on number of containers/packs for each batch of materials
[][]Officer/ Executive, QC will provide all the entry required for ‘REJECTED’ labels and take the print-out of one page first. Another Officer/ Executive, QC will verify and ensure that all the information printed on the first sheet of labels is correct and then will give the command for printing total ‘REJECTED’ labels required for the respective lot. Any label with printing error will be destroyed instantly.
[][]Manager, QC will sign ‘REJECTED’ labels.
[][]Authorized QC person will affix the ‘REJECTED’ label on each and every single container of raw materials or packaging materials with the help of warehouse personnel.
[][]‘REJECTED’ label will be affixed just beneath the ‘QUARANTIED’ label or ‘UNDER TEST’ label in a cascading manner (slight overlapping) without hiding any information of previous label.
[][]This label is printed with black overprint on Red background.

Under Retest Label:

[][]Ware house Officer will identify any requirement for retesting of materials and immediately paste a ‘UNDER RETEST’ label on the container just beneath the previous ‘PASSED’ label and transfer the material to quarantined area. Warehouse Officer will inform the Manager, QC to arrange sampling for retesting
[][]This label is printed with black overprint on Yellow background.

Returned label

[][]The ‘RETURNED’ Label is displayed on the container/material for identification of Product status.
[][]Concerned Department shall affix this label on excess material that is to be left after Primary Processing, e.g Drying/ Pulverization/ packaging operation.
[][]Ensure that the materials returned are clean, free of dust, properly covered and in uniform countable bundles or pack.
[][]This label is printed with black overprint on White background.

Cleaned Card Label

[][]The “CLEANED” label is displayed for the identification status of the equipment after completion of cleaning activity.
[][]Use this label after complete cleaning, as per SOP.
[][]In case of start of the operation, filled this label to be affixed in BMR/BPR.
[][]This label is printed with black overprint on green background.
[][]Following are the details to be filled up in the respective blank spaces. Label to be filled by operator / supervisor.
[][]Equipment Name: Name and/or ID no of the equipment, which is cleaned.
[][]Previous Product: Name of the product for which cleaning activity is completed in that particular equipment.
[][]Batch No.: Batch No. of the above product.
[][]Date of cleaning: Date on which equipment is cleaned.
[][]Use on or before: Date before which equipment can be used.
[][]Cleaned by: Signature or name of the person by whom equipment is cleaned.
[][]Checked by: Signature of production supervisor after verification of the filled contents in the label and after visual verification of cleanliness of the equipment.
[][]Verified by: Signature of the QCOM person, after visual verification of cleanliness of the equipment’s.
[][]To be used for product: The product which will be taken for process after the equipment cleaning.
[][]Batch No.: Batch no. of the product which will be taken for process after equipment cleaning.

Partially Cleaned Label

[][]The PARTIALLY CLEANED label is displayed for the identification status of the equipment after completion of cleaning activity.
[][]Use this label after partial cleaning, as per SOP.
[][]In case of start of the operation, filled this label to be affixed in BMR/BPR.
[][]This label is printed with black overprint on Yellow background.
[][]Followings are the details to be filled up in the respective blank spaces. label to be filled up by the operator/ supervisor.
[][]Equipment Name: Name and/or code no of the equipment, which is cleaned.
[][]Previous Product: Name of the product for which cleaning activity is completed in that particular equipment.
[][]Batch No.: Batch No. of the above product.
[][]Date of cleaning: Date on which equipment is cleaned.
[][]Use on or before: Date before which equipment can be used.
[][]Cleaned by: Signature or name of the person by whom equipment is cleaned.
[][]Checked by: Signature of production supervisor after verification of the filled contents in the label and after visual verification of cleanliness of the equipment.
[][]Verified by: Signature of the QCOM person, after visual verification of cleanliness of the equipment’s.
[][]To be used for product: The product which will be taken for process after the equipment cleaning.
[][]Batch No.: Batch no. of the product which will be taken for process after equipment cleaning.

To be Clean Label:

[][]This label is displayed for the identification status of the equipment, accessories and containers after its use.
[][]Followings are the details to be filled up in the respective blank spaces. label to be filled up by the operator/ supervisor.
[][]Previous Product: Name of the product for which processing activity is completed in that particular equipment.
[][]Batch No.: Batch No. of the above product.
[][]Signature: Signature of the production supervisor after verification of the filled contents in the label.
[][]Date: Date on which the equipment is due for cleaning.
[][]This label is printed with black overprint on Orange background.

Loose Label:

[][]‘Loose’ Label is to be affixed on loose container/shipper by Production Department.
[][]This label is printed with black overprint on White background.
[][]Executive, Production will provide all the entry required for ‘Loose’ labels and take the print-out. Any label with printing error will be destroyed instantly.

Material Dispensing Slip Label:

[][]This label is displayed for the identification status of the Dispensed Material.
[][]Use this label during of dispensing of material as per SOP.
[][]Officer/ Executive, Production will provide all the entry required for this label and take the print-out.
[][]In case of start of the operation, Executive, Production will affix this label in BMR.
[][]This label is printed with black overprint on White background.
[][]Followings are the details to be filled up in the respective blank spaces.
[][]Balance No.: Name of the Balance ID
[][]Operation: Material dispense for either Granulation or Coating.
[][]Material: Name of the Raw material
[][]Code: Code No. of the Raw material
[][]Lab Ref. No.: Lab Control No. of the Raw material
[][]Product: Name of the product that is to be manufactured.
[][]Batch No. : Batch no. of the concerned product.
[][]Batch size: Actual batch size of the concerned product.
[][]Gross Wt.: Total weight (wt) of the filled container without lid in kilogram (kg).
[][]Tare wt.: Weight of the empty container along with Polyethylene bags without lid before taking it in use in kg.
[][]Net Wt.: Subtract the tare wt. from gross wt. in kg.
[][]Container No.: Number of that particular container out of total no. of container used for the above batch.
[][]Dispensed by: Signature of dispensing Operator
[][]Checked by: Signature of Production Executive after verification of the filled contents in the label.
[][]Verified by: Signature of QCOM officer after verification of the filled contents in the label.

Process Label:

[][]This label is displayed on the container for identification of the product status.
[][]This label is to be used on the container during the manufacturing stage. For Example: Under sifting, under granulation, under solution preparation, Ready for Granulation / Drying / [][]Blending / Solution ready for coating.
[][]This label is printed with black overprint on White background.
[][]Following are the details of preprinted label to be filled up in the respective blank spaces and to be filled by operator / supervisor.
[][]Product: Name of the product collected / to be collected in the container.

[][]Batch No.: Batch no. of the concerned product.
[][]Status: Stage in which the product is ready for next step.
[][]Container No.: Number of that particular container out of total no. of container used for the above batch.
[][]Batch Size: Actual batch size of the concerned product.
[][]Mfg. Date & Exp. Date: Manufacturing and Expiry date of the concerned product.
[][]Gross wt.: Total weight (wt) of the filled container without lid in kilogram (kg).
[][]Tare wt.: Weight of the empty container along with Polyethylene bags without lid before taking it in use in kg.
[][]Net wt.: Subtract the tare wt. from gross wt. in kg.
[][]Checked by: Signature of Production officer after verification of the filled contents in the label.

Product Label:

[][]This label is displayed on the Shipper for identification of the product status.
[][]This label is to be used on the Shipper during the Secondary Packaging Operation.
[][]This label is printed with black overprint on White background.
[][]Following are the details of preprinted label to be filled up in the respective blank spaces and to be filled by operator / supervisor.
[][]Product: Name of the product collected / to be collected in the shipper.
[][]Batch No.: Batch no. of the concerned product.
[][]Mfg. Date & Exp. Date: Manufacturing and Expiry date of the concerned product.
[][]Pack Quantity: Total no. of pack in Shipper.
[][]Sr. No.: Total No. of Shipper

[][]Packed by: Name / sign of the Operator /Supervisor who are involved in shipper Making & closing.
[][]Storage Condition: Storage Condition of the concerned product.

Area / Equipment Label:

[][]This label is used to exhibit the process that is being carried out in the area/equipment, tick (√) whichever is applicable.
[][]This label is printed with black overprint on Green background.
[][]The area is labeled at the start-up of the batch.
[][]Following are the details to be filled up in the respective blank spaces. Label to be filled by operator / supervisor.
[][]Product: Name of the product taken or to be taken for processing on that particular equipment.
[][]Batch No.: Batch number of the above product.
[][]Batch size: Actual batch size in written in the BMR.
[][]Status: Particular stage of activity in process.
[][]Checked by: Signature of Production supervisor after verification of the filled contents in the label.
[][]Date: Date on which the process takes place.

Retention Sample:

[][]QC / QA officer shall affixed sample Label on the sample Poly bag or container which is to be sample for retaining.
[][]This label is printed with black overprint on White background.

[][]Officer/ Executive, QC or QCOM will provide all the entry required for ‘Retention Sample’ labels.

Cleaned Label:

[][]This label is displayed for the identification status of the accessories and containers after completion of cleaning activity.
[][]This label should not be attached with BMR/BPR.
[][]This label on containers and accessories should be defaced with a cross-line and destroyed when taken for use.
[][]In case of start of the operation, this label has to be removed from container and ‘ Process’ label to be affixed.
[][]In case of start of the operation, this label has to be removed from accessories and ‘Area/ Equipment’ label to be affixed.
[][]This label is printed with black overprint on Green background.

Under Test Label:

[][]This label is displayed on the container/ Packet for the identification status of the material/product after sampling for QC Test.
[][]QC / QCOM Executive shall affix this Label after completion of sampling activity.
[][]This label is printed with black overprint on Yellow background.

Annexure: Download all here

Annexure-I: Blank format for ‘Quarantined’ label.
Annexure-II: Blank format for ‘Approved’ label.
Annexure-III: Blank format for ‘Sampled’ label.
Annexure-IV: Blank format for ‘Hold’ label.
Annexure-V: Blank format for ‘Passed’ label.
Annexure-VI: Blank format for ‘Rejected’ label.
Annexure-VII: Blank format for ‘Under Retest’ label.
Annexure-VIII: Blank format for ‘Returned’ label.
Annexure-IX: Blank format for ‘Cleaned’ label.
Annexure-X: Blank format for ‘Partially Cleaned’ label.
Annexure-XI: Blank format for ‘To Be Cleaned’ label.
Annexure-XII: Blank format for ‘Loose’ label.
Annexure-XIII: Blank format for ‘Material Dispensing Slip’ label.
Annexure-XIV: Blank format for ‘Process’ label.
Annexure-XV: Blank format for ‘Product’ label.
Annexure-XVI: Blank format for ‘Area/ Equipment’ label.
Annexure-XVII: Blank format for ‘Sample’ label.
Annexure-XVIII: Blank format for ‘Retention Sample’ label.
Annexure-XIX: Blank format for ‘Cleaned’ label.
Annexure-XX: Blank format for ‘Under Test’ label.

Labelling Procedure Read More »

Batch Numbering and Coding System

Batch Numbering, Purpose :

Batch Numbering, The purpose of this SOP is to describe the procedure of batch numbering system of finished product and issuing code number of raw, packaging and finished product.

Batch Numbering, Scope :

This procedure is applicable for coding of all raw materials, packaging materials, finished products and batch numbering system of finished product at XX Pharmaceuticals Limited (Both General and Sterile Block).

Definitions / Abbreviation:

[][]Batch Number: A distinctive combination of numbers and/or letters which uniquely identifies a batch on the labels, its batch records and corresponding certificates of analysis, etc.
[][]Code Number: An arrangement of numbers providing a unique identity to the items which they are assigned.

Responsibilities:

[][]The roles and responsibility is as follows:

Executive/ Manager, Product Development

[][]To inform and request Supply Chain department that the new materials to be used for product development.

Executive/ Manager, Supply Chain

[][]Issue the unique material code number of each raw material and packaging materials and as well as finished product

Executive/ Manager, PMD

[][]To inform and request Supply Chain Department to issue material & product code for new products.

Executive/ Manager, Quality Control

[][]Implementation of the total coding system.

Executive/ Manager, Quality Assurance

[][]Implementation of the total coding and batch numbering system.

Executive/ Manager, Production

[][]Implementation of the total coding and batch numbering system

Manager, Quality Assurance

[][]Approval of the SOP.
[][]To ensure that the implementation of the system as per SOP.

Procedure:

Raw Material Coding System:
[][]Maintain seven alphanumerical characters (first three characters are alphabetic and last four characters are numerical) for Raw Material Coding System.
[][]Start the coding with ‘RM’ which stands for ‘Raw Material’ and it is common for every raw material coding system
[][]For the Active Raw Material select ‘A’ as the third character of the code. When the raw material is excipient then select ‘E’ instead of ‘A’.
[][]At last specify the code number with four numerical characters to indicate the separate material. Following this procedure, raw material code for the first enlisted Active Material (API) will be RMA0001 and the second one (API) will be RMA0002.
[][]When the same material has different categories (such as compacted, granular, pharma grade etc.) then for every category, a new code number will be generated maintaining previous procedures.
[][]For example: Raw Material Code Number ‘RMA0001’ stands for
RM=Raw Material
A=Active (In case of Excipient it will be ‘E’)
0001=Individual number of raw material

Packaging Material Coding System:

[][]Maintain seven alphanumerical characters (first four characters are Alphabetic and last three characters are numerical) for Packaging Material Coding System.
[][]First characters which stands for packaging material. Second character will be changed for primary and secondary packaging material, When primary packaging material it will be ‘P’ and when secondary packaging material it will be ‘S’.
For example
=>PP= Primary Packaging Material
=>PS= Secondary Packaging Material

[][]Next two characters which stand for sub category of packaging material. It will be changed for every sub category of packaging material as Annexure-I.
[][]Last three characters which stand for sequential number. Every sub category material starts with sequential number 001. Such as
=>AB-001= Alu- Bottom foil
=>TF-001= Alu-Lid foil
=>And so on

[][]The sequential number will be changed when different types of materials come in same sub category. For example
=>AB-001= Alu –Bottom foil 206 mm
=>AB-002= Alu –Bottom foil 183 mm
=>And so on

[][]Finally the coding system of packaging material is like
=>PP-AB-001
Where
=>PP stands for primary packaging material
=>AB-001 stands for alu bottom foil 206 mm

Finished Product Coding System:

[][]Maintain seven alphanumerical characters (first digit is alphabetic and last five digits are numerical) for finished product coding system.
[][]Start the coding with ‘P’ which stands for finished product. P is common for every finished product code numbering system.

[][]The last five digits 00001 is sequential number. It will be changed in every finished product coding system. It will be also changed when same product in different strength. For example finished product code of Cexoral 200 capsule is P-00001 and Cexoral 400 capsule is P-00002.
[][]Finally the finished product coding system is P-00001
[][]Where P stands for finished product
[][]is dash
[][]00001 stands for sequential number of individual product with strength.

Batch Numbering System for Finished Product:

[][]Maintain six characters (All six digits are numerical) for batch numbering system.
[][]First two digits stand for year. It will be changed for next year.
[][]For example
=>20AA for AA
=>20BB for BB
=>20CC for CC
And so on..
[][]The last four digits are yearly batch requisition serial number of products manufactured in XX Pharmaceutical Limited, Which (last four digits) will be started from 0001, next batch requisition serial will be started from 0002 and so on.
[][]In every new year, the last four digits (batch requisition serial number) will be started from 0001.
[][]Example for presentation of the Product Batch Number on the Inner Carton, Sample Pack, Label and Shipping Carton:
XX0001
Where
XX stands for year of 20XX
0001 sands for serial number of batch manufactured in year of 20XX.

Batch Numbering System for Water for Injection:

[][]Maintain six characters (six digits are alphanumerical) for batch numbering system.
[][]First digit stands for water for injection
[][]Second and third digits stand for year. It will be changed for next year.
For example
20AA for AA
20BB for BB
20CC for CC
And so on…

[][]The last three digits are yearly batch requisition serial number of water for injection which (last three digits) will be started from 001, next batch requisition serial will be started from 002 and so on.
[][]In every new year, the last three digits (batch requisition serial number) will be started from 001.
[][]Example for presentation of the preprinted ampoule:
WXX001
Where
[][]W stands for Water for injection
[][]XX stands for year of 20XX
[][]001 sands for serial number of batch manufactured in year of 20XX.

Annexure:

Annexure-I: Packaging Material Code

Batch Numbering and Coding System Read More »

Logbook Handling

Logbook , Purpose :

Logbook , The purpose of this SOP is to describe the procedure for issuance and control of logbooks authorized to use GMP related activities.

Logbook , Scope :

This procedure is applicable for all departments at XX Pharmaceuticals Limited (Both General and Sterile Block).

Definitions / Abbreviation:

[][]Logbook: A bound book, which contains preprinted serially page no. and preprinted pages as per the respective SOP’s requirement.

Responsibilities:

[][]The roles and responsibility is as follows:

Quality Assurance Personnel

[][]To issue as per SOP.
[][]To close the completed one.

Concerned Department

[][]To write raw data in it as per defined procedure
[][]To maintain it properly
[][]To submit the completed book.

Manager, Quality Assurance

[][]Approval of the SOP.
[][]To ensure that the implementation of the system as per SOP.

Procedure:

Concerned department shall prepare it for equipment/instrument used in their department. It will be issued by Quality Assurance.

Issue of Log book:

[][]Concerned department shall raise logbook issuance request (Annexure–I) for authorization of it to Quality Assurance.
[][]Quality Assurance shall assign Reference number to new logbook as given below.
e.g. PRO/1
Where
=>PRO is the department code of Production (General)
=>/ is the separator
=>1 is the sequential number of log book
=>Next logbook number shall be 2, 3, 4………and so on.
=>The code of each department is given below.

Department /Code

[][]Production (General)/PRO
[][]Production (Sterile)/C-PRO
[][]Packaging (General)/PKG
[][]Packaging (Sterile)/C-PKG
[][]Warehouse (General)/WH
[][]Warehouse (Sterile)/C-WH
[][]Quality Assurance (General)/QCOM
[][]Quality Assurance (Sterile)/C-QCOM
[][]Quality Control (General)/QC
[][]Quality Control (Sterile)/C-QC
[][]Microbiology (General)/MICRO

Quality Assurance will prepare the front cover of log book (Annexure-III) with unique Reference number.

Review of the log books:

[][] It will be periodically reviewed by the departmental head make an initial.
[][]Concern personnel will ensure proper control and data record during day to day use of logbooks.
[][]After completion of any logbook, a new will be issued by Quality Assurance under same reference no. of the next serial no. of logbook.

Annexure:

Annexure-I: Log book Issuance Request
Annexure-II: Log book Issuance Record
Annexure-III: Log book Front Cover

Logbook Handling Read More »

Internal Audit/Self-Inspection

Internal Audit, Purpose :

Internal Audit, The purpose of this document is to define a systemic, standardized and effective approach of Self Inspection which is performed by personnel within their own functional or departmental unit. This SOP defines the requirements to ensure that self inspection processes are ‘In Place’ and ‘In Use’ which will
help to:
[][]Promote awareness of quality and GMP to avoid quality problems.
[][]Identify risk and manage it as per Risk Management process.
[][]Encourage ownership of continuous improvement actions.

Internal Audit, Scope :

This SOP applies to the all departments which are included in Audit universe (activity of which may affect quality of products of XX Pharmaceuticals Limited). Audit universe is a list of all departments/sections at the site that are to be audited by a Quality function in a calendar year.

Definitions / Abbreviation:

N/A

Responsibilities:

[][]The roles and responsibility is as follows:

Departmental Head/ Manager

[][]Nominate the self inspection team
[][]Prepare the CAPA against Audit findings and agree the CAPA with Quality Compliance.
[][]Ensure the implementation of CAPA
[][]Ensure the completion of JDI activities

Manager, Quality Assurance

[][]In conjunction with Head of Quality Assurance ensure that audit process is ‘in place’ and ‘in use’
[][]Create and maintain department profile
[][]Posting of CAPA in CAPA tracking system and verify follow up & close-out of CAPA
[][]Prepare the self inspection schedule which identifies areas to be inspected.
[][]Review the audit process and present the status in Quality Review Meeting.

Self Inspection Team

[][]Conduct audit against the standard and identify risk
[][]Assess disclosed risk
[][]Prepare audit report and issue it to Head of Quality Assurance

Head of Quality Assurance

[][]Ensure that audit process is ‘in place’ and ‘in use’
[][]Approve the self inspection schedule
[][]Approve the CAPA
[][]Approve changes to an agreed CAPA or date extension request

Procedure:

[][]Self Inspection Frequency:
[][]Frequency of self inspection in every function/department will be twice a year.
[][]It will be recorded in Quality Assurance Department.
[][]Change of frequency of a section/department must be approved by Head of Quality Assurance.

Create and Maintain the Audit Schedule:

[][]Every department/section will conduct checklist based self inspection in twice a year.
[][]Manager, Quality Assurance will prepare a schedule of self inspection and submit it to Head of Quality Assurance for approval by November of each year for implementation in the next year.
[][]The schedule (Annexure I) will contain the following minimum (but not limited to):
=>Name of the area
=>Type of the inspection
=>Systems (QMS) to be audited
=>Month of the audit
=>Name of the Self Inspection team
=>Proposed period (usually 2nd Week of the month)

[][]The approved schedule for the following year will be communicated by Manager, Quality Assurance to all concerned departments by December.
[][]Manager, Quality Assurance will maintain the audit schedule. Every scheduled inspection can be moved within the +/- 10 days time window, however, any change beyond that would require a formal approval of Head of Quality Assurance.
[][]The schedule adherence will be monitored in every Quality Review Meeting.

Preparation for the self inspection

[][]Head of Quality Assurance will assign a self inspection team. A self inspection coordinator will lead the team.
[][]Self Inspection Coordinator must be trained on audit process. The team members must have at least training on the basic cGMP and auditing process.
[][]Self Inspection team will first identify the Department/Sectional SOPs related to specified systems. In addition, the team will review the minimum following (not limited to):
=>Related SOP
=>Department Practices
=>Procedures
=>Worksheets
=>Checklist
=>Departmental CAPAs from CAPA tracking system

Conduct the self inspection

[][]Self Inspection Team will spend sufficient time of a day for the inspection.
[][]The main focus of the team will be to verify whether the site or sectional SOPs are being followed accurately. Self Inspection team will have to ensure ‘In Place’ and ‘In Use’ of the following:
=>Sectional SOP
=>Relevant SOP
=>Procedures (BMR/BPR/Analytical method etc.)
=>Worksheet (Record of Temperature, log books, analytical sheets etc.)
=>Checklist (Line Clearance, machine cleaning, house keeping)
=>Material & Product standards (Specification, storage etc.)

[][]The self inspection team should take a sample of the documents or procedures for those processes or systems running at the time of the self inspection and review it. The review procedure may be as follows:
=>Ask the operator to describe the task/process
=>Check the description against the procedure (SOP/BMR/BPR/Check sheet)
=>Follow/observe the operation/process
=>Verify the records against specified standards

Record and Report findings

[][]The Self Inspection Team must record the non Assurance from the departmental practices and documentation in the specified template (Annexure II).
Based on the associated risks finding will be classified as either
=>Critical
=>Major
=>Minor
=>Note

[][]Team will follow the Annexure III for categorizing the findings.
[][]Self Inspection Team immediately notify critical finding to Department Manager. Operation associated with the critical finding must be stopped immediately until the issue has been resolved.
[][]Self Inspection Coordinator will prepare a full report (Annexure II) detailing all the self-inspection findings within seven (7) working days of the self-inspection and submit it to Head of Quality Assurance.

Propose, Review and Agree the Corrective and Preventive Actions

[][]Head of Quality Assurance will review the self inspection report and send it to Department Manager.
[][]Department Manager will review the inspection report and immediately address the findings which can be corrected by ‘Just Do it (JDI)’. Few example of the JDI is as follow:
=>Immediate correction of line/material labeling errors
=>Operational errors that can be immediately discussed face to face
=>General good housekeeping requirements, such as, emptying of bags, disposal of waste box, and clearing and tidying of the area.
[][]The JDI action implementation date is to be documented in the report (Annexure II).
[][]Department Manager will prepare an action plan (CAPA) for the findings which require more than 30 days implementing.
[][]Department Manager will forward the report to Manager, Quality Assurance along with CAPA within 4 working days of completing Inspection.
[][]Manager, Quality Assurance will verify that proposed CAPAs would adequately manage the root causes of the identified risk and get it approved by Head of Quality Assurance.
[][]After the approval of CAPAs, Manager, Quality Assurance will formally notify the Department Manager and post all the CAPAs in CAPA tracking system within 2 days where every CAPA has a unique reference number mentioned in the inspection report.
[][]Progress CAPA action to closure
[][]Department Manager will close the CAPA as per target date and inform Manager, Quality Assurance formally with physical evidence (SOP, Validation Report or other as appropriate).
[][]After verifying the evidences Manager, Quality Assurance will close the CAPA in the CAPA tracking system.
[][]For any date extension, approval is to be taken from Head of Quality Assurance before the due date.
[][]In every Quality Review Meeting, CAPA status will be reviewed

Annexure:

Annexure-I: Self Inspection Schedule
Annexure-II: Self Inspection Report
Annexure-III: Classification of findings

Checklist for Internal Audit/Self-Inspection

1.Self Inspection Checklist for Quality Control
2.Self-Inspection Checklist for Production _ Packaging Operation
3.Self Inspection Checklist for Quality Compliance
4.Self-Inspection Checklist for Warehouse

Internal Audit/Self-Inspection Read More »

Source Approval of Raw Materials & Packaging Materials

Source Approval, Purpose :

Source Approval, The purpose of this SOP is to describe the procedure for selection, approval of new vendors / sources for raw materials, packaging materials and evaluation of existing ones.

Source Approval, Scope :

This SOP is applicable to all vendors / sources for raw materials, packaging materials which may have an impact on product quality manufactured by XX Pharmaceuticals Limited. This SOP is applicable for both General and Sterile block of XX Pharmaceutical Limited.

Definitions / Abbreviation:

[][]Vendor: A vendor, or a supplier, is an enterprise in the supply chain that contributes goods and services available to companies or consumers. A vendor can operate both as the supplier of goods (seller) and the manufacturer. Generally, a supply chain vendor manufactures inventory/stock items and sells them to the next link in the chain. Today, the terms refers to a supplier of any good or service.
[][]SOP – Standard Operating Procedure
[][]PD – Product Development
[][]QA – Quality Assurance
[][]QC – Quality Control
[][]SCD – Supply Chain Department
[][]COA – Certificate Of Analysis
[][]API – Active Pharmaceutical Ingredient
[][]MSDS – Material Safety Data Sheet
[][]TSE – Transmissible Spongiform Encephalopathy
[][]BSE – Bovine Spongiform Encephalopathy

Responsibilities: Source Approval

The roles and responsibility is as follows:

Executive, PMD

[][]To inform PD, QA and supply chain department about new product with expected production forecast.

Executive, PD

[][]To raise requisition for any new materials required for new product development with PD trial quantity and forward to supply chain department.

Manager, Supply Chain

[][]Sourcing of raw and packaging materials from vendors and to initiate Vendor approval form.
[][]To collect documents as required.
[][]To procure raw materials and packaging materials from approved sources.

Executive, QC

[][]To analyze the source samples from new or existing vendor including raw materials.
[][]To prepare and review of approved source list for raw materials, packaging materials.
[][]Vendor rating.

Executive, Quality Assurance

[][]Evaluation of vendor documents.
[][]Preparation of vendor audit schedule.

Manager, Quality Assurance

[][]Approval/not approval of vendor.

Procedure:

The following procedure is to be followed for procurement from a new source or vendor.

Required Document

[][]To evaluate raw materials vendor following document are required
[][]Duly filled Vendor Approval Questionnaire
[][]Duly filled Vendor Approval form
[][]Certificate of Analysis (COA)
[][]Method of Analysis (in case of non-compendial method)
[][]Stability data (both accelerated and long term) justifying shelf-life
[][]Material Safety Data Sheet (MSDS)
[][]Working Standard of Active Material with COA

[][]Manager, Supply Chain forwards the sample along with these documents to Quality Control Department.
[][]To evaluate primary packaging material vendor following document are required. For secondary packaging material vendor 1st four are required.
=>Duly filled Vendor Approval Questionnaire
=>Duly filled Vendor Approval form
=>Certificate of Analysis
=>Method of Analysis
=>Design and specification
=>TSE/BSE free Certificate
=>Material Safety Data Sheet (MSDS)
=>Certificate of Composition

Approval of new vendor of raw materials:

[][]After getting information about new product with expected production forecast from PMD; PD will sent purchase requisition to supply chain department for procurement of new materials required for PD trial and share necessary information of new product to QC for preparation of specification.
[][]QC generates draft specifications for new material with the concern of PD. Any in-house specification that should be included on the basis of literature survey or PD requirement. For INN material QC develops specification based on Manufacturer’s COA / specification and PD requirement.
[][]Supply Chain department identify suitable vendors for required material and ask for COA of that specific material to forward to QC. Evaluating manufacturer’s COA, QC will ask for QC test sample (mentioning quantity) from suitable vendors through SCD.

[][]Supply Chain collects QC test sample / PD sample with documents from suitable vendors and then forwards to QC along with filled Vendor Approval Form (as per Annexure- I).
[][]QC receives source sample and documents and makes entry in a register with lab control no., name of material, lot. No., code no., manufacturer, supplier / local agent / indenter, manufacturing date, expiry date, quantity received, received by and date and review documents, if any anomalies observed then inform supplier through SCD.

[][]After testing QC makes entry of analyzed by and date; checked by and date; remarks in that register and shares QC test result of source sample with supplier and SCD.
On the basis of QC test result, SCD can procure PD trial sample of API from selected vendor.
[][]In receipt of PD trial sample of API, QC will arrange test for the same and then forwards PD trial sample to PD for formulation development along with analytical result and filled Vendor Approval Form.
[][]Sr. Executive / Asst. Manager, QC will put his comment on Vendor Approval Form after QC test of PD trial sample of API and QC test sample of excipients.
[][]On the basis of PD trial and stability report of formulated product with PD trial sample, PD will put his comment on Vendor Approval Form, then forward to Quality Assurance Department.
[][]Quality Assurance reviews the analytical data, PD trial report, available relevant documents and records and then put comment on Vendor Approval Form.
[][]If all reports comply the requirements, Manager, QA will grant approval for purchase of one initial consignment and the source will be included in approved source list as Category B (New sources on trial). If requirement does not comply, Manager, QA shall not approve the sample for procurement from that vendor.
[][]Product analytical results of at least three consecutive commercial batches to be evaluated to approve the supplier as Category A (Established source).

Approval of new vendor of packaging materials:

[][]For packaging materials other than printed one, Supply Chain collects source sample /Machine trial sample (Foil/Film -5 kg; Other materials -50 pcs or as per requirement) and required documents including Vendor approval questionnaire from supplier and then forward to QC along with filled Vendor Approval Form.
[][]QC receives source sample and documents and makes entry in a packaging material vendor sample register with lab control no., name of material, lot. No., code no., manufacturer, supplier / local agent / indenter, manufacturing date (where applicable), expiry date (where applicable), quantity received, received by and date.
[][]After testing, QC forwards machine trial sample along with machine trail report form (Annexure-IV) to production for machine trial.
[][]If the machine trial report is satisfactory, PD will arrange 6 months stability study for all primary packaging materials.
[][]Manager, QA will grant approval for purchase of one initial consignment on the basis of QC test result, machine trial report and stability study and the source will be included in approved source list as Category B (New sources on trial).
[][] If requirement does not comply, Manager, QA shall not approve the sample for procurement from that vendor. SCD can procure commercial sample after vendor approval.
[][]The analytical results of at least three consecutive commercial batches to be evaluated to approve the supplier as Category A (Established source).

Vendor Rating:

[][]A cross functional team shall jointly perform the vendor rating which consist of QC, SCD & QCOM
[][]To evaluate the performance of vendor Quality rating, Delivery rating, Price rating and Vendor rating shall be calculated in the following way.

Carry out the incoming inspection, analysis and calculate the ‘Quality rating’ as follows:

QR = Q1 + X1Q2 + X2Q3/Q

Where,
Q = Quantity Received
Q1 = Quantity Accepted without any comment/ problem
Q2 = Quantity Accepted with deviation; X1 = 0.7 (factor for deviation)
Q3 = Quantity Accepted with rectification; X2 = 0.5 (factor for rectification)

[][]Send the Quality Rating to Manager, SCM.

[][]SCM shall carry out the Delivery rating and Price rating as follows

Calculation of Delivery Rating of Vendor:

DR = q1 + 0.5q2/q

Where,
q = Quantity Ordered
q1 = Quantity received as on before time
q2 = Quantity received beyond due date

Calculation of Price Rating of Vendor:

PR = Minimum quotation received/ Price paid

[][]After completion of Delivery rating and Price rating, Executive, QCOM shall calculate and classify the vendor rating and approved by Head of QA.
Calculation of Vendor rating: VR = (0.5 QR + 0.3 DR + 0.2 PR) X 100

Classification of the Vendor Rating:

VR = 100 Good
90 ≤ VR < 100 Satisfactory
50 ≤ VR < 90 Deficient
VR < 50 Rejected

[][]Delete the vendor from “Approved Vendor list” when the level reaches “Rejected”.
[][]Finalize the list and forwarded the same to Quality Assurance Department for approval. Quality Assurance shall then circulate the “Approved Vendor/ Supplier list” to relevant department.
[][]The records of “Vendor Rating” will be kept for a minimum period of 3 years and the evaluation will be done at 3 years interval.

Procedure for exclusion of vendor from approved vendor’s list:

[][]The vendor shall be disqualified and removed from the approved vendor’s list for following reasons during regular assessment.
[][]If consecutive three consignments of material fail to comply the specifications or if the approval rate is below 70%.
[][]Three out of ten consignments fail to comply the specification.
[][]The delivery schedule is not met for 40% of supplies.

Corrective and preventive action:

[][]The vendor shall be made aware of the reasons for his exclusion and shall agree improvement action plans.
[][]The vendor, who has been excluded from the approved vendor list, may be included again by taking following corrective action and preventive actions.
[][]Manager, Quality Assurance or his representatives shall conduct facility audit of the vendor in order to ensure that quality system exists in the organization.
[][]Carry out the discussion on other non-quality issues like delivery schedule and rate etc.
[][]After Satisfactory outcome of all above points the vendor shall be approved as per the new vendor evaluation procedure.

Auditing

[][]Supplier audits will be conducted by experienced auditors nominated by Manager, Quality Assurance. Auditors will have experience/training in GMP auditing.
[][]Pre-audit meeting: A meeting of Manager, Quality Assurance, auditors and any other relevant personnel such as Procurement/ Technical expert shall be conducted 2 weeks prior to the audit.
[][]This meeting shall review all information available and any previous audit recommendations (in case it is done earlier) and status, complaints raised, number of deliveries since the last audit and any issues.
[][]The audit report (Annexure-V Audit Report Template) shall be finalized within 4 weeks after the audit and sent to SCM for forwarding it to the supplier/vendor with an advice that the supplier/vendor will give their feedback within 1 month of receipt of the report and prepare an action plan to close the gaps identified during the audit.

[][]Reference No. for Audit Report shall be as
AR/RM or PM/20xx-1
Where-
=>AR represents audit report
=>RM represents raw materials
=>PM represents packaging materials
=>20xx represents auditing year
=>1 represents sequential number
[][]SCM will follow up with the Supplier/vendor on the progress of recommended actions and any response or follow up correspondence shall be filed with the audit report in the appropriate supplier file.
[][]When a supplier/vendor is audited for the first time, a follow up audit should be conducted as per agreed time line with the supplier for the confirmation of the status of the Supplier.
[][]A supplier quality audit shall be performed at every 3 years interval which based on supplier’s documentations followed by desktop audit.

Supplier Status

[][]Updated approved source list must be maintained / amended / updated by Quality Control, that will be reviewed in every 6 months accordingly. Copy of approved source list will be shared to SCD, Warehouse, Production, Quality Assurance department. The list will hold two categories of suppliers:
=>Category B – New supplier/vendor under study.
=>Category A – Supplier/vendor having 3 consecutive satisfactory supplies
[][]If a supplier’s status is downgraded due to a quality problem, an unsatisfactory audit or any other issues, immediate action must be taken. The following actions must be considered:
=>Inform Manager, Quality Assurance
=>Amend Suppliers List
=>Source an alternative supplier on urgent basis
=>Review retrospective impacts on product quality

Supplier Files

[][]All related supplier approval documentation must be collated and filed in the appropriate supplier file. This should include the following where relevant:
=>Quality assessment questionnaire
=>Audit Checklist, Audit Report and Audit Summary Report
=>Response from the supplier
=>Relevant documents, i.e, Deviation Reports or Customer Complaint forms
=>Any other correspondence

Annexure: Source Approval

Annexure-I: Vendor Approval Form
Annexure-II: Vendor approval questionnaire – Raw materials
Annexure-III: Vendor approval questionnaire – Packaging materials
Annexure-IV: Machine trial report form
Annexure-V: Vendor Audit Report Template
Annexure-VI: Vendor Rating Form

Source Approval of Raw Materials & Packaging Materials Read More »

Deviation Procedure

What is Deviation?

A deviation in many industrial contexts is a deviation from an established, accepted process, procedure, guideline, specification, or standard. Especially in the pharmaceutical industry, deviations can occur at many stages, including development, manufacturing, labeling, packaging, sampling, testing, storage, distribution, and other complex industrial processes.

It is important to note that the definition of deviation may vary slightly depending on the regulatory body overseeing a company’s operations and the specific requirements governing these processes. These different definitions reflect the complex and highly regulated nature of the pharmaceutical industry, where strict compliance with standards is critical.

The International Council for Harmonization of Pharmaceuticals for Human Use (ICH) defines a deviation as a deviation from approved guidelines or established standards, as described in the ICH Q7 Good Manufacturing Practices (GMP) Guidelines for Active Pharmaceutical Ingredients. This highlights ICH’s commitment to ensuring consistency and reliability in pharmaceutical manufacturing practices.

For example, the International Organization for Standardization (ISO) provides a comprehensive definition in the context of quality management systems under ISO 9001:2015. Deviation here refers to the positive or negative effects resulting from deviations from expected or established values. This highlights ISO’s emphasis on maintaining a strong quality management framework.

Within the U.S. Food and Drug Administration (FDA), which plays a central role in drug regulation, it defines deviations from quality management system guidelines for the pharmaceutical industry and current good manufacturing practice (CGMP) regulations. External falls do not fall within the limits or do not meet certain requirements. The FDA’s rigorous standards emphasize the importance of maintaining high levels of quality and safety throughout the drug manufacturing chain.

Basically, deviations in the pharmaceutical industry are perceived not only as deviations from established standards, but also as events that can lead to positive or negative consequences. The variety of definitions provided by different regulatory authorities highlights the importance of a concise understanding of deviations to maintain the integrity and safety of pharmaceutical processes and promote regulatory compliance.

Type of Deviation

Deviation can be classified mainly Two types
  • Planned Deviation
  • Unplanned Deviation
Based on risk then it can be classified as
  • Critical Deviation
  • Major Deviation
  • Minor Deviation
  • Incident

Deviation, Purpose :

  • Deviation, This procedure provides a standardized process for handling quality related unplanned events & GMP deviation.
  • To develop a systemic approach for handling quality related failures & GMP deviation.
  • To ensure that deviations are recorded and assessed for their impact on product quality, patient safety and regulatory compliance.
  • Action is taken to address any immediate risks, including impact on other batches and products.
  • Investigation requirements and identification of any corrective and preventive actions (CAPAs) are based upon the level of risk.

Deviation, Scope :

The process applies to all quality & GMP failures and unplanned deviations in General Block and Sterile Block of XX Pharmaceuticals Ltd. which are related (but not limited) to the following:

  • Manufacturing Processes/operations (manufacturing, packing, testing, distribution), yield and reconciliation limit.
  • Facilities including equipment, utilities failure and critical instrument calibration failure.
  • Equipment/machinery breakdown during operation.
  • Failure of PLC based system that directly affects product quality
  • Equipment and facility Operation outside validated ranges
  • Storage condition of raw and packing materials
  • Storage period of bulk product
  • Documentation error affecting product quality.
  • Product standards
  • Standard Operating Procedure
  • Work Instructions including validation protocols.
  • Incidents impacting GMP & product or material quality
  • The process does not apply to the following as these are managed separately by individual SOPs:
  • Out of Specifications (OOS/Atypical) analytical and microbiological results.
  • Environmental action and alert limit excursions, where these have arisen as a result of laboratory testing
  • Stability failures/ stability protocols
  • Customer complaints and adverse events
  • Equipment/machinery breakdown during routine maintenance
  • Out of calibration noticed at the time of calibration activity
  • Recalls
  • Outside of in-process parameter followed by immediate rectification
  • Vendor complaints (On line rejection)
  • Deviations associated with outcome of any non-routine activity or trials.
  • Where actions have been justified, documented and pre-approved by Quality Assurance e.g. via SOP, BMR, BPR, Analytical Method.

Investigation process will be mandatory in the following instances:

  • Major/critical deviation/complaints/significant incidents.
  • OOS
  • Rejection
  • Recall
  • Consecutive 3 time excursions of alert limits.
  • Any incident agreed by management

Definitions / Abbreviation:

Deviation:

Deviation is an unplanned departure from SOPs, methods, specifications, protocols, batch records or other official documentation. A deviation may also be defined as a departure from instructions, processes, process specifications or normal conditions or any departure from good manufacturing practice.

Planned Deviation:

A deviation or change to test method, laboratory or manufacturing procedures that has been planned and approved before the process conducted as a part of temporary change. Planned Deviation should be reported before the process. Planned deviations will be handled through the QA approved change control procedures.

The deviations are classified as critical, major and minor. The definition is as under

Critical Deviation

A critical GMP deviation/exception could endanger product safety and/or efficacy due to the use of an inadequate process or controls. Failure of detection would lead to a product recall/withdrawal/serious complaint.

Major Deviation

A major GMP deviation/exception does not directly influence product safety and efficacy but may require remedial action before approval of manufacture or continue to manufacture. This could lead to serious regulatory compliance implications, Major cost to business or adverse comments from inspectors.

Minor Deviation

A minor GMP deviation/exception does not directly influence product safety and efficacy but may have an impact on cosmetic quality. This also includes minor document irregularities. This could lead to Cosmetic pack complaint or Late orders.

Investigation-

It is the process of identifying the cause of deviations/unwanted incidents. Purpose of Investigations are:
=>Identify
=>Correct
=>Evaluate product impact / disposition
=>Prevent similar events from happening in the future;

Responsibilities:

The roles and responsibility is as follows:

Observer(who observed the incident)

To notify Section in Charge/Departmental Manager immediately after observing any event.

Initiator (Section in Charge/ Dept. Manager)

  • To take any possible immediate actions to contain the event.
  • To record the event in log book and batch document.
  • To fill the “Deviation and Investigation Form” immediately after “On the spot investigation”.
  • To escalate the event to Functional Head

Functional Head or his designee

  • To decide in conjunction with Quality Compliance whether the incident is deviation or not and, if confirmed, any subsequent investigation required.
  • To ensure proper recording of deviation
  • To carry out initial assessment of the incident after collection of required data and ensure recording in batch document.
  • To decide on the requirement of assembling investigation team (in consultation with Manager Quality Assurance) for further investigation to find out root
  • cause and define recommendation.
  • To invoke CAPA process if require by forming CAPA team.

Head of Quality Compliance or his designee

  • Maintain the register for deviation & investigation
  • To provide the guidance on whether the incident is a deviation or not
  • To participate the initial assessment & follow up of remedial action.
  • To assess the severity of deviation and define criticality.

Manager, Quality Assurance

  • To approve the initial assessment & remedial action.
  • To approve the deviation & investigation
  • Investigation Leader (Any competent person nominated by Functional Head)
  • To lead the investigation and find out the root cause
  • To complete investigation within stipulated time.

Procedure: (Management of deviation)

Observation and notification of Deviation:

  • If any staff observes any of the incidents (described in scope), he/she will immediately notify the incident to Section in Charge/Departmental Manager.
  • Section in Charge/Departmental Manager will immediately conduct initial impact assessment and take any remedial action. e.g.
  • Stopping operation to prevent production of further faulty product,
  • Segregating material that may be affected.
  • Immediate correction
  • Departmental Manager will record the detail incident in the associated log book and/or BMR/BPR in a timely manner. The record must be clear, concise, and traceable and include all relevant details (e.g. time, date and nature of the incident, name of the observer).
  • Departmental Manager will immediately escalate the event to Functional Head (Head of Department)
  • Departmental Manager in consultation with Functional Head will determine whether the incident constitutes a deviation based on its potential impact on material/product quality or regulatory compliance.
  • For the ease of detection they can take the guidance of scopes . If there is any doubt as to the potential impact, the event will be treated as a deviation.

Recording of Deviation

  1. If it is determined that the incident constitutes a deviation, then the Departmental Manager will record all the information in section A of Deviation Report Form (Annexure-I).
  2. The Functional Head will decide
    =>if the production/operation should be stopped or not
    =>With proper authorization & justification allow the product to proceed.
  3. Departmental Manager will record the decision in Deviation Report Form. Departmental Manager will assign a unique reference number (obtained from Quality Compliance Department) to the Deviation Form.
  4. The number will be derived from Deviation register (Annexure-II). Deviation register will be maintained in both hard copy and Microsoft Excel based spreadsheet.
  • Deviation Form number shall be alphanumeric system containing 11 characters. Numbering breakdown is as follows: DRyy/Area code/xxx.
    Area Code is as follows:
    =>General Block : GB
    =>Sterile Block : CB
    =>For example: DRyy/GB/001.
  • The first two alphabets shall stand for Deviation Report
  • Next two numeric characters shall stand for year code 16 shall denote year 20xx.
  • Next character is slash (/), followed by two capital letter stands for area code of General Block at XX Pharmaceuticals Ltd.
  • Next character is slash (/), followed by three numerical shall stand for serial number, which shall start every year from 001. For example first Deviation Report no DRyy/GB/001 and second DRyy/GB/002, third DRyy/GB/003 and so on.
  • In case of Sterile block, Deviation Report number shall be DRyy/CB/001 and so on. Two capital letter CB stands for area code of Sterile block at XX Pharmaceuticals Ltd.
  • The number will be unique; if proposal is withdrawn/ rejected the same number will never be used again.
  • If incident implicates a batch then the unique reference number is to be recorded in related batch documents.
  • The deviation must be recorded with the following information:
    =>A unique reference number
    =>The date on which the deviation was first identified
    =>Name of person recording the deviation
    =>The identity (Batch No.) of any batch or batches implicated by the deviation
    =>A description of the deviation
    =>The identity of any process, equipment or system implicated by the deviation
    =>Initial actions taken
  • Functional Head will ensure that all relevant data/information is gathered to allow an initial assessment of the deviation.

Assessment of risk

  • Departmental Manager along with Quality Compliance Manager and any other expert in this field (i.e. Engineering Manager/Compliance Manager/Quality Control Manager/Microbiology Manager) will assess the impact of the deviation considering the following issues (section B in Annexure-I) and will propose a remedial action within 1 day of recording the deviation:
    =>Patient/customer risk & product efficacy
    =>Quality Implication (strength, identity, purity and stability)
    =>Effect on regulatory compliance
    =>Impact on any batch (es) immediately affected.
    =>Impact on any other batch(es)/processes which may be affected, considering any other areas/sites
    =>Current location and status of any implicated batch (whether the implicated batch is on the market or within XX’s control).
    =>Any remedial action taken/required
    =>Detection point of failure (detected by chance/detected during checking/detected at the point of error)
  • The initial assessment may result in wider implications than originally identified e.g. more batches than just the batch the deviation was detected on.
  • Quality Compliance Manager will assess the risk of deviation considering the above and categorize or prioritize the event as:
    =>Critical
    =>Major
    =>Minor
  • The aim of this categorizations are to determine the:
    =>Priority for resolving the deviation
    =>The time scale for addressing the deviation
  • Communication details & person to whom incident is to be communicated (if required).
  • Non conformity which is not detected through any standard process or detected only by chance will be treated as critical/major deviation. In all cases where the deviation relates to, or may implicate product already in the market place, will also be treated as critical.
  • Critical deviation will be immediately escalated to Head of Quality Assurance. He/she will communicate the matter to Managing Director and other stakeholders accordingly.
  • If requires Head of Quality Assurance will communicate the matters to Contact Manufacturer and collect their recommendation for the correction of the product.
  • Quality Compliance Manager in consultation with other Technical /Quality Experts will provide a recommendation/ remedial action to ensure that any adverse condition arising from the deviation are controlled and pose no further risk.
  • Determine Root Cause Investigation Requirements
  • Manager, Quality Assurance in consultation with Head of department will assess whether root cause investigation is required.
  • Root cause investigation is required where there is a risk to patient/ customer safety or serious regulatory compliance issues assigned through severity assessment in section 7.3.3. . For example:
    =>The severity of deviation is Critical/Major.
    =>Remedial actions have not fully mitigated the risk
    =>The deviation is a recurrence
  • If root cause investigation is not required, AGM, Quality Assurance will give a rationale and the deviation process can be progressed toward to point close.
Perform root cause investigation
  • The investigation will be conducted as per process described in previous point
  • The key output from this investigation will be a statement of actual root cause or most probable cause of the deviation and recommendation with timescale to address root causes.
  • After completion of the investigation, a copy of the investigation will be attached with the deviation report.
Identify Corrective and Preventive Action (CAPA)
  • On the basis of the severity of investigation, the Head of department jointly with AGM, Quality Assurance & Quality Compliance Manager will decide on the requirement to invoke CAPA process and develop Corrective and Preventive action to address the root cause identified in previous section and prevents recurrence of happening in future.
  • In case of CAPA process not applicable, this process should be closed with the comments and authorization by Manager, Quality Assurance.
CAPA will not be required if AGM, Quality Assurance confirms the followings:

=>If the deviation categorized as minor.
=>Implementation of identified CAPA is no longer applicable-for instance the root cause relates to equipment that has been replaced, or is planned to be replaced as part of an existing approved action.
=>Remedial actions taken address the root cause
=>The risk related to recurrence is low

If CAPA process is applicable, Head of Department will identify competent person to be a CAPA Leader to implement the CAPA objectives. CAPA leader will follow the formal CAPA process as per SOP: Corrective and Preventive Action Handling Procedure.
The Deviation Handling process will be closed when the CAPA triggered from this process is approved.

Handling of deviation implicated batch

  • No batch will be released until the deviation is closed.
  • All actions required to assure the quality of any impacted batches must be identified, agreed by the Quality Compliance, and completed prior to batch release
  • The copy of closed deviation report and investigation report must be filed with associated batch document (if implicated with any batch) during batch release.
  • Manager, Quality Assurance has ultimate authority to take decision on progression or release after completion of all actions.
  • Time limit, Follow up and Management Review
  • If investigation is not required deviation is to be closed within 7 days of initiation.
  • For deviation associated with investigation will be closed within 15 days of deviation initiation.
  • Initiator will coordinate the implementation of recommended/remedial action within agreed timeframe.
  • Quality Compliance will ensure that deviation has been effectively closed within the agreed timeframe. After closing Quality Compliance Manager will update the deviation tracker & register and archive the hard copy of original deviation form.
  • A copy to be provided to attach with the relevant document such as validation protocol.

Handling of Investigation:

  • Investigation will be triggered to address any unexpected discrepancy from different interfaces:
    =>Critical/Major Deviation
    =>Critical/Major market compliant
    =>Any GMP Quality incident
    =>Recall, reject and Reprocess
  • Functional Head (Head of Department) and Head of Quality Assurance will jointly decide where the investigation is required.
  • If root cause investigation is required, the Functional Head(Head of Department) will check the criticality of incident (critical/major/minor) as defined in the interface to determine the scale of investigation e.g. extent of investigation team, amount of structure for problem solving, level of documentation, requirement of resources or capital budget etc.
  • The Functional Head (Head of Department) will nominate an Investigation Leader & other members of investigation team who will conduct the investigation.
  • Generally Departmental Manager of impacted area will be selected as Investigation leader.
  • For the complex investigation, team should be cross functional composing the members of Quality Unit, Engineering and any other Technical Experts.
  • The team will take a unique reference number of investigation from Quality Compliance Office. Quality Compliance Officer will log the details in the investigation register (Annexure- IV).
  • All investigation will be conducted through this form (Annexure-III: Template of an investigation report).
  • Investigation Report numbers are assigned by Quality Compliance. Investigation Report number shall be alphanumeric system containing 11 characters. Numbering breakdown is as follows: IRyy/Area code/xxx.
    Area Code is as follows:
    =>General Block : GB
    =>Sterile Block : CB
    For example: IR16/GB/001.
  • The first two alphabets shall stand for Investigation Report
  • Next two numeric characters shall stand for year code 16 shall denote year 2016.
  • Next character is slash (/), followed by two capital letter stands for area code of General Block at XX Pharmaceuticals Ltd.
  • Next character is slash (/), followed by three numerical shall stand for serial number, which shall start every year from 001. For example first Investigation Report no IR16/GB/001 and second IR16/GB/002, third IR16/GB/003 and so on.
  • In case of Sterile block, Investigation Report number shall be IR 16/CB/001 and so on. Two capital letter CB stands for area code of Sterile block at XX Pharmaceuticals Ltd.
  • The number will be unique; if proposal is withdrawn/ rejected the same number will never be used again.
  • The team will collate the facts and data in consultation with relevant personnel and document.
  • Investigation team will prepare a report of investigation within the time line. All steps & findings will be recorded in the report.
  • The key aim of the investigation is to identify the root cause or most probable cause of the deviation incident.
  • Where the identification of actual or most probable root cause is not possible, the risk associated with uncertainty is to be assessed & recoded with adequate control.
  • The maximum time for the identification of root cause is 15 working days after recording of incident.
  • Investigation report will be approved by Functional Head (Head of Department) and Manager, Quality Assurance.

 

What challenges might arise when dealing with Deviation Management?”

Managing deviations within an organizational framework poses a myriad of challenges, demanding a nuanced approach to navigate these intricacies effectively. The intricate realm of deviation management encompasses the intricate task of addressing situations where the realized performance or outcomes veer off course from the meticulously laid out plans or anticipated expectations. As organizations grapple with this multifaceted process, several challenges may emerge, each requiring careful consideration and strategic resolution.

One of the primary challenges encountered in the domain of deviation management is the inherent complexity associated with identifying the root causes of deviations. Organizations often find themselves immersed in a labyrinth of factors contributing to these deviations, ranging from internal processes and external influences to unforeseen circumstances. Unraveling these complexities demands a thorough investigation and a keen understanding of the interplay between various variables, enabling organizations to pinpoint the factors triggering deviations accurately.

Moreover, deviation management is intricately linked with the need for efficient communication channels within an organization. The timely and transparent dissemination of information pertaining to deviations is paramount, as it empowers stakeholders at all levels to make informed decisions. Inadequate communication may exacerbate the impact of deviations, leading to misunderstandings, delays, and a potential erosion of trust within the organizational fabric.

In addition, the challenge of striking a balance between corrective actions and the preservation of operational efficiency looms large. Organizations must devise strategies that not only rectify the immediate deviations but also do so in a manner that minimizes disruptions to ongoing operations. The intricacies of this balancing act require a holistic approach that considers the long-term implications of corrective measures on the overall organizational performance.

Furthermore, the globalized and interconnected nature of modern businesses introduces an additional layer of complexity to deviation management. Organizations often operate within a network of suppliers, partners, and stakeholders, each contributing to the intricate web of dependencies. Managing deviations becomes a collaborative effort, necessitating effective coordination and cooperation among various entities to address and mitigate the ripple effects across the entire ecosystem.

In conclusion, the challenges associated with deviation management underscore the need for organizations to cultivate resilience, adaptability, and a proactive approach. Addressing these challenges requires a comprehensive understanding of the underlying dynamics, coupled with strategic initiatives aimed at fostering a culture of continuous improvement and proactive deviation anticipation. Successfully navigating these challenges not only ensures smoother operations but also positions organizations to thrive in an ever-evolving business landscape.

1. Identification and Detection of Deviations:

Navigating complexity poses a formidable challenge when it comes to recognizing deviations, particularly within intricate systems or processes characterized by the interplay of numerous factors influencing performance outcomes. The intricacies inherent in such environments demand a heightened level of scrutiny and analytical precision to successfully pinpoint variations from the norm.

The critical importance of timeliness in the detection of deviations cannot be overstated. Swift and accurate identification is paramount, as any delay in the recognition of anomalies may result in protracted issues and expose the system or process to potential negative impacts. The urgency in timely detection stems from the need to address deviations swiftly, thereby preventing the escalation of problems and mitigating any adverse consequences that might ensue.

Moreover, the time-sensitive nature of detecting deviations underscores the significance of establishing efficient monitoring mechanisms and implementing proactive measures. A proactive approach involves anticipating potential deviations, implementing real-time monitoring, and deploying predictive analytics to foresee issues before they manifest fully. This forward-thinking strategy not only minimizes the risk of prolonged disruptions but also allows for the implementation of corrective actions before deviations escalate into critical problems.

In the realm of complexity, it becomes imperative to foster a comprehensive understanding of the intricate web of factors influencing performance outcomes. This entails not only identifying deviations when they occur but also gaining insights into the underlying dynamics that contribute to such variations. An in-depth comprehension of the contributing factors enables a more holistic approach to deviation detection, enhancing the capacity to discern subtle deviations that might otherwise go unnoticed.

In conclusion, the challenges presented by complexity necessitate a multifaceted approach to the identification of deviations. Timeliness emerges as a crucial factor, emphasizing the need for swift detection to prevent prolonged issues and potential negative impacts. Implementing proactive measures and gaining a profound understanding of the intricate interdependencies within complex systems further fortify the capability to navigate and manage deviations effectively.

2. Root Cause Analysis:

In order to effectively identify the underlying reasons for deviations, a profound depth of analysis is imperative. This entails delving deep into the intricacies of the situation, as superficial investigations often yield only temporary solutions, failing to tackle the root causes that perpetuate issues over time.

The significance of resource intensity becomes evident when undertaking comprehensive root cause analyses. Such endeavors demand considerable resources, not just in terms of time but also requiring a wealth of expertise. Thoroughly examining the multifaceted aspects of a problem necessitates a commitment of substantial time and the involvement of individuals with specialized knowledge in the relevant domains.

Delving into the depth of analysis implies a meticulous examination of various factors contributing to deviations. This involves scrutinizing processes, systems, and interactions at a granular level to uncover the fundamental sources of problems. It goes beyond addressing symptoms on the surface and aims at understanding the intricacies that give rise to deviations, thereby enabling the development of more robust and sustainable solutions.

Furthermore, the resource intensity associated with comprehensive root cause analyses extends beyond temporal considerations. It involves tapping into a reservoir of expertise, leveraging the insights and knowledge of individuals who possess a nuanced understanding of the subject matter. This collaborative effort ensures a holistic examination of the issue, fostering a comprehensive perspective that facilitates the identification and rectification of root causes.

The depth of analysis and resource intensity are intertwined aspects that underscore the importance of adopting a strategic and well-organized approach to problem-solving. By investing the necessary time and expertise, organizations can move beyond superficial fixes and address the core issues that may be impeding their efficiency and effectiveness. This proactive stance not only promotes long-term sustainability but also cultivates a culture of continuous improvement within the organizational framework.

3. Communication and Reporting:

Transparency stands as a cornerstone in any organizational framework, emphasizing the critical importance of fostering open communication regarding deviations. The significance lies in the fact that challenges can swiftly emerge in the absence of transparency, given that stakeholders rely on comprehensive information to make well-informed decisions.

In the realm of effective reporting, the imperative is to establish a robust system that not only highlights deviations but also ensures clarity, conciseness, and ease of understanding. Crafting such a reporting mechanism poses a noteworthy challenge, as it requires a careful balance between providing detailed insights and presenting information in a manner that is easily comprehensible to a diverse audience. This calls for the implementation of streamlined processes that not only capture the intricacies of deviations but also translate them into a format that resonates with stakeholders at various levels within the organization.

Moreover, effective reporting transcends mere documentation; it serves as a strategic tool for organizational improvement. By investing in a reporting system that goes beyond the perfunctory and delves into the root causes of deviations, organizations can uncover valuable insights. These insights, in turn, pave the way for proactive problem-solving and the implementation of preventative measures, fostering a culture of continuous improvement.

In essence, the synergy between transparency and effective reporting forms a formidable foundation for organizational resilience and adaptability. It is not just about acknowledging deviations but also about leveraging them as opportunities for growth and refinement. As organizations navigate the complexities of their environments, embracing a culture that places a premium on transparent communication and meticulous reporting becomes pivotal in steering towards sustainable success.

4.Decision-Making:

Navigating the Decision-Making Tightrope: Striking the right chord in determining the suitable course of action to rectify deviations necessitates a nuanced and intricate balancing act. It requires a careful assessment that takes into account the urgency of the situation, the potential ripple effects, and the array of resources at our disposal. This process is akin to walking a tightrope, where precision and equilibrium are crucial.

Urgency Consideration: Delving deeper into the intricacies, the urgency of the situation stands as a pivotal factor. Decisions made must be time-sensitive, recognizing the immediacy of the deviations at hand. This involves evaluating the degree of impact and the potential consequences of delayed action, emphasizing the need for a swift and strategic response.

Impact Analysis: The ripple effects stemming from addressing deviations should be meticulously analyzed. Understanding the potential impacts on various facets of the organization allows for a comprehensive decision-making process. This involves foreseeing both short-term repercussions and long-term consequences, ensuring that the chosen course of action aligns with overarching organizational goals.

Resource Evaluation: The availability and allocation of resources play a significant role in the decision-making process. A thorough examination of the resources at hand is imperative, encompassing financial, human, and technological aspects. This evaluation not only aids in determining the feasibility of various courses of action but also ensures optimal resource utilization for maximum efficiency.

Conundrum of Conflicting Priorities: A common challenge emerges when addressing deviations intersects with other organizational priorities. This creates a conundrum, compelling decision-makers to grapple with intricate dilemmas related to resource allocation. In such scenarios, decisions become a delicate juggling act, requiring a keen understanding of organizational priorities and strategic alignment.

Strategic Resource Allocation: The clash of priorities necessitates a strategic approach to resource allocation. Decisions must be guided by a keen awareness of the broader organizational landscape, considering the potential repercussions on other projects or initiatives. This strategic resource allocation involves prioritizing tasks and projects based on their criticality and alignment with overarching organizational objectives.

In essence, the decision-making process in addressing deviations involves a multifaceted examination that encompasses urgency, impact, and resource considerations. Negotiating the complexities of conflicting priorities requires a strategic mindset and a keen understanding of the broader organizational context, ultimately leading to decisions that harmonize with the organization’s overarching goals and priorities.

5. Implementation of Corrective Actions:

Navigating Resistance to Change: The introduction of corrective actions may encounter resistance among employees who have grown accustomed to established processes. This resistance can emanate from a variety of sources, including a fear of the unknown, concerns about job security, or simply a reluctance to step out of one’s comfort zone. It is imperative to recognize that fostering a culture of adaptability is pivotal in overcoming these challenges. Change management, therefore, emerges as a critical component in these scenarios, demanding thoughtful strategies to communicate the benefits of change, address concerns, and ultimately garner support from the workforce.

Cultivating Change Management Strategies: To successfully implement corrective actions, organizations must invest in robust change management strategies. This involves clear communication channels that elucidate the rationale behind the changes, the expected benefits, and the role each employee plays in the transition. Additionally, providing training and support mechanisms can empower employees to embrace the changes confidently. By cultivating a sense of ownership and involvement, organizations can minimize resistance and enhance the likelihood of successful implementation.

Monitoring and Ensuring Effectiveness: The implementation of corrective actions is just the initial phase; ongoing monitoring and follow-up are indispensable for sustained success. Organizations must establish systematic mechanisms to track the effectiveness of the implemented changes, identifying any areas that may require further adjustment. This involves setting up key performance indicators (KPIs) and regularly assessing progress against these benchmarks. Moreover, fostering a culture of continuous improvement ensures that organizations remain agile and responsive to evolving challenges.

Dynamic Attention to Change: The dynamic nature of the business environment necessitates a continuous commitment to monitoring and follow-up. Changes in market conditions, technological advancements, or internal dynamics may require organizations to adapt and refine their corrective actions. Therefore, a proactive approach to monitoring, coupled with an agile response mechanism, enables organizations to stay ahead of potential challenges and capitalize on emerging opportunities.

Employee Engagement in the Monitoring Process: Actively involving employees in the monitoring and follow-up process is a crucial aspect of ensuring sustained success. Soliciting feedback, conducting regular check-ins, and creating a feedback loop where employees can express concerns or suggest improvements fosters a sense of inclusivity. This not only enhances the effectiveness of corrective actions but also strengthens the overall organizational culture, promoting a collaborative and adaptive ethos.

In conclusion, addressing resistance to change and ensuring the effectiveness of corrective actions are multifaceted challenges that demand a comprehensive approach. By prioritizing change management strategies, implementing robust monitoring mechanisms, and actively engaging employees in the process, organizations can navigate these challenges and foster a culture of continuous improvement and adaptability.

6. Documentation and Compliance:

Documentation Integrity and Learning Enhancement: The meticulous recording of deviations, including their root causes and corresponding corrective actions, plays a pivotal role in ensuring accountability and facilitating future reference. The comprehensive and accurate documentation of these aspects is crucial for fostering a robust learning process within an organization. Incomplete or inaccurate documentation has the potential to impede the learning curve, hindering the ability to derive valuable insights from past experiences.

Navigating Regulatory Compliance Challenges: The adherence to regulatory requirements in the management and documentation of deviations presents a multifaceted challenge for organizations. Meeting these regulatory standards necessitates a thorough understanding of the intricate frameworks governing various industries. Failure to comply with these regulations can have severe repercussions, ranging from legal ramifications to financial consequences. As such, organizations must invest in robust systems and processes to ensure that their deviation management practices align with the ever-evolving regulatory landscape.

Legal and Financial Implications of Non-Compliance: The failure to meet regulatory compliance standards in handling and documenting deviations can expose an organization to significant legal and financial risks. Legal consequences may include fines, penalties, or even legal actions, while financial implications can extend to reputational damage and a loss of stakeholder trust. Proactive measures to ensure compliance not only mitigate these risks but also contribute to the overall sustainability and resilience of the organization in the face of regulatory scrutiny.

Continuous Improvement Through Documentation: Beyond mere compliance, the meticulous documentation of deviations serves as a catalyst for continuous improvement. Analyzing past deviations and their resolutions provides valuable insights into organizational weaknesses and areas for enhancement. This iterative process fosters a culture of learning and adaptability, positioning the organization to proactively address challenges and optimize its operations over time.

In summary, the interplay of documentation integrity, regulatory compliance, and the associated legal and financial considerations underscores the critical role that robust deviation management practices play in organizational success. A proactive approach to documentation not only ensures compliance with regulatory standards but also serves as a cornerstone for continuous improvement, contributing to the overall resilience and adaptability of the organization in an ever-changing business environment.

7. Continuous Improvement:

Embracing a Culture of Continuous Improvement through Learning from Deviations:

Fostering a culture of continuous improvement is a fundamental necessity for organizations striving for excellence. The process begins with acknowledging that deviations from established norms are not merely setbacks but valuable opportunities for growth and refinement. The proactive approach of transforming deviations into learning experiences is pivotal for organizational development.

Challenges in Turning Deviations into Opportunities:
Despite the inherent importance of learning from deviations, many organizations grapple with the practical implementation of this philosophy. It is not uncommon for entities to face difficulties in seamlessly integrating deviations into their operations to derive meaningful insights. Overcoming this challenge requires a concerted effort to create an environment that not only tolerates deviations but actively encourages the extraction of valuable lessons from them.

The Role of Adaptability in Organizational Evolution:
Adaptability emerges as a cornerstone for organizational success in the face of deviations. The ability to evolve based on insights gleaned from past experiences is paramount. However, this adaptability is often hindered by various factors such as resistance to change and institutional inertia. Organizations must navigate these hurdles to effectively implement changes that lead to continuous improvement and innovation.

Navigating Resistance and Inertia:
Resistance to change and inertia are common adversaries that organizations encounter in their pursuit of adaptability. Overcoming these challenges necessitates a strategic and empathetic approach to change management. Addressing concerns, fostering a sense of ownership among stakeholders, and providing adequate support are crucial components in dismantling barriers to change.

Incorporating a Holistic Approach to Continuous Improvement:
A comprehensive strategy for continuous improvement involves not only learning from deviations but also proactively addressing the impediments to change. Organizations should cultivate a mindset that views deviations as opportunities for innovation and refinement. By fostering a collaborative and open culture, entities can create a resilient framework that embraces change and propels the organization towards sustained growth.

In conclusion, the journey towards continuous improvement requires a multifaceted approach. Organizations must not only recognize the importance of learning from deviations but also actively work towards creating an adaptive environment that can effectively translate these lessons into tangible enhancements. By overcoming resistance and inertia, and by incorporating a holistic approach to continuous improvement, organizations can thrive in an ever-evolving landscape.

8. Cultural Factors:

Culture of Accountability: When an organization fosters a culture of blame, it creates an environment where individuals may feel reluctant to report deviations or actively participate in root cause analysis due to the looming fear of facing negative consequences. This detrimental culture not only hinders transparency but also impedes the identification and resolution of issues that could potentially impact organizational success.

Nurturing a Feedback-Friendly Environment: Building a workplace culture that not only tolerates but actively encourages openness to feedback is a formidable yet indispensable task. Embracing deviations as invaluable opportunities for improvement, rather than as grounds for punishment, is essential for the sustained growth and prosperity of the organization. This mindset shift can foster a collaborative atmosphere where employees feel empowered to share insights and contribute to the continuous enhancement of processes.

Proactive Deviation Management: Effectively addressing these challenges demands a proactive and systematic approach to deviation management. This approach should prioritize continuous improvement as a central goal, emphasizing the need for robust systems that facilitate the reporting of deviations without fear of reprisals. Implementing clear communication channels and mechanisms for employees to express concerns and suggestions can further fortify an environment conducive to openness.

Commitment to Learning: A commitment to learning from experiences is a cornerstone of a healthy organizational culture. Instead of viewing deviations as failures, organizations should perceive them as valuable learning opportunities. Leaders should promote a growth mindset that encourages employees to analyze deviations, understand their root causes, and collaboratively implement solutions. By embracing a culture of continuous learning, organizations can adapt, evolve, and ultimately thrive in an ever-changing business landscape.

Emphasizing Communication: Effective communication is a linchpin in overcoming the challenges associated with blame culture and fostering openness to feedback. Leaders should prioritize transparent and timely communication, ensuring that employees are aware of the importance of their contributions in identifying and rectifying deviations. This not only builds trust but also reinforces the idea that addressing issues is a collective responsibility.

In conclusion, tackling a blame culture and cultivating openness to feedback necessitates a multifaceted and dedicated approach. By prioritizing continuous improvement, fostering a feedback-friendly environment, and instilling a commitment to learning, organizations can build resilience, adaptability, and a culture that thrives on collective efforts towards excellence.

 

How can we effectively handle a Deviation?

Effectively addressing deviations requires using a systematic approach that includes identification, in-depth analysis, strategic controls, and deep learning for deviations within a process or project. This requires a comprehensive approach that aims not only to address deviations but also gain valuable insights to improve overall performance. The ability to effectively address deviations contributes significantly to organizational resilience and continuous improvement.

To successfully master the complexities of deviation management, it is essential to introduce step-by-step instructions that serve as a guide for professionals and teams. This guide provides a structured framework for identifying deviations early, investigating root causes through careful analysis, implementing effective control measures to mitigate their impact, and most importantly, leveraging each deviation as a learning opportunity. do.

The first step involves a careful identification process that systematically pinpoints any deviations that may occur. Monitoring a process or project requires a keen eye for detail and a proactive approach. Once discrepancies are identified, the focus shifts to a comprehensive analysis that not only addresses the immediate problem, but also investigates the root cause. This analysis step is essential for developing a valid strategy to prevent similar deviations in the future.

Effective control systems are implemented to manage and mitigate the effects of identified deviations. Corrective actions are used that not only address the immediate consequences but also contribute to the overall improvement of the system. Control steps are essential to maintain operational stability and minimize disturbances due to deviations.

The final aspect of the guide emphasizes the importance of learning from deviations. Each example provides a unique opportunity to gain insight into weaknesses, inefficiencies, or unexpected problems in a process or project. Companies can leverage these learning opportunities to continually improve and optimize their operations. The iterative process of identifying, analyzing, monitoring and learning creates a cycle of improvement that strengthens resilience and adaptability.

In other words, an effective deviation management strategy goes beyond simple remediation and involves a holistic approach that includes proactive detection, in-depth analysis, strategic control, and continuous learning. By introducing step-by-step guidance, companies can flexibly address deviations and turn challenges into opportunities for growth and development.

1. Identify Deviations:

Define precise standards and expectations for both processes and projects to ensure a transparent framework. We encourage a culture of continuous improvement by continually evaluating and measuring performance against these established standards. We actively foster open communication channels to quickly identify and report deviations from established standards, supporting a proactive and collaborative approach to resolving issues and maintaining optimal project or process efficiency. These practices not only ensure accountability, but also create a dynamic environment where feedback is valued, leading to improved strategy and achievement of broader organizational goals.

2. Documentation:

Gather comprehensive information about the deviation by documenting intricate details, including its specific nature, broad scope, and potential impact. Record any deviations carefully and include relevant data, such as the date and time the deviation occurred. We also identify everyone involved in the deviation and create a comprehensive report that not only highlights the deviation but also provides a full understanding of the situation and potential impact. This careful documentation is critical to a complete analysis and allows for an informed assessment of the root cause of the deviation, its contributing factors, and its overall impact on the process or system involved. By collecting detailed records, companies can lay the foundation for informed decisions, corrective actions, and preventive actions to improve overall performance and compliance.

3. Root cause Analysis:

Conduct a comprehensive investigation of the underlying factors contributing to observed changes to gain a deeper understanding of the causes. Use analysis tools such as fishbone diagrams, five-cause diagrams, or failure mode and effects analysis (FMEA) to systematically identify and decipher the underlying issues causing deviations. This in-depth investigative approach is important not only for identifying surface symptoms, but also for exploring complex layers of causes.

Involve a multidisciplinary team of relevant stakeholders throughout the analysis process to ensure a holistic and diverse perspective. Including people with diverse skills and insights can increase the completeness and accuracy of your research. These joint efforts not only promote a more complete understanding of the disorder, but also the development of effective, targeted solutions.

Also consider integrating qualitative and quantitative data sources to strengthen your analysis. By combining empirical evidence, expert opinion, and historical data, you can create a more concise and accurate explanation of the root cause. This interdisciplinary approach contributes to a more resilient and adaptable research framework that can account for the complexities associated with identifying and resolving deviance.

Uncovering the complex web of factors contributing to change requires a multifaceted approach that leverages advanced analytical tools, engages multiple stakeholders, and integrates multiple data sources. This in-depth investigation lays the foundation for informed decision-making, strategic problem-solving, and implementation of preventive measures to prevent similar deviations in the future.

4. Impact Assessment:

Assess the impact of deviations on the overall workflow or project and carefully examine their impact and impact. Address the potential risks and consequences of deviating from the established path, considering both immediate and long-term impacts. Assess the broader impact on project planning, resource allocation, and stakeholder expectations to ensure a full understanding of how variations may disrupt the overall trajectory. It also analyzes the impact on interconnected processes and identifies dependencies that may be affected. By performing a thorough assessment, you can gain insight into many aspects of the transition and develop strategies to mitigate its impact, promoting a proactive and informed approach to project management.

5. Risk Mitigation:

Develop a comprehensive risk mitigation strategy in response to identified deviations. This involves developing a detailed plan that not only addresses the immediate problem, but also investigates root causes, implements corrective actions to fundamentally address these problems, and establishes preventative measures to prevent potential recurrence.

The first step involves an in-depth analysis of the risks associated with the deviation, identification of its causes, and assessment of its potential impact on the overall objectives. Once you have a clear understanding of these risks, you need to develop a structured plan that defines the specific actions you need to take to mitigate each risk. The plan should include both short-term measures to provide immediate relief and long-term strategies to ensure sustainable risk management over time.

It is important to implement corrective actions during this process. Addressing these causes of variation requires a targeted approach. It’s not just about solving an immediate problem, it’s about implementing systemic changes to prevent similar deviations from occurring in the future. This proactive attitude creates stronger and more resilient systems.

Additionally, it is important to consider both short-term and long-term strategies for a holistic approach to risk management. Short-term strategies may involve quick corrections and immediate responses to current deviations, while long-term strategies focus on sustainable solutions that protect the system from potential future risks. This dual approach allows organizations to effectively manage risk both immediately and over the long term.

The process involves a multifaceted approach that includes a combination of risk identification, detailed planning, corrective action, and short-term and long-term strategies. By adopting this comprehensive strategy, companies can not only mitigate the risks associated with deviations, but also strengthen systems that can successfully manage uncertainty.

6. Communicate:

Inform stakeholders of any deviations from established plans and explain the potential impact of such departures. Promote a culture of transparency by regularly informing all stakeholders of ongoing actions to address and mitigate the impact of deviations. Establish clear lines of communication for open exchange of information and ensure stakeholders fully understand the situation. This proactive approach to communication not only builds trust, but also ensures that everyone involved is well informed and promotes a collaborative environment where joint efforts can be focused on solving problems and achieving common goals.

7. Change Control:

When a deviation occurs, it is essential to carefully assess the situation and, if deemed necessary, improve and modify existing procedures or processes to smoothly implement the valuable lessons learned from the deviation experience. This proactive approach allows organizations to continuously develop and improve their operations based on real-world feedback.

Incorporating lessons learned from deviations into established procedures not only solves immediate problems, but also contributes to the larger process of organizational learning and continuous improvement. This adaptive mindset creates a culture of resilience and agility, allowing companies to effectively overcome unexpected challenges.

To maintain consistent standards and maintain compliance with quality standards, any changes or updates to procedures must be implemented through a formal change management process. This structured approach ensures that changes are thoroughly evaluated, documented, and approved prior to implementation. By establishing a formal change control process, organizations create a strong framework for managing change, mitigating risk, and maintaining a consistent and stable operating environment.

In other words, proactively updating processes to incorporate lessons learned from deviations, combined with a formal change control process, not only addresses immediate issues, but also promotes a culture of continuous improvement, adaptability, and quality assurance within the organization.

8. Continuous Improvement:

Create an organizational environment that grows through continuous improvement through careful review of deviations. Regularly participates in comprehensive process and project reviews to identify and analyze areas for improvement and optimization. Create a collaborative environment where you actively seek opinions and ideas from team members and value their unique perspectives and insights as valuable contributions to shared excellence. Develop a mindset that views change as a catalyst for growth and encourages continuous learning and adaptation. By building this culture of continuous improvement, companies can develop effectively, innovate, and remain resilient in the face of dynamic challenges.

9. Training and Awareness:

Conduct in-depth training for employees involved in specific processes to proactively mitigate similar deviations in the future. Increase employee awareness and understanding of the importance of following required procedures and policies. The purpose of this training plan is not only to correct past deviations but also to establish a culture of procedural discipline and integrity within the organizational structure. By increasing awareness of established protocols, employees can perform their roles accurately, reducing the likelihood of future deviations and promoting a culture of continuous improvement. The emphasis on training isn’t just limited to corrections. It represents a strategic investment in your organization’s operational efficiency and long-term compliance. When employees gain a deeper understanding of the rationale behind established procedures, they are more likely to internalize the importance of compliance, helping to create a work environment characterized by accountability, efficiency, and commitment to best practices. Additionally, these training plans can be designed to include interactive elements, case studies and real-world scenarios to increase engagement and put the knowledge gained into practice. Through regular refresher courses, feedback mechanisms and continuous reinforcement through performance evaluations, we will promote a resilient organizational culture that integrates best practices into daily operations, prioritizes procedural integrity and minimizes the risk of future deviations.

10. Document Corrective Actions:

Carefully record and document corrective actions taken to address identified deviations within the operating framework. Maintains complete records of changes to existing processes, policies or procedures in direct response to identified discrepancies. This document is a collection of important insights into the evolving organizational landscape and demonstrates the adaptability and resilience of existing systems. By carefully recording the corrective actions taken, an organization not only ensures transparency and accountability, but also creates a valuable resource for continuous improvement and future decision-making. These documented changes provide a holistic view of the dynamics of an organization’s response to deviations, fostering a culture of learning and agility. This systematic approach allows organizations to not only solve immediate problems, but also build a solid foundation for sustainable excellence and adaptability in the face of increasing challenges.

11. Performance Monitoring:

Continuous monitoring of the performance of modified processes is essential to ensure sustainable improvement. Establish a strong feedback mechanism to quickly identify and resolve any potential problems that may arise during implementation of revised processes.

It is important to emphasize that deviation management is not a one-time task, but a continuous and dynamic process. To prevent future recurrences, it is important to maintain a relentless commitment to continuous improvement and be proactive in identifying and mitigating potential deviations. Build a culture of adaptability and improvement by regularly evaluating performance indicators and collecting feedback from a variety of sources. By adopting a proactive, continuous improvement mindset, companies can foster resilience and improve the overall efficiency and reliability of their processes.

What happen when a Deviation is not properly investigated?

When a deviation is not properly investigated, several negative consequences can arise, depending on the context. Deviations refer to variations or departures from established processes, procedures, or standards. Failing to investigate deviations thoroughly can lead to the following issues:

1. Quality and compliance issues:

If variations within the manufacturing process are not addressed, product quality integrity can be compromised. Failure to correct these deviations can lead to a number of negative consequences, including potential defects, reduced product quality, and safety hazards. Moreover, when compliance is compromised, the impact extends beyond the product. Many industries have strict regulations that require any deviations from established manufacturing standards to be carefully inspected and documented.

When a manufacturing process deviates from prescribed standards, a variety of problems can arise that can seriously impact the final product. Quality control errors can result in defective components being installed, which can lead to defective items that not only erode consumer trust but also pose potential safety hazards. The presence of defective products not only damages the manufacturer’s reputation, but can also lead to legal consequences.

Additionally, in sectors where strict guidelines apply, compliance with the regulatory framework is essential. Not only does non-compliance expose companies to legal risk, but it also puts safety and public trust at risk as production deviations go unchecked. Regulatory authorities often require thorough investigation and detailed documentation to ensure that manufacturing processes meet established standards.

Preventive and corrective actions taken in response to production deviations play a critical role in maintaining overall product quality, maintaining regulatory compliance, and protecting consumer welfare and the reputation of the industry as a whole.

2. Repetition of errors:

Without thorough investigation, the underlying factors causing churn cannot be identified. Failure to identify this root cause greatly increases the likelihood that the same mistake will occur again in the future. This perpetuates a problem cycle in which unresolved problems resurface over and over again, creating ongoing problems and preventing sustainable solutions from being achieved. Thorough investigation is essential not only to resolve immediate problems, but also to break the vicious cycle of repeated failures and build more resilient and stable systems over the long term. By investigating the root causes of deviations, companies can take preventative action, strengthen processes, and take proactive action.

3. Risk of security incidents:

Deviations from established security protocols in industries such as healthcare, pharmaceuticals, and manufacturing can pose serious risks to the well-being of employees, consumers, and the general public. If these deviations are not thoroughly reviewed, they can go beyond simple procedural errors and lead to potentially serious safety incidents or incidents that threaten the operational integrity of these critical sectors.

In the healthcare sector, where patient well-being is fundamental, compliance with safety protocols is not only a regulatory requirement, but also a fundamental aspect of ensuring quality care. Deviations from established procedures can lead to uncertainty in the treatment process and potentially put the patient’s health and safety at risk. It is therefore important to carefully investigate any deviations from safety standards to maintain the trust and well-being of both healthcare professionals and patients.

In the pharmaceutical industry, where accuracy and precision are critical, deviations from safety guidelines can affect the quality and effectiveness of the drug product. If these discrepancies are not promptly addressed and investigated, substandard medicines may be distributed, posing a threat to public health and undermining trust in the industry. Rigorously reviewing any deviations from safety protocols is critical to maintaining the integrity of the pharmaceutical supply chain and protecting the health of end users.

Even in the manufacturing industry, where product production is a complex and complicated process, deviations from safety standards can lead to operational inefficiencies, product defects, and in extreme cases, major accidents. Failure to thoroughly investigate these deviations not only exposes workers to unnecessary risk, but also endangers the end users of the manufactured products. Strict safety protocols and careful investigation of any deviations are essential to maintaining the overall reliability and reputation of a manufacturing operation.

Strict adherence to safety protocols in this inherently important sector is not a mere bureaucratic formality. This is an important part of protecting the well-being of individuals, ensuring product quality, and maintaining the integrity of the industry as a whole. Close investigation of violations plays a critical role in preventing safety incidents, promoting continuous improvement, and creating a culture of responsibility and accountability in the healthcare, pharmaceutical, and manufacturing industries.

4. Financial Consequences:

Inefficient or faulty operating processes can result in serious financial disaster for a company. A good example of this is when deviations in the manufacturing process go unnoticed. These oversights can result in a variety of negative consequences, including product defects and product recalls, legal penalties, and serious damage to the company’s reputation in the marketplace.
Digging deeper into the complexity of the problem, the financial losses caused by inefficient processes go beyond the immediate cost of correcting the errors. For example, product recalls require significant financial resources to recover, replace, and dispose of defective items. Additionally, the legal consequences of these deficiencies could result in prolonged litigation, resulting in significant fines, settlements and legal fees, which could further weaken the Company’s financial stability.

The damage is not limited to financial impacts. It also has a domino effect on the company’s reputation. Consumers who hear or learn about a defective product may lose trust in the brand, resulting in loss of customer loyalty and market share. Negative publicity from recalls and lawsuits can tarnish a company’s image and make it difficult to regain the trust of existing and potential customers.

This means that troubleshooting problems and fixing inefficient or flawed processes is not only a matter of preventing immediate financial loss, but is also critical to ensuring your company’s long-term financial health, reputation, and profitability in a competitive marketplace. This highlights the importance of strong quality management systems and proactive management strategies to reduce risk and ensure sustainable success.

5. Loss of customer trust:

When a product or service deviates from established quality standards during manufacturing or distribution, the impact goes beyond immediate concerns. In these cases, loss of customer trust becomes a critical issue with far-reaching consequences. This loss of trust can cause lasting damage to a company’s brand reputation and threaten customer loyalty, negatively impacting the company’s overall success and sustainability.

Product or service quality is the foundation for fostering a positive customer experience. When inconsistencies arise and these fundamental aspects are compromised, customers may perceive the brand as unreliable or unable to maintain promised standards. These negative perceptions can lead to a trickle-down effect where customers are not only dissatisfied with a particular transaction, but also question the company’s overall integrity and commitment.

When customer trust declines, it can have a domino effect that affects purchasing decisions and brand promotion. In an age when consumers have so many choices, loss of trust in a company’s ability to deliver consistent quality can lead consumers to look for alternatives. Reputational damage can extend beyond your immediate customer base as negative word of mouth spreads and impacts potential customers who may dissuade them from engaging with your brand.

Moreover, the long-term consequences of declining customer trust extend beyond the immediate financial impact. Building and maintaining a positive brand image is an ongoing process that requires time, resources, and a strong commitment to quality. When trust is damaged, the process of rebuilding and regaining customer trust can be difficult and requires significant investments in marketing, communications and quality improvement initiatives.

In essence, the impact of deviations from quality standards extends beyond the immediate realm of product or service nonconformity. This has far-reaching implications for the fundamental structure of a company’s relationship with its customers, influencing its perception, behavior and ultimately its sustainability in a competitive marketplace. Therefore, an ongoing commitment to maintaining quality standards becomes not only a business imperative, but also a strategic imperative that ensures the company’s continued success.

6. Ineffective problem solving:

Without a thorough and complete investigation, an organization may not fully understand the root causes of deviations from established processes or standards. This lack of understanding is a serious barrier to formulating and implementing corrective and preventive actions. A thorough investigation is essential to address the complexity of irregularities as it reveals multiple aspects that contribute to deviations.

By performing a thorough audit, organizations gain valuable insight into the complex factors that lead to deviations. This in-depth understanding is the basis for developing targeted and effective corrective actions. Without this deep understanding, organizations risk adopting superficial solutions that only address the symptoms and not the root cause.

Additionally, a thorough investigation not only uncovers the immediate causes of deviations, but also addresses institutional issues and procedural deficiencies. This holistic approach ensures that advanced corrective actions are not only reactive but also preventative in nature, protecting your organization from recurring problems in the future.

In-depth research also provides learning opportunities for organizations and promotes a culture of continuous improvement. This allows you to identify potential vulnerabilities in existing processes and systems, allowing you to take proactive steps to improve overall operational resilience. If you don’t invest time and resources in comprehensive research, you may miss out on opportunities for organizational learning and improvement.
In summary, the absence of a proper investigation jeopardizes the organization’s ability to comprehend the intricate web of factors contributing to deviations. This lack of insight undermines the development of effective corrective and preventive actions, leaving the organization susceptible to the recurrence of similar issues. A thorough investigation not only addresses immediate concerns but also serves as a catalyst for organizational learning and improvement, reinforcing the organization’s capacity to navigate future challenges with resilience and foresight.

7. Audit and inspection results:

As part of their important duties, regulatory agencies carry out thorough audits and inspections to ensure compliance with established standards and regulations in various sectors. The main purpose of these audits is to ensure compliance with the various rules and guidelines applicable to a particular sector. Failure to thoroughly investigate and address deviations from these standards can expose your organization to significant risk.

If regulators find discrepancies in an audit, there are potential consequences that could have far-reaching consequences. Non-compliance may result in fines, penalties or other regulatory actions. These sanctions serve not only as a deterrent, but also as a mechanism to strengthen and maintain the integrity of the regulatory framework.

Moreover, failure to promptly address identified issues can damage the reputation and credibility of the organization being investigated. In addition to financial penalties, more serious consequences may include: B. Closure of activity, revocation of license or legal action. Collateral damage goes beyond the immediate financial impact and impacts the overall performance and sustainability of the organizations involved.

It is important for businesses and organizations to take a proactive approach to regulatory compliance and conduct rigorous internal reviews and investigations to identify and address potential non-compliance before regulators take action. This not only reduces the risk of disciplinary action, but also establishes a culture of care and accountability within the organizational structure.

In essence, government audit and inspection processes serve as an important mechanism to maintain the integrity of the industry and ensure that companies operate within established legal and ethical boundaries. By understanding and proactively addressing deviations, companies can navigate a complex regulatory environment, protect their operations, and contribute to the overall stability and reliability of the industries in which they operate..

8. Operational Inefficiencies:

Operational inefficiencies can arise due to unresolved deviations and can lead to a cascade of problems arising from the root cause of the problem. These unresolved inconsistencies can have a serious impact on many aspects of an organization’s performance, including productivity, resource utilization, and overall business performance.

To effectively address these risks, companies must establish and maintain a strong deviation management system. These systems include comprehensive investigation processes, careful documentation practices, and implementation of corrective and preventive actions. By carefully following these protocols, companies can not only solve immediate problems, but also create a path for continuous improvement.

An in-depth investigation process helps identify the root cause of the anomaly and provides insight beyond the symptoms above. This deep understanding allows for targeted, effective corrective action that not only resolves the immediate problem, but also helps prevent similar incidents in the future.

Documentation plays a key role here as it serves as detailed documentation of deviations, investigations and actions taken. A well-maintained documentation system not only contributes to accountability, but also provides a valuable resource for future reference, allowing companies to learn from past experiences and continually improve their processes.

The basis of a proactive approach to deviation management is the implementation of corrective and preventive actions. Corrective actions address existing problems, while preventive actions aim to eliminate potential problems. This dual strategy not only addresses immediate challenges, but also strengthens the company against future obstacles and promotes a culture of continuous improvement.

By emphasizing variation management, companies not only protect their day-to-day operations, but also maintain critical aspects such as quality and compliance. This commitment to maintaining high standards contributes to the overall effectiveness of the organization and strengthens the company’s resilience and adaptability in an ever-changing environment.

This means that a proactive, comprehensive approach to variance management is essential for companies looking to improve operational efficiency, maintain quality standards, and improve overall business performance. Implementing a strong deviation management system promotes a culture of continuous improvement and empowers your organization to overcome challenges and succeed in a dynamic business environment.

Example of Deviation

Several instances of deviations have been observed in drug or device firms, highlighting potential challenges and risks in their operations. These deviations encompass a spectrum of issues, and it is crucial to address them effectively to ensure the safety, efficacy, and quality of pharmaceutical products. Here are several common examples that underscore the diverse nature of these deviations:

1. Unanticipated Delays:

Unforeseen delays in manufacturing or testing processes pose a considerable risk, potentially leading to product degradation or expiration. Identifying and mitigating the causes of these delays require a proactive approach, emphasizing effective project management, supply chain resilience, and contingency planning to maintain product quality and meet regulatory timelines.

2. Environmental Deviations:
Deviations in environmental conditions, such as fluctuations in temperature, humidity, or air quality, can exert a profound impact on product stability and sterility. It is imperative for firms to implement stringent environmental monitoring programs to detect and address deviations promptly, thereby ensuring the integrity of the manufacturing environment.

3. Equipment Failures and Malfunctions:

One prevalent deviation involves equipment failures or malfunctions, which have the potential to introduce contamination or yield inaccurate test results. These technical glitches can compromise the reliability and precision of manufacturing processes, necessitating a rigorous approach to equipment maintenance and monitoring.

4. Human Errors:

Human errors represent another significant category of deviations, encompassing miscalculations, mislabeling, or the failure to adhere to approved procedures. These mistakes can occur at various stages of the production and testing processes, underscoring the importance of continuous training, process validation, and robust quality management systems.

5. Raw Material and Supply Chain Issues:

Deviations related to raw materials or supply chain disruptions can result in variations in product composition or quality. Establishing robust supplier quality management programs, conducting thorough risk assessments, and implementing contingency measures are essential strategies for mitigating these deviations and maintaining the consistency and reliability of pharmaceutical products.

By recognizing and comprehensively addressing these diverse deviations, drug and device firms can enhance their overall quality management systems, uphold regulatory compliance, and ultimately ensure the delivery of safe and effective products to consumers. This approach fosters a culture of continuous improvement and risk mitigation, aligning with the industry’s commitment to patient safety and product excellence.

 

 

 

Annexure:

Annexure-I: Deviation Form
Annexure-II: Deviation Register
Annexure-III: Investigation Template
Annexure-IV: Investigation Register

Deviation Procedure Read More »

Change Control Procedure

Change Control, Purpose:

Change Control, The purpose of this SOP is to define the requirements that all planned changes which have potential to impact the quality of the product are controlled through a systematic, standard and effective approach. This approach of controlling change will ensure:
[][]Safeguard of quality (Safety and efficacy of the product)
[][]Ensure compliance with legal and regulatory requirements
[][]Traceability of changes made through the lifecycle of a product or facility
[][]Assessment and management of all risks (Quality, Business and EHS) associated with the implementation of changes.

Change Control, Scope:

Applies to all planned changes (including emergency/temporary/permanent changes) that have the potential to affect GMP, Product Quality, Safety, Efficacy, Stability, EHS and the Validation status of Processes, Facilities and Systems of General Block and Sterile Block at XX Pharmaceuticals Ltd.
[][]Few examples of planned changes within the scope of this SOP are:

Production

GMP Documents :
Validation protocol.

Processes :

[][]Manufacturing or Packaging processes
[][]Process (time, mixing speed, temperature, order of addition etc).
[][]Removal/replacement/addition of API or excipients (Formula amounts, overage)
[][]Batch size, production scale
[][]In process controls
[][]Cleaning methods or processes.
[][]Coating weight of tablets, weight of capsule shell, fill weights or volumes.
[][]Any trial (machine/process) work.
[][]Shelf life, expiry (including hold times at intermediate production stages).

Manufacturing Facilities & Equipment :

[][]Equipment, critical device.
[][]Manufacturing/packaging suite/ location.
[][]Introduction of new product/ machinery.
[][]Change of critical spare parts of machineries.
[][]Product & materials
[][]Shape or dimension of product.
[][]Imprints/embossing or other markings on product.
[][]Colour of the product
[][]Packaging Components
[][]Intermediate/Primary/Secondary packs
[][]Product contact components
[][]Disinfectants / Detergents
[][]Product Contact Lubricants

Quality Assurance

Control Documents :

[][]Specification (product, API, excipients, packaging) and Control Direction
[][]Stability protocol.
[][]Artworks.
[][]Qualification protocol
[][]Technical agreements with third party or any service provider.
[][]Colour shades.
[][]Approved supplier list

Methods & procedure :

[][]Sampling or Testing processes
[][]Test parameters (time, run time, temperature, solvent etc).
[][]Removal/replacement/addition of tests.

[][]Environmental monitoring system.
[][]Microbiological monitoring location, frequency and limits

Facilities & Equipment :

[][]Laboratory equipment.
[][]Critical spare parts of equipment.
[][]Introduction of new equipment.

Supplier :

[][]Supplier of API, excipients or packaging components
[][]Change in supplier, manufacturing location, material, pack size or mode of packaging.

Engineering Services

GMP Documents :

[][]Qualification protocol
[][]Drawing & facility layout
[][]Master Calibration list

Facilities & Equipment :

[][]New/additional location for assembly, manufacturing, packaging and testing.
[][]Building Management e.g. Building Management system, pest control.
[][]Calibration frequency or limits/tolerance.
[][]Utilities such as facilities cleaning, compressed air, vacuum, electricity and water.
[][]Building / structural work (e.g. new facility, or installation of utility equipment).
[][]Any change in equipment design
[][]Substitution of any engineering parts.

Services /Utilities :

[][]Water Generation and Distribution
[][]Steam Generation and Distribution
[][]HVAC, vacuum and compressed air modification

Others

[][]Any change relating to a product manufactured at third party
[][]Change relating to product/technology transfer.
[][]Any activity that have the potential to affect EHS
[][]Format change of any controlled documents such as Batch Manufacturing Record, Batch Packaging Record & Control Direction

The process does not apply to the following as these are managed separately by individual SOPs:

[][]Any unplanned incident/changes
[][]Engineering replacement with identical/equivalent parts (procured from the approved sources having the same functionality , specification and serial number)
[][]Routine servicing or preventive maintenance.
[][]Changes during Product Development/trial
[][]Routine revision of any controlled documents (e.g. SOP, BMR, Test methods etc)
[][]SOP/BMR/BPR change to comply with any requirements where the reason and history of changes are mentioned in the revision details.
[][]Like for Like Change

Definitions / Abbreviation:

[][]Change Control Procedure: A formal controlled documented process by which qualified representatives from appropriate discipline, review, propose and make changes to an approved system.
[][]Temporary change: A change (departure from any established procedure/system/process) initiated for the evaluation of proposed procedure/system/process, which has been taken with prior approval to achieve the desired output, allowed for one time change and limited to a particular batch or campaign batches. For example change in manufacturing equipment.
[][]Permanent change: A change initiated based upon scientific rational or historical cGMP data or data generated through temporary changes.

[][]Minor Change: A change unlikely to have a detectable impact on the critical attributes of a system, process, material, product or procedure. (For example: equivalent rewording of instructions or batch record format changes
[][]Major Change: A change that could have a significant impact on the critical quality attributes of a system, process, material, product or procedure. (For example: packaging design change, order of addition of components, mixing parameters in a process).
[][]Critical Change: A change that would be likely to have a significant impact on the critical attributes of a system, process, materials, product or procedure. (For example: a change in critical equipment or change in manufacturing site.)

[][]Planned Change: A change that is planned and given the associated lead time.
[][]Unplanned Change: An unplanned change is a change that occurs unexpectedly on an individual batch or process and is documented via the deviation system.
[][]Engineering replacement with identical parts: Parts that meet the following criteria are known as identical parts and replacement for these Change Control is not required:
=>Same functionality.
=>Same specification.
=>Same manufacturer.
=>Same part number.
[][]Engineering replacement with equivalent parts: Parts that meet the following criteria are known as equivalent parts and replacement for these Change Control is not required:
=>Same functionality.
=>Same specification.
=>Could be a different manufacturer.
=>Could be a different part number from the same manufacturer.

Responsibilities:

[][]The roles and responsibility is as follows:

Concern Department (change initiator)

[][]To propose the change.
[][]Assess if the change is within scope of the change control process.
[][]Provide sufficient supporting information necessary for initial assessment of the change.
[][]To intimate Quality Compliance for issuance of the change control form.
[][]To make necessary entries in the change control form.
[][]To take approval of Department Head and send the form to Quality Compliance for review.
[][]To take approval from Manager, Quality Assurance
[][]To take execution approval from Manager, Quality Assurance prior to execute the change.
[][]To generate relevant supporting data in consultation with related department for compliance of the recommendation provided in reference to change implemented.

Quality Assurance Personnel

[][]To make necessary entries in the change control register.
[][]To issue change control form after assigning change control number and making necessary entries.
[][]To review the change control form and provide the recommendations as impact analysis against the change initiated.
[][]To review actionable mentioned in the impact analysis that are required to be in place prior to implement proposed change and to provide execution approval.
[][]To send the change control for approval to Manager, Quality Assurance in case of impact on regulatory aspects and to obtain approval.
[][]To intimate third party for changes related to their products.
[][]To intimate the changes related to customer, in accordance with the provision as defined in the quality agreement.
[][]To generate and issue corrective action and preventive action (CAPA) form if required for recommendations provided to complete the activity in concern to change implemented.
[][]To review and evaluate the data / assessment report generated during study in consultation with Manager, Quality Assurance.
[][]To close the change control after ensuring implementation and to make necessary entries in change control register.
[][]To retain all change controls in Quality Assurance department.
[][]To circulate a list of change controls which are in issued status for follow up and progress review. The list shall be circulated on monthly basis

Concern Department Head

[][]To review and evaluate filled change control form and give approval.
[][]To recommend possible impact in change control form.
[][]To send the filled change control form for review to Quality Compliance.
[][]To revise the document in consultation with all respective department.
[][]To arrange and ensure generation of the supporting data/ assessment report to comply the recommendations.
[][]To take execution approval from Manager, Quality Assurance prior to execution of the changes.

Manager, Quality Assurance

[][]To provide recommendations / review the adequacy of impact analysis for recommendation provided in respect to change initiated.
[][]To decide change review level of changes proposed.
[][]To approve the change control.
[][]Ensure all relevant changes are managed according to SOP.
[][]Trending of change controls.
[][]Assess, review and approve a proposed change for implementation

Procedure:

Checking of scope for Planned Change:

[][]Before initiating the process the initiator will check if the planned change is within the scope defined in this SOP. If there is any doubt about the scope of change then the initiator will discuss with Quality Assurance Department.
[][]Before initiating the proposal the initiator will check whether any change proposal on the similar subject (Product/equipment/process/materials) still remains open that need to be implemented.

Procedure for Change Initiation :

[][]Upon identification of need of change(s), concern person shall ask Quality Assurance personnel to issue “Change Control Form” (Refer Annexure-I).
[][]Quality Assurance personnel shall make following entries in “Change Control Form” while issuance and similar entries in “Change Control Register” (Refer Annexure-II).
[][]Change Control No. :
[][]Change control No. shall be assigned as per below explained numbering system.
[][]Change control number shall be changed every year.

[][]Change control number shall be alphanumeric system containing 11 characters. Numbering breakdown is as follows: CCyy/Area code/xxx.
Area Code is as follows:
=>General Issues GI, Common issues that affects more than one area.
=>General Block : GB
=>Sterile Block : SB
=>For example: CCXX/GB/001.

[][]The first two alphabets shall stand for Change control
[][]Next two numeric characters shall stand for year code XX shall denote year 20XX.
[][]Next character is slash (/), followed by two capital letter stands for area code of General Block at XX Pharmaceuticals Ltd.
[][]Next character is slash (/), followed by three numerical shall stand for serial number, which shall start every year from 001. For example first change control no CCXX/GB/001 and second CCXX/GB/002, third CCXX/GB/003 ….. for any change.
[][]In case of Sterile block, Change control number shall be SC13/CB/001 and so on. Two capital letter CB stands for area code of Sterile block at XX Pharmaceuticals Ltd.

[][]The number will be unique; if proposal is withdrawn/ rejected the same number will never be used again.
[][]Initiator: Name of the person to whom the change control is issued shall be written.
[][]Originating Department: The name of the department to whom the change control is issued shall be written.
[][]Issued By: The Quality Assurance Personnel who is issuing the change control shall put his/her initial with signature.
[][]Date of Issuance: Date on which the change control is issued shall be written.
[][]Product / Material / Document Name / SOP Title: Name of product/ material/ document title whatever applicable shall be mentioned for which the change is initiated and rest shall be stricken out.

[][]Batch no. /Lab control no. / Document No. : In case of temporary change, batch number of the product or Lab control No. of material for which the change is initiated shall be written.
In case of permanent change, document number (Master BMR No., SOP No., Specification No. etc. with version number) for which change is initiated shall be written.
[][]Type of Product (Country): Whether product is for domestic market or export market shall be mentioned. Specify the name of country as applicable, If the change is related to export product, name of region or country for which the product is being manufactured shall be mentioned.

[][]Change Type: Put the tick mark on appropriate change type.
[][]Concern person shall further fill the change control form as explained under below. In case space provided in change control form is not sufficient to accommodate the changes, below details shall be given on separate sheet in following type of table. This attachment shall be prepared and checked by concern department and reviewed by Quality Assurance.

Sl. No.Existing SystemProposed ChangeReason/ Justification Impact analysisChange review level
Prepared by/date
(Change Initiator )
Checked by/date:
(Department Head)
Reviewed by/date:
(Manager, Quality assurance)

[][]Existing System: Write details of existing process / formula / procedure / equipment or specification that is being followed.
[][]Description of Proposed Change: Write details of proposed process / formula / procedure / equipment or specification that is to be followed.
[][]Reason/Justification/Benefits for proposed change :In case of Direct Change, write the clear reason (wherever possible) for change initiated along with justification based on supporting data like history, trend, stability data, scientific rationale, event / audit observations and experience or any other to ensure no adverse impact on product quality.
[][]Temporary changes: Confirm that a search for similar changes been performed. Put the tick mark on appropriate box and write the date of expiry for temporary change.
Evaluation for Requirement of Change: If not justifiable
[][]The filled change control shall be reviewed by Concern Department Head and Manager, Quality Assurance or Designee. If the requirement for change is not justifiable or not agreed, either to Concern Department Head or Manager, Quality Assurance or Designee, they shall include justification to close the change control.
[][]The change control form and register shall be updated for closure by Quality Assurance personnel and change control form shall be retained in Quality Assurance department.
[][]Evaluation for Requirement of Change: If justifiable.
[][]Upon evaluation, if the requirement for change is justifiable or agreed, Concern Department Head and Quality Assurance personnel, they shall further allow carrying forward change control by signing it, for approval of GM, Plant and Manager, Quality Assurance.

Recommendations for Impact Analysis :

[][]Concern Department Head and Manager, Quality Assurance or his Designee shall provide recommendations for impact analysis to support ultimate output.
[][]The respective impacted Department Head shall be informed for the recommendations provided under each impact and approval for the same shall be taken from the impacted Department Head.
[][]Change control shall be informed to customer, in accordance with the provision as defined in the quality agreement.
[][]Based on feedback obtained further course of change control implementation shall be decided.
[][]If change control is not approved by third party or not acceptable to third party as per quality agreement, then change control shall be closed with the justification that particulate batch cannot be dispatched to respective third party but it can be sent to different third party if it fulfills requirements of different third party.
[][]If that particular drug product has to be dispatched to the third party with current formula then different product Item Code shall be given.
[][]While batch release Quality Assurance shall ensure that product requirement is fulfilled as per quality agreement during dispatch to different third party.
[][]Adequacy of impact analysis through recommendation shall be approved by Manager, Quality Assurance or Designee.
[][]For new system introduction change control shall be raised upon finalization of draft SOP.

Approval :

[][]All change controls shall be approved by Manager, Quality Assurance.
[][]Upon ensuring all approval, the originating department shall initiate preparatory work as recommendation provided to execute the changes proposed.
[][]The Quality Assurance Executive or his Designee shall review / verify all required actionable mentioned in the impact analysis(possible impact) that are required to be in place before implementation of proposed changes and provide execution approval by signing the change control.
[][]Originating department shall start to execute or implement the change only after getting approval for execution from Quality Compliance. The approved change control shall be provided to change initiator for execution of changes.

CAPA (Corrective Action and Preventive Action) Issuance and Monitoring :

[][]Quality Assurance shall issue CAPA form for long term corrective action and preventive action(s) to the concern impacted Department Head to monitor the recommendation as applicable.
[][]The CAPA shall be issued based on discretion of Manger, Quality Assurance.

Execution :

[][]Details of changes shall be explained by Quality Assurance personnel to concern persons either through mail or by conducting training as recommended in impact analysis / by sending scanned copy of change control form through mail.
[][]The concern person shall execute the change in coordination with Quality Assurance & shall prepare assessment report / data.

Review of Recommendations :

[][]After execution of the change the Concern Department Head and the impacted Department Head shall submit the CAPA form along with respective supporting data / assessment report if applicable to Quality Assurance for review of recommendations.

Impact Evaluation and Conclusion :

[][]Based on review of data / assessment report / outcome / results (satisfactory / not satisfactory) Quality Assurance shall make final conclusion, whether the change was executed successfully or not and shall close the same.

Time Line for Closure of Change Control Form :

[][]After the change is implemented, then the CC form shall be closed by Quality Assurance personnel, within 30 calendar days.
[][]Quality Assurance shall track the open change controls while issuing new change control to initiating department.
[][]New change control shall not be issued if for a same system/equipment/material/product/document and same stage about 3 change controls are already open.

Updating of Change Control Register :

[][]After closing the Change Control Quality Assurance shall update the Change Control register.
[][]All the Change Controls – Permanent / Temporary shall be retained in Quality Assurance Department.
[][]Note: In case of a change initiated for one document which may impact other document(s), the respective document(s) can be revised with reference to the same change control initiated for mother change. The document dedicated change control number system shall not applicable in this case.
[][]In addition to mother changes other changes if required can be clubbed and a separate attachment can be attached to mother change control and all persons who have involved in approval of mother change control shall sign the addendum of mother change control.

Batch release of Change Control impacted batch:

[][]Change Control impacted batch will not be released until formal closing.
[][]Any validation/trial batches produced as supporting evidence for the change proposal will be quarantined until formal closing of Change Control proposals.
[][]In some circumstances, to allow batch release, Manager, Quality Assurance may approve concurrent release of the impacted batches through a risk assessment by the owner.

Annexure:

Annexure-I: Change Control Form
Annexure-II: Change Control Register

Change Control Procedure Read More »

SOP for SOP Preparation and Handling Procedure

SOP for SOP, Purpose :

SOP for SOP, The purpose of this SOP is to define the stages, responsibilities and structure for the creation, distribution, handling, controlling, revision & retrieval of all operating procedures of XX Pharmaceuticals Ltd.

SOP for SOP, Scope :

This SOP applies to all functions in order to prepare, review, control and authorize/approve any procedure.

Definitions / Abbreviation:

[][]Standard Operating Procedure (SOP): A written authorized procedure, which gives instructions for performing operations.

Responsibilities:

[][]The roles and responsibility is as follows:

Author(Who prepares the SOP)

[][]Ensure that the document is technically correct and reflects the required working practices.
[][]Initiate the preparation of SOP through the inputs from the employees directly concerned with the activity.
[][]Responsible for circulation of SOP for comment and resolution of any differences of opinion.

Technical Expert

(Any person who has basic understanding on the subject matter)
[][]Review the SOP and formally notify their agreement to SOP owner within a stipulated time.

Functional Head

[][]To confirm the content, accuracy and detailing about of SOP.
[][]Verify the SOP against XX Pharmaceuticals Ltd. master documents and current regulatory requirements and approve it.

Quality Assurance Executive

[][]To maintain the original copy of the SOP.
[][]To issue controlled copy of the SOP and maintain issuance record.
[][]To retrieve the controlled copy of the SOP when it is superseded.
[][]To destroy the SOP as per procedure.
[][]To control and monitor the review process of the SOP.

Manager, Quality Assurance

[][]Approve all SOPs that have direct/indirect impact on product quality.

Procedure:

[][]Note: It will be applicable for any SOP of general precautions or operational safety.
[][]The process for developing and managing any SOP includes picking of right format, number generation, drafting, review, approval, issuance, distribution, periodic review, revising, withdrawing, archiving and destruction.

[][]Layout Designing for SOP: Before preparation of a SOP, following preliminary requirements are to be meet:

Format of SOP

[][]Standard Format (Annexure-I) shall be used for preparing any Standard Operating Procedure.
[][]The format of this SOP should be used to maintain the same text fonts, page borders, and general document format as explained here.

ParticularsFont sizeFont Font Style
In Header: Company LogoN/AN/APosition is ‘Left side’
In Header: Company Name14ArialBold, All Letters in Capital, Position is ‘Centered’ (both in Horizontally & Vertically)
In Header: Plant Address08ArialAll words are Regular but “Plant” is in bold. Position is ‘Centered’ (both in Horizontally & Vertically)
SOP Title10ArialBold & Uppercase
Heading10ArialBold
Text10ArialRegular
In footer10ArialBold, Position is ‘Left (indent)’ in Horizontally & ‘Centered’ in Vertically

Page Set Up

Margin:

[][]Top : 0.75

[][]Bottom : 0.75

[][]Right : 0.75

[][]Left : 0.75

[][]Gutter : 0.00

[][]Header : 0.5

[][]Footer : 0.5

Note: All Measurements at Inch.

[][]Paper size: A4 size, offset paper

[][]Orientation: Portrait (However landscape orientation may be used for annexure or if required).

[][]Header: Same for all pages [Annexure-I]

[][]Footer: Same for all pages except first. In first page there is no footer. [Annexure-I].

[][]Heading of the main content should use appropriate heading number such as 1, 2, 3 etc.
[][]Subheading may be included in any of the content sections using appropriate heading numbering such as 1.1, 1.2 etc.
[][]Further subheading may be included in any of the sub content sections using appropriate heading numbering such as 1.1.1, 1.1.2 etc.
[][]Header & Footer: Each page header must contain the following information:
[][]Title: Mention title of the SOP, which is expressive of the subject of the SOP.
[][]SOP Number: All the SOP numbers must be unique, unambiguous and unanimous. Referencing should be done in such a manner that it reflects either the function or purpose of this SOP. Standard format of SOP number is as – ‘SOP /Sectional Ref/Sequential SOP No. / Version No.’
[][]Sectional Reference is the predefined department/Section code to identify the SOP controlling department.

The following ‘Sectional Ref’ numbers must be used at the time of preparation of SOPs.

[][]Production (General):  PRO
[][]Production (Sterile): S-PRO
[][]Packaging (General): PKG
[][]Packaging (Sterile): S-PKG
[][]Warehouse (General): WH
[][]Warehouse (Sterile): S-WH
[][]Quality Assurance (General): QA
[][]Quality Assurance(Sterile): S-QA
[][]Quality Control(General): QC
[][]Quality Control(Sterile): S-QC
[][]Microbiology(General): MIC
[][]Microbiology(Sterile): S-MIC
[][]Product Development(General): PD
[][]Product Development(Sterile): S-PD
[][]Engineering: ENG
[][]HR & Admin: HR
[][]Supply Chain: SC
[][]Information Technology: IT
[][]Environment, Health &safety: EHS

A three digit Sequential number shall be assigned to the SOP. This number cannot be reassigned to any other SOP even after deletion of that SOP. The sequential number will be followed by two digit Version number which indicates the number of the revision of the respective SOP.

[][]Version No: In case of new SOP, mention “01” in this column. In case of revision, mention number of version in this column.
[][]Superseded: In case of new SOP, mentions “N/A” in this column. In case of revision, SOP No. of old version shall be written in this column.
[][]Page No.: Mention page No. in this column. It shall be mentioned in “Page X of Y” format.
[][]Prepared By (Signature in Blue Ink on Every Page): Signature of a person, who has written the SOP, shall appear in this column. The signature shall be done using a blue ink to identify the copy as master copy.
[][]Checked By (Signature in Blue Ink on Every Page): Signature of Head of SOP Controlling Department /User department head or any concerned reviewer, who has checked the SOP, shall appear in this column.
[][]Agreed By: Signature of Head of other departments excluding SOP owner /User department head or any concerned reviewer, who has checked & agreed the SOP, shall appear in this column.

[][]Define Content of SOP: Every SOP must contain the following standard sections and contents. Guide line to write these contents is in below:
[][]Issue Date: This is the date when the SOP is issued for signature/approval. This should be in the day-month-year (dd-month-yyyy) format i.e. 30-August-2012.
[][]Effective Date: Mention the effective date from which the SOP shall be implemented after proper training. This should be within 7 working days of approval.
[][]Review Date: It will be 36 months from the issue date in day-month-year (dd-month-yyyy) format. However, revision may be made as and when required before schedule.
[][]Review and Approval: This section must include the printed name, signature, job title, and signing date for the following four disciplines:
[][]Prepared by
[][]Checked by
[][]Agreed by( it would be included where necessary)
[][]Approved by
[][]Distribution List: This section will have a list with job title of individual or sectional name to which the SOP will be distributed for execution.
[][]Purpose: The purpose must state why the SOP is needed

[][]Scope: Mention the application of the SOP in this section. It shall describe the extent of areas covered by the SOP. If the same SOP is used in different location, mention the location in the scope of that SOP.
[][]Definition / Abbreviation: Definitions of words, abbreviations, or actions that may not be readily understandable.
[][]Responsibility: Briefly describes the detailed responsibilities of individuals/departments for implementation of the SOP.
[][]Revision Details: In case of revision, point out the specific changes of current version with previous version. For a new SOP the Revision Details text must read: “First issue”.
[][]Annexure: The mandatory features of an annexure are:

Annexure-I: Format of SOP
Annexure-II: SOP Issue Register
Annexure-III: Request for Issuance of Additional copy of SOP
Annexure-IV: Authorization for Discontinuation of SOP

Procedure:

[][]Note: It will be applicable for any SOP of general precautions or operational safety.
[][]The process for developing and managing any SOP includes picking of right format, number generation, drafting, review, approval, issuance, distribution, periodic review, revising, withdrawing, archiving and destruction.
[][]Layout Designing for SOP: Before preparation of a SOP, following preliminary requirements are to be meet:
[][]Format of SOP
[][]Standard Format (Annexure-I) shall be used for preparing any Standard Operating Procedure.
[][]The format of this SOP should be used to maintain the same text fonts, page borders, and general document format as explained here.

ParticularsFont sizeFont Font Style
In Header: Company LogoN/AN/APosition is ‘Left side’
In Header: Company Name14ArialBold, All Letters in Capital, Position is ‘Centered’ (both in Horizontally & Vertically)
In Header: Plant Address08ArialAll words are Regular but “Plant” is in bold. Position is ‘Centered’ (both in Horizontally & Vertically)
SOP Title10ArialBold & Uppercase
Heading10ArialBold
Text10ArialRegular
In footer10ArialBold, Position is ‘Left (indent)’ in Horizontally & ‘Centered’ in Vertically

Page Set Up

Margin:
[][]Top: 0.75
[][]Bottom: 0.75
[][]Right: 0.75
[][]Left: 0.75
[][]Gutter: 0
[][]Header: 0.5
[][]Footer: 0.5
[][]Paper size: A4 size, offset paper
[][]Orientation : Portrait (However landscape orientation may be used for annexure or if required).
[][]Header : Same for all pages [Annexure-I] [][]Footer: Same for all pages except first. In first page there is no footer. [Annexure-I].
[][]Heading of the main content should use appropriate heading number such as 1, 2, 3 etc.
[][]Subheading may be included in any of the content sections using appropriate heading numbering such as 1.1, 1.2 etc.
[][]Further subheading may be included in any of the sub content sections using appropriate heading numbering such as 1.1.1, 1.1.2 etc.
[][]Header & Footer: Each page header must contain the following information:
[][]Title: Mention title of the SOP, which is expressive of the subject of the SOP.

[][]SOP Number: All the SOP numbers must be unique, unambiguous and unanimous. Referencing should be done in such a manner that it reflects either the function or purpose of this SOP. Standard format of SOP number is as – ‘SOP /Sectional Ref/Sequential SOP No. / Version No.’
[][]Sectional Reference is the predefined department/Section code to identify the SOP controlling department.

The following ‘Sectional Ref’ numbers must be used at the time of preparation of SOPs.

[][]Production (General): PRO
[][]Production (Sterile): S-PRD
[][]Packaging (General): PKG
[][]Packaging (Sterile): S-PKG
[][]Warehouse (General): WH
[][]Warehouse (Sterile)S-WH
[][]Quality Assurance (General): QA
[][]Quality Assurance(Sterile)S-QA
[][]Quality Control(General): QC
[][]Quality Control(Sterile): S-QC
[][]Microbiology(General): MIC
[][]Microbiology(Sterile): S-MIC
[][]Product Development(General): PD
[][]Product Development(Sterile):S-PD
[][]Engineering: ENG
[][]HR & Admin: HRD
[][]Supply Chain: SC
[][]Information Technology: IT
[][]Environment, Health & Safety: EHS

A three digit Sequential number shall be assigned to the SOP. This number cannot be reassigned to any other SOP even after deletion of that SOP. The sequential number will be followed by two digit Version number which indicates the number of the revision of the respective SOP.

[][]Version No: In case of new SOP, mention “01” in this column. In case of revision, mention number of version in this column.
[][]Superseded: In case of new SOP, mentions “N/A” in this column. In case of revision, SOP No. of old version shall be written in this column.
[][]Page No.: Mention page No. in this column. It shall be mentioned in “Page X of Y” format.
[][]Prepared By (Signature in Blue Ink on Every Page): Signature of a person, who has written the SOP, shall appear in this column. The signature shall be done using a blue ink to identify the copy as master copy.
[][]Checked By (Signature in Blue Ink on Every Page): Signature of Head of SOP Controlling Department /User department head or any concerned reviewer, who has checked the SOP, shall appear in this column.

[][]Agreed By: Signature of Head of other departments excluding SOP owner /User department head or any concerned reviewer, who has checked & agreed the SOP, shall appear in this column.
[][]Define Content of SOP: Every SOP must contain the following standard sections and contents. Guide line to write these contents is in below:
[][]Issue Date: This is the date when the SOP is issued for signature/approval. This should be in the day-month-year (dd-month-yyyy) format i.e. 30-August-2012.
[][]Effective Date: Mention the effective date from which the SOP shall be implemented after proper training. This should be within 7 working days of approval.
[][]Review Date: It will be 36 months from the issue date in day-month-year (dd-month-yyyy) format. However, revision may be made as and when required before schedule.
[][]Review and Approval: This section must include the printed name, signature, job title, and signing date for the following four disciplines:

[][]Prepared by
[][]Checked by
[][]Agreed by( it would be included where necessary)
[][]Approved by
[][]Distribution List: This section will have a list with job title of individual or sectional name to which the SOP will be distributed for execution.
[][]Purpose: The purpose must state why the SOP is needed.
[][]Scope: Mention the application of the SOP in this section. It shall describe the extent of areas covered by the SOP. If the same SOP is used in different location, mention the location in the scope of that SOP.
[][]Definition / Abbreviation: Definitions of words, abbreviations, or actions that may not be readily understandable.

[][]Responsibility: Briefly describes the detailed responsibilities of individuals/departments for implementation of the SOP.
[][]Revision Details: In case of revision, point out the specific changes of current version with previous version. For a new SOP the Revision Details text must read: “First issue”.
[][]Annexure: The mandatory features of an annexure are:
[][]No annexure can be updated without updating the SOP.
[][]No need to update Annexure during only updating the SOP.

[][]Procedure: This section provides the detailing about the step-wise activities to be performed within a system.
[][]Preparation of SOP:
[][]SOP author will prepare a procedure in clear unambiguous language which describes the process to be conducted against the SOP in sufficient detail that they can be performed in a reproducible, systematic and consistent manner. During preparation of SOP author must consider the following:
[][]Understand the full process first and then write the procedure/SOP.
[][]Write procedure using simple, clear, concise & easy sentences.

[][]Abbreviations must be defined in full on the first occasion of use. All the resources that can give ideas about preparing the procedure shall be explored.

[][]It is preferable to use positive sentence structure in the SOP.
[][]High level process flowcharts or diagrams must be used for clear understand of the process
[][]User Department Head confirms the content, accuracy and detailing of SOP.
[][]Review of the Documents:
[][]The author collect all comments from the review of the document and update the document as appropriate and be able to provide the Approvers with a justification for any comments from key reviewers that are not accepted.

[][]Approval of SOP:
[][]After final verification, All SOP’s must be approved by Manager, Quality Assurance.
[][]Training on SOP:
[][]After final sign off the originator or controlling department will initiate the training program on SOP.
[][]Training must be conducted before the effective date of the SOP.
[][]The originator will inform to Human Resources Department [HR] with a formal request for organizing training.

Issue of SOP:

[][]SOP controlling department will make required photocopies of the SOP from Master SOP as per distribution list.
[][]Put the “CONTROLLED” stamp in blue ink at the top of the right side of each page of the SOP.

[][]Controlling Department issues the SOP for implementation after making necessary entries in the controlled copy issuance record (Annexure-II) at the time of issuing. The record sheet will be attached with master SOP.
[][]Controlling Department will retrieve all controlled copies of the superseded version.
[][]Controlling Department person shall put the “OBSOLETE” stamp (sample is given below) in red colour on each page of the Master SOP of the superseded version. The Controlling

[][]Department shall keep the OBSOLETE MASTER SOP in the master OBSOLETE file.

[][]All other copies of superseded version will be destroyed after keeping a record.
[][]Photocopy of the “CONTROLLED COPY” is not permitted.
[][]Any photocopy that is not having blue stamp of “CONTROLLED” shall not be considered valid for use.
[][]Master SOP will be kept by Quality Assurance department.

[][]There shall be a Master List of all main SOPs and it shall be maintained by Quality Assurance Department.

Implementation:

[][]The user department after receiving “CONTROLLED” copy of the new SOP shall implement the SOP after training.

Periodic review of SOP:

[][]SOP shall be reviewed at least every 3 years. However SOP’s may be revised before the next review date if required.
[][]In case of any change in the SOPs that may affect the product quality a Change Control Proposal shall be raised by the user’s section/department.

Issuance of Additional Copy of SOP:

[][]If an additional copy of SOP is required by any department for non-operational use then QA dept. shall issue an additional copy only after written approval from Manager, quality [][]Assurance. Such requests shall be obtained through the Request Form as per Annexure -III and shall be forwarded through the department head.

Discontinuation of the SOP:

[][]The existing SOP may be discontinued with proper justification and approval of Departmental Head / Manager, Quality assurance. The SOP number of deleted SOP cannot be reassigned to any other SOP. Fill the details for discontinuation of the SOP as per Annexure-IV.
[][]QA person shall retrieve and destroy all the controlled copies of the discontinued SOP after the authorization of Manager, Quality assurance.
[][]QA person shall put the ‘OBSOLETE’ stamp in red color on the every page of the original copies of the discontinued SOP.

Annexure:

Annexure-I: Format of SOP
Annexure-II: SOP Issue Register
Annexure-III: Request for Issuance of Additional copy of SOP
Annexure-IV: Authorization for Discontinuation of SOP
Annexure-V: SOP Index

SOP for SOP Preparation and Handling Procedure Read More »

Atlas Copco Air Compressor & Air Dryer Operation & Maintenance

Atlas Copco Air Compressor , Purpose:

Atlas Copco Air Compressor , The purpose of this SOP is to define the standard operation and maintenance procedure of Atlas Copco Air Compressor and Air Dryer in order to ensure its smooth & trouble-free operation and generation of quality compressed air.

Atlas Copco Air Compressor , Scope:

This Standard Operating Procedure applies to the Atlas Copco Air Compressor (Model: ZT 75) and Air Dryer (Model: CD185+) which is located at the Utility area of Solid Block of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]Air Compressor: An air compressor is a device that converts power (usually from an electric motor) into kinetic energy by compressing and pressurizing the ambient air.

Responsibilities:

[][]The roles and responsibilities are as follows:

Engineering (Validation) Department

[][]Preparing the SOP and revise it when necessary.

Engineering (Maintenance) Department

[][]To provide necessary support for smooth operation & maintenance of the system.
[][]To ensure that the operators are responsible to carry out the operation and maintenance work and regular checking of the critical components and logbooks.
[][]To develop a list of spare parts based on the manufacturer’s recommendations and to forward the list to the Planning and Procurement department with a request to place order as required.

Operators

[][]To operate the Air Compressor according to the SOP.
[][]To fill up the logbooks related to the air compressor.
[][]To do the maintenance according to the check list.

Manager,  Engineering

[][]To ensure that the operation and maintenance of air compressor are done properly.
[][]To approve any maintenance/plans related to the compressor.

Manager, Quality Assurance

[][]To ensure overall implementation of this SOP.

Procedure:

Precautions:

[][]All operation and maintenance work must be done safely in accordance with the requirements of the Plant Safety Statement and the safety notices around the plant. Specific attention must be paid to the following:
[][]Never touch any piping or components of the compressor during operation.
[][]Use only the correct type and size of hose end fittings and connections. When blowing through a hose or air line, ensure that the open end is held securely.

[][] A free end will whip and may cause injury. Make sure that a hose is fully depressurized before disconnecting it.
[][]Do not apply the air to skin or direct an air stream at people. Never use the air to clean dirt from your clothes. When using the air to clean equipment; do so with extreme caution and wear eye protection.
[][]Persons switching on the machines shall take adequate precautions to ensure that there is no one checking or working on the machine.
[][]Never operate the machine when there is a possibility of taking in flammable or toxic fumes, vapors or particles.

[][]Never operate the machine below or in excess of its limit ratings.
[][]Keep all bodywork doors shut during operation.
[][]All maintenance work shall only be undertaken when the machine has cooled down.
[][]Before removing any pressurized component, effectively isolate the machine from all sources of pressure and relieve the entire system of pressure.
[][]Never use flammable solvents or carbon tetrachloride for cleaning parts. Take safety precautions against toxic vapors of cleaning liquids.
[][]Never use a light source with open flame for inspecting the interior of a machine, pressure vessel, etc.
[][]Make sure that no tools, loose parts or rags are left in or on the machine.
[][]Do not walk or stand on the roof of the unit.

System Description:

The Atlas Copco Air Compressor and Air Dryer manufactured by Atlas Copco has a capacity of 10.4 m3/min.
[][] Air drawn through an air filter is compressed in low-pressure compressor element and discharged to the intercooler.
[][]The cooled air is further compressed in high-pressure compressor element and discharged through silencer and after coolers.
[][]A check valve is provided downstream of the silencer.
[][]The compressed air leaves the compressor via the air outlet.
[][]The compressor delivers oil-free, pulsation-free air.
[][]This is an air cooled type compressor which is facilitated with air filter, moisture trap, high pressure and low pressure safety valve, desiccant type dryer system etc.
[][]After being compressed in compressor the oil free compressed air will be stored in a receiver tank.
[][]Air will be dried in the desiccant type dryer and then distributed through pipe line to the different production facility.

Operating Procedure:

Operation of compressor:

[][]Initial Start-up of compressor:
[][]Tight up all the flanges, nuts and bolts as instructed in the instruction manual of the compressor.
[][]Check that the gear casing is filled with oil; the level should be in the middle of sight-glass.
[][]The electrical installation must be earthed and protected by fuses in all phases. An isolating switch must be provided.
[][]Switch on the voltage. Start the compressor and stop it immediately. Check for correct direction of rotation (Clockwise) while the motor is coasting to a stop.
[][]An arrow on the gear casing indicates the correct rotation direction. If the rotation direction is wrong, switch off the voltage and reverse two incoming electric lines.
[][]Check the rotation direction of the fan motor. If the rotation direction is wrong, switch off the voltage and reverse the motor’s electrical connection.

[][]Open the air outlet valve.

[][]Switch on the voltage and check that voltage on LED (2) lights up.
[][]Press start button (1). The compressor starts running and automatic operation LED (3) lights up.

Be careful about the following:

[][]When the compressor is stopped and automatic operation LED (3) is alight, the compressor may start automatically.
[][]If the start/stop timer is active, the compressor may start automatically, even if it was stopped manually.

During Operation:

[][]Daily check the display (2) for readings and messages. Normally, the main screen indicates the compressor outlet pressure, the status of the compressor and the functions of the keys below the display.
[][]Always check the display and remedy the trouble if alarm LED (3) is alight or blinks.
[][]Regularly check the actual compressor status by pressing the down key from the main screen.
[][]The Operational Log Sheet (Annexure – I) of air compressor and dryer will be filled up on every hour by the operator. Photocopy of all the approved forms will be used where easily applicable.

[][]For the cases where computer generated copies are relatively easy to handle, the exact format of the approved form can be used(except the approval sign) with the following notes as footer:
“This is a computer generated report. The format is as per the original approved form.”

Stopping Procedure:

[][]Frequently stopping the compressor using the emergency stop button may damage the compressor; only use the emergency stop button in case of emergency.

[][]Press the stop button (1): the compressor will stop and LED (2) will go out.
[][]Close the air outlet valve.
[][]To stop the compressor immediately, press emergency stop button (S2).

 Taking out of operation:

[][]Close the air outlet valve and stop the compressor.
[][]Switch off the voltage and disconnect the compressor from the mains.
[][]Shut down and depressurize all the parts.
[][]Drain oil and condensate circuits.
[][]Disconnect the compressor condensate piping from the condensate drain.

Operation of Air Dryer:

[][]Initial start-up
[][]To start up the dryer for the first time or after a long period of standstill, proceed as follows:
[][]Open the bypass valves of the dryer.
[][]Close the air supply from the compressor towards the dryer by closing the external inlet valve.
[][]Close the external outlet valve.
[][]Remove the silencers to prevent the silencers from getting clogged by the desiccant and wear a dust mask, safety glasses and ear protection. (This is only required at initial start-up or after the desiccant was replaced).
[][]Start the compressor and wait for pressure.
[][]Slowly open the external inlet valve.
[][]Check the connections of the dryer for air leaks and remedy if necessary.
[][]Switch the dryer on by putting main switch S1 in position I.
[][]Let the dryer operate for several hours with the external outlet valve closed.
[][]In case the silencers were removed, refit the silencers.
[][]Gradually open the external outlet valve.
[][]Close the bypass valves of the dryer.

Normal start

[][]If the dryer has not been used for more than 3 months, refer to previous section, In all other cases proceed as follows:
[][]Cut off the air supply from the compressor towards the dryer by closing the external inlet valve.
[][]Close the external outlet valve between the dryer and the dry air consumer.
[][]Start compressor and slowly open the external inlet valve.
[][]Switch the dryer on by putting main switch in position I.
[][]Gradually open the air outlet valve.
[][]Close the bypass valves of the dryer.
[][]Close the external inlet valve in case the compressor needs to be restarted. The high air speed in the start-up phase of the compressor may damage the desiccant.

Shutdown Procedure of Dryer:

[][]To stop the dryer, proceed as follows:
[][]Open the bypass valves of the dryer so that the application will still receive compressed air.
[][]Close the external inlet valve between the compressor and the dryer and the external outlet valve between the dryer and the dry air consumer.
[][]Let the dryer operate for a period without consumption, to depressurize the vessels.
[][]Switch off the dryer by putting main switch to position 0.
[][]If the dryer is stopped for a longer period, keep the external inlet and outlet valve closed to avoid the moisture from entering the dryer.
[][]Under no circumstances must compressed air be allowed to flow through the dryer when the electrical power is switched off. This will result in terminal failure of the desiccant material; causing regeneration will no longer be possible.

Maintenance Procedure:

Safety Instruction:

[][]Hang the Maintenance tag prior to any maintenance activity.
[][]Use protective clothing.
[][]Use proper tools.
[][]Isolate the system electrically and mechanically prior to maintenance.

General Instruction:

[][]Plan and procure spares and manpower prior to the maintenance works.
[][]Only trained personnel are to be engaged in maintenance work.
[][]After finishing the maintenance work, the area & the equipment should be cleaned & tagged out.
[][]Functional/operational checks are to be conducted after maintenance works have been done.
[][]Maintenance Log Book (Annexure – II) has to be filled up by the operator after performing scheduled maintenance.

Maintenance Program:

Daily Maintenance

[][]Clean the machine exterior and its surroundings.
[][]Check that condensate is discharged during loading.
[][]Check the oil level. Before starting, the level should be in the middle of the sight-glass.
[][]Check the display panel for information and service messages.

Weekly Maintenance

[][]Clean the inner side of the machine.
[][]Clean the air filters thoroughly.

Monthly Maintenance

[][]Check for possible leaks.

Quarter Yearly

[(3 months) Maintenance] [][]Check coolers, clean if necessary.

Maintenance after 2000 hrs

[][]Check for damaged wiring or loose connections.
[][]Replace the air filter cartridge.
[][]Replace the oil filter cartridge.
[][]Check/replace the cooling air inlet filter.
[][]Replace the inlet and outlet filter cartridges of Air Dryer.
[][]Change the lubricating oil.

Maintenance after 4000 hrs

[][]Tighten the bolted connections.
[][]Tighten all the connecting terminals in the switch cabinet/electric motor.
[][]Test the safety valve function.
[][]Replace the silencers of Air Dryer.

Maintenance after 8000 hrs

[][]Perform the maintenance as it is in the Yearly maintenance schedule.
[][]Replace worn parts.

Maintenance after 40000 hrs

[][]Replace desiccant of air dryer.
[][]Revision of inlet valves and actuator.
[][]Replace the check valves.

Other Maintenance

[][]Oil and Oil Filter Change Procedure
[][]Run the compressor until warm.
[][]Press stop button, wait until the compressor has stopped, press emergency stop button (S2) and switch off the voltage to the compressor.
[][]Remove filler plug. Drain the compressor sump by opening drain valve. Close the valve after draining.
[][]Drain the oil cooler by removing its drain plug and vent plug.
[][]Drain the oil of the compressor elements. Yellow-painted drain plugs are provided on both elements.
[][]Remove the oil filter. Clean the filter seat, oil the gasket of the new filter and screw it into place until the gasket contacts the seat. Then tighten by hand.
[][]Fill the compressor sump to the middle of the oil level sight-glass with oil as specified in “Oil specifications”. Reinstall the filler plug.
[][]Switch on the voltage. Unlock the emergency stop button.
[][]Run the compressor for a few minutes. Stop the compressor. If necessary, top up the gear casing with oil to the middle of the sight-glass.

Air Filter Cleaning Procedure:

[][]Stop the compressor and switch off the voltage to the compressor.
[][]Remove the filter.
[][]Clean the filter by passing compressed air through the filter.
[][]After carrying out the service actions of the related service plan, the service warning must be reset.

Annexure:

Annexure – I: Operational Log Sheet.
Annexure – II: Maintenance Log Book of Atlas Copco Air Compressor and Air Dryer.

Atlas Copco Air Compressor & Air Dryer Operation & Maintenance Read More »

Lupamat Air Compressor And Air Dryer Operation And Maintenance

Lupamat Air Compressor,Purpose:

Lupamat Air Compressor, The purpose of this SOP is to define the standard operation and maintenance procedure of Air Compressor manufactured by Lupamat in order to ensure its smooth & trouble-free operation and generation of quality compressed air.

Lupamat Air Compressor, Scope:

This Standard Operating Procedure applies to the Lupamat Air Compressor of Model – LKV 37/10MI, which is located at the Utility area of General Block of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]Air Compressor: An air compressor is a device that converts power (usually from an electric motor) into kinetic energy by compressing and pressurizing the ambient air.

Responsibilities:

[][]The roles and responsibilities are as follows:

Engineering (Validation) Department

[][]Preparing the SOP and revise it when necessary.

Engineering (Maintenance) Department

[][]To provide necessary support for smooth operation & maintenance of the system.
[][]To ensure that the operators are responsible to carry out the operation and maintenance work and regular checking of the critical components and logbooks.
[][]To develop a list of spare parts based on the manufacturer’s recommendations and to forward the list to the Planning and Procurement department with a request to place order as required.

Operators

[][]To operate the Air Compressor according to the SOP.
[][]To fill up the logbooks related to the air compressor.
[][]To do the maintenance according to the check list.

Procedure:

Precautions:

[][]All operation and maintenance work must be done safely in accordance with the requirements of the Plant Safety Statement and the safety notices around the plant. Specific attention must be paid to the following:
[][]Never touch any piping or components of the compressor during operation.
[][]Use only the correct type and size of hose end fittings and connections. When blowing through a hose or air line, ensure that the open end is held securely. A free end will whip and may cause injury. Make sure that a hose is fully depressurized before disconnecting it.
[][]Do not apply the air to skin or direct an air stream at people. Never use the air to clean dirt from your clothes. When using the air to clean equipment; do so with extreme caution and wear eye protection.
[][]Persons switching on the machines shall take adequate precautions to ensure that there is no one checking or working on the machine.
[][]Never operate the machine when there is a possibility of taking in flammable or toxic fumes, vapors or particles.

[][]Never operate the machine below or in excess of its limit ratings.
[][]Keep all bodywork doors shut during operation.
[][]All maintenance work shall only be undertaken when the machine has cooled down.
[][]Before removing any pressurized component, effectively isolate the machine from all sources of pressure and relieve the entire system of pressure.
[][]Never use flammable solvents for cleaning parts. Take safety precautions against toxic vapors of cleaning liquids.
[][]Never use a light source with open flame for inspecting the interior of a machine, pressure vessel, etc.
[][]Make sure that no tools, loose parts or rags are left in or on the machine.
[][]Do not walk or stand on the roof of the unit.

System Description:

The air compressor manufactured by Lupamat has a capacity of 5.03 m3/min.
[][] Air drawn through an air filter is mixed with the oil and compressed in screw type compressor.
[][] The compressed air – oil mixture is then passed through the oil separator to separate the oil.
[][]This compressed air is discharged through silencer and after coolers.
[][]The compressed air leaves the compressor via the air outlet.
[][]This is an air cooled type compressor which is facilitated with air filter, moisture trap, high pressure and low pressure safety valve, desiccant type dryer system etc.
After being compressed in compressor the compressed air will be stored in a receiver tank.
[][]Air will be dried in the desiccant type dryer and then distributed through pipe line to the different production facility.

Operating Procedure:

Operation of compressor:

[][]Initial Start-up of compressor:
[][]Tight up all the flanges, nuts and bolts.
[][]Check the oil level inside the tank.
[][]The electrical installation must be earthed.
[][]Close the discharge valve before initial start – up.
[][]Switch on the voltage. Start the compressor by pressing Start Button and stop it immediately.
[][]Check for correct direction of rotation (Clockwise) while the motor is coasting to a stop.
[][]If the rotation direction is wrong, switch off the voltage and reverse two incoming electric lines.
[][]Check the rotation direction of the fan motor. If the rotation direction is wrong, switch off the voltage and reverse the motor’s electrical connection.

Start-up Procedure of compressor:

[][]Open the air outlet valve.
[][]Switch on the main circuit breaker.
[][]Press the Start button. The compressor starts running in automatic mode.

During Operation:

[][]Daily check the display for readings and messages. At the left middle of the main screen the line pressure, air / end pressure, air/oil temperature can be seen. At the middle of right side of the screen total working time, load working time information and the remaining time up to general service maintenance time.
[][]Always check the display and remedy the trouble if alarm is alight or blinks.
[][]The Operational Log Sheet (Annexure – I) of air compressor and dryer will be filled up on every hour by the operator.
[][]Photocopy of the all the approved forms will be used where easily applicable.
[][]For the cases where computer generated copies are relatively easy to handle, the exact format of the approved form can be used(except the approval sign) with the following notes as footer:
“This is a computer generated report. The format is as per the original approved form.”

Stopping Procedure:

[][]Press the stop button; the compressor will stop when the outlet pressure is under 1 bar.
[][]If the pressure does not come under 1 bar within 5 minutes the compressor will stop by giving a failure alarm “the compressor cannot be stopped”.
[][]Close the air outlet valve.
[][]Cut the electricity from the main power. When shutting down after a normal day operation, empty out any water that may have stayed within the air tank.
[][]To stop the compressor immediately, press emergency stop button.
[][]Frequently stopping the compressor using the emergency stop button may damage the compressor; only use the emergency stop button in case of emergency.
[][]The compressor cannot be started without resetting the emergency switch.

Operation of Air Dryer:

Starting Procedure

[][]Hold down on-off button for 3 seconds.
[][]With the first start, all leds on the front panel flash one by one.
[][]At first, the hot air gets into dryer, +4 °C or +8°C led flashes. Then refrigerating compressor starts to work and related led flashes.
[][]Condenser fan unit starts only if the refrigerating compressor is running and/or condenser fan temperature is higher than +30°C.
[][] It switches itself “stop” when condenser fan temperature gets lower than +20°C or refrigerating compressor stops.
[][]Cooling process continues until temperature gets down to +2°C and condenser motor stops. Dryer switches itself “STOP” and Because of thermal storage feature of heat exchanger, keeps the heat for a while.
[][]When the heat rises up to +4°C motor starts again. System continues in this way.

Stopping Procedure of Dryer:

[][]To stop the dryer, proceed as follows:
[][]Close the external inlet valve between the compressor and the dryer and the external outlet valve between the dryer and the dry air consumer.
[][]Switch off the dryer by pressing ON/OFF button.
[][]If the dryer is stopped for a longer period, keep the external inlet and outlet valve closed to avoid the moisture from entering the dryer.

Maintenance Procedure:

Safety Instruction:
[][]Hang the Maintenance tag prior to any maintenance activity.
[][]Use protective clothing.
[][]Use proper tools.
[][]Isolate the system electrically and mechanically prior to maintenance.

General Instruction:

[][]Plan and procure spares and manpower prior to the maintenance works.
[][]Only trained personnel are to be engaged in maintenance work.
[][]After finishing the maintenance work, the area & the equipment should be cleaned & tagged out.
[][]Functional/operational checks are to be conducted after maintenance works have been done.
[][]Maintenance Log Book has to be filled up by the operator after performing scheduled maintenance.

Maintenance Program:

Daily Maintenance

[][]Clean the machine exterior and its surroundings.
[][]Check that condensate is discharged during loading.
[][]Check the oil level. Before starting, the level should be in the middle of the sight-glass.
[][]Check the display panel for information and service messages.

Weekly Maintenance

[][]Clean the inner side of the machine.
[][]Clean the air filters thoroughly.
[][]Check for possible leaks.
[][]Clean the condenser unit of Air Dryer with compressed air.
[][]Clean the cooler surface.
[][]Check the tightness of v-belt.

After 3000 hrs

[][]Clean the air filter elements.
[][]Check the viscosity of the oil and change it if necessary.
[][]Check for oil leakage.

After 5000 hrs

[][]Check for damaged wiring or loose connections.
[][]Check and replace the air hoses if necessary.
[][]Check and replace the oil hoses.
[][]Clean the air/oil separator tank.

After 10000 hrs

[][]Clean the intake air filter and change it if necessary.
[][]Clean the intake control valve.
[][]Clean the intake control valve o-ring and rubber pad and change it if necessary.
[][]Clean the air/oil pipe gasket and change it if necessary.
[][]Check the V-belt and change it if necessary.

After 20000 hrs

[][]Replace the electric motor bearings if it is necessary.

Annexure:

Annexure – I: Operational Log Sheet.
Annexure – II: Maintenance Log Book of Air Compressor and Air Dryer.

Lupamat Air Compressor And Air Dryer Operation And Maintenance Read More »

Diesel Generator Operation and maintenance

Diesel Generator, Purpose

Diesel Generator, The purpose of this SOP is to describe the procedure of operation and maintenance of the 1000 KVA diesel generator which is installed in the Generator room of Solid Block of XX Pharmaceuticals Ltd.

Diesel Generator, Scope

This SOP applies to the Cummins generator of Model No.: QST30-G4 and capacity 1000 KVA which is located at General block of XX Pharmaceuticals.

Definitions / Abbreviation:

[][]EHS : Environment Health and Safety
[][]PPE : Personal Protective Equipment
[][]SOP : Standard Operating Procedure

Responsibilities:

[][]The roles and responsibilities are as follows

Engineering ( Validation) Department

[][]To prepare the SOP & revise it when necessary.

Engineering (Maintenance) Department

[][]To provide necessary support for smooth operation & maintenance of the system.
[][]To ensure that the operators are responsible to carry out the operation and maintenance work and regular checking of the critical components and logbooks.
[][]To develop a list of spare parts based on the manufacturer’s recommendations and to forward the list to the Planning and Procurement department with a request to place order as required
[][]Engage technician/mechanic/operator/supplier in repair and maintenance work

Operators

[][]To operate the generator according to the SOP.
[][]To fill up the logbooks related to the Generator.
[][]To do the maintenance according to the check list.

Procedure

Precautions:

[][]All maintenance work must be carried out safely in accordance with the requirements of the Plant Safety Requirements and the EHS safety notices must be displayed around the plant. Specific attention must be paid to the following:
[][]Personal protective equipment (PPE) and clothing appropriate to the job must be worn.
[][]Hearing protection must be used.
[][]Equipment must be electrically isolated and locked out where possible.
[][]Ensure the control panel is switched off before carrying out any check.
[][]Do not smoke when put fuel in the tank.
[][]Clean away fuel which has been spilt. Material which has been contaminated by fuel must be moved to a safe place.
[][]Do not make adjustment that doesn’t understand.
[][]Do not remove the filler cap or any component of the cooling system while the engine is hot and while the coolant is under pressure, because dangerous hot coolant can be discharged.
[][]Turbochargers operate at high speed and at high temperatures. Keep fingers, tools and debris away from the inlet and outlet ports of the turbocharger and prevent contact with hot surfaces.
[][]Use extreme care if emergency repairs must be made in adverse conditions.
[][]The fuel injector units are actuated by high pressure engine lubricating oil. Do not remove any component of the high pressure system while the engine oil is under pressure, because dangerous oil can be discharged.
[][]Maintenance activity must be carried out by trained technician/operators.
“Under Maintenance” be displayed in a prominent position on a machine, equipment or facility undergoing maintenance work.

Engine Starting Procedure

Pre-Start Check

[][]Before the engine is started the operator should understand fully the reason for the controls and their use. The following check should be done before engine start.
[][]Make a general visual inspection on the engine and alternator. Check if there is any breakage, crack, leakage or looseness.
[][]Check the battery electrolyte level-fill with distilled water as necessary.
[][]Check that there is sufficient coolant level and if necessary, add the correct coolant
[][]Check that there is sufficient lubricating oil in the sump & Viscosity and, if necessary add lubricating oil.
[][]Fill the fuel tank with fuel of the correct specification.
[][]Check the air filter and its connection.
[][]Check the all electrical connections are tight.
[][]Check the condition and tension of the fan end engine alternator belts-tighten as necessary.
[][]Check all hoses for loose connections or deterioration tighten or replace as necessary.
[][]Check the battery connection cables. Take care to tighten the loosened battery terminals with spanner and, cover with special substance and keep clean in order to avoid oxidation
[][]Take out foreign materials such as keys, tools, cleaning wool, papers etc. on the engine and the Alternator.

Engine Start

[][]Reset the emergency stop.
[][]Press the reset button.
[][]Start key turn to the “ON” Position.
[][]After start key turn to “ON” position following are checked:
[][]Check for any abnormal noise or vibration.
[][]Check for fluid leakage or leaks in the exhaust system.
[][]Check the control panel for indications of abnormal operations, particularly abnormally high temperature or low oil pressure. The oil pressure should be in the normal range within about 10 seconds of starting.
[][]Switch the alternator circuit breaker to “ON” (Handle Up).

Caution:

[][]Load can now be applied to the generating set (Normally 2-3 minutes wait from pressing the start button).
[][]The maximum step load can be 70%-100% of rated power depending on the generating set model. Typically we run 80% of rated load.
[][]Do not operate the engine at high speeds without a load.
[][]Do not overload the engine.

Engine Stopping Procedure

[][]Turn off the load by switching output circuit breaker to “OFF” (Handle Down).
[][]Allow the generating set to run without load.
[][]After 2-3 minutes the key turn to the “OFF” position.
[][]In case of an emergency where immediate shutdown is necessary, the emergency stop push button should be pushed immediately without discounting the load.

Preventive Maintenance Planning

[][]The preventive maintenance periods apply to average conditions of operation. The schedule which follows must be applied at the Interval (hours or months) which occur first.

Daily or every 20 Hours after

[][]Visually inspect engine, generator, transfer switch and Control panel.
[][]Clean the machine exterior and its surroundings.
[][]Ensure that the coolant is at the correct level.
[][]Check Oil, Water and fuel leaks.
[][]Check the amount of lubricating oil in the sump.
[][]Check the fuel level in the fuel tank.
[][]Check the lubricating oil pressure at the panel display.
[][]Battery charge level.
[][]Drain Fuel/Water separator.
[][]Inspect the engine fan blades.
[][]Inspect the drive belt.
[][]Drain water from the fuel pre-filter.
[][]Check the intercooler and the coolant radiator for debris.

Weekly Maintenance

[][]Repeat Daily Check.
[][]Fuel level in main tank.
[][]Fuel lines and connections.
[][]Adequate fresh air to engine.
[][]Check hose and connections.
[][]Battery charging alternator belts.
[][]Inspect the engine fan blades.
[][]Inspect the fan belt.
[][]Check oil level (Governor Housing).
[][]Check exhausts leakage.
[][]Tighten connections.
[][]Check Panel display.
[][]Tighten covers.
[][]Check output voltage and frequency
[][]Operation under load.
[][]No unusual sounds.
[][]Terminals and connections normal color.
[][]Doors closed securely.

Monthly Maintenance

[][]Repeat weekly check
[][]Clean the air filters.
[][]Check All fittings, Clamps, fasteners etc
[][]Check generator air outlet

After 6 Months or every 200 Hours

[][]Repeat weekly check
[][]Clean air filters
[][]Change, lubricating oil
[][]Change the lubricating oil filters.
[][]Change, lubricating oil filters
[][]Change, fuel filters
[][]Drain sediment from main tank
[][]Change, lubricating oil
[][]Check, antifreeze
[][]Governor lubricate with grease, bearing of the fan hub.
[][]Check operating alarms and safeties

After 12 Months or 800 Hours

[][]Repeat Maintenance after 200 Hours.
[][]Check and adjust if necessary, the antifreeze.
[][]Test the level of coolant conditioner and adjust if necessary.
[][]Check the condition of the drive belt.
[][]Change the engine lubricating oil.
[][]Change the canister of the lubricating oil filter.
[][]Change the air filter (or earlier if in extremely dusty conditions).
[][]Clean or renew the air filter element Check for damaged wiring or loose connections.
[][]Check radiator hoses for wear and cracks.
[][]Check exterior of radiator for obstructions.
[][]Clean engine.
[][]Generator rotor and stator with compressed air.
[][]Check water circulating pump.
[][]Check Circuit breakers and fuse holders.
[][]After 24 Months or 2,000 Hours
[][]Check the turbocharger bearing clearance
[][]Check the exhaust restriction
[][]Check the valves settings
[][]Check the injectors settings
[][]Check vibration damper
[][]Clean Turbocharger compressor wheel and diffuser.

After every 10000 hours

[][]Overhauling of full generator.
[][]Ensure that the turbocharger impeller and the turbocharger compressor casing are cleaned.
[][]Ensure that the alternator, the starter and the turbocharger are checked.

Annexure

Annexure-I: Maintenance logbook of 1000 KVA diesel generator
Annexure-II : Log sheet for 1000 KVA diesel generator

Diesel Generator Operation and maintenance Read More »

Purified Water Generation Plant Automatic Operation

Purified Water, Purpose:

Purified Water  , The purpose of this SOP is to define the Automatic Operation of Purified Water Generation Plant manufactured by Watertown, China in order to ensure its smooth & trouble-free operation and generation of qualified purified water.

Purified Water, Scope:

This Standard Operating Procedure applies to the PW plant manufactured by Watertown, China, which is located at the Utility area (roof top) of Solid Block of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]PW: Purified Water.
[][]HMI: Human Machine Interface.
[][]RO: Reverse Osmosis.
[][]EDI: Electro De Ionizer.

Responsibilities:

[][]The roles and responsibilities are as follows:

Engineering (Validation) Department

[][]Preparing the SOP and revise it when necessary.

Engineering (Maintenance) Department

[][]To provide necessary support for smooth operation of the system.
[][]To ensure that the operators are responsible to carry out the operation and fill up the logbooks.

Operators

[][]To operate the PW plant according to the SOP.
[][]To fill up the logbooks related to the PW plant.

Manager, Engineering

[][]To ensure that the operation of PW plant are done properly.

Manager, Quality Assurance

[][]To approve the SOP.
[][]To ensure overall implementation of this SOP.

Procedure:

Precautions:

[][]All operational work must be done safely in accordance with the requirements of the Plant Safety Statement and the safety notices around the plant. Specific attention must be paid to the following:
[][]Use Personal Protective Equipment during handling of any kind of chemical.
[][]Be careful about the hot water and steam line.
[][]Ensure all the utilities before doing any operation.

System Description:

[][]The PW plant manufactured by Watertown has a capacity of 3000 L/hr. The plant has Raw water pretreatment and RO/EDI sections.
[][]In Raw water pretreatment portions the water is filtered through Multi Grade Filter and Active Carbon Filter respectively. After that, the water is softened with the softeners.
[][]There are two softeners of which one stands by while running another one. The softeners are regenerated by Brine solution. There are two dosing systems in pretreatment section.
[][]One is Clotech (NaClO) and another is Sodium Meta Bi Sulphite (SMBS) dosing.
[][]The NaClO dosing is used to add Chlorine which acts as a disinfectant. This chlorine is removed in the Active Carbon Filter.
[][]The SMBS dosing is used after active carbon filter to remove the remaining chlorine.
[][]After being softened, the water is treated through two stage Reverse Osmosis (RO) system and Electro De Ionizer (EDI).
[][]Finally, the purified water is stored in the PW storage tank.
[][]Two dosing systems are used in this section: Anti Silicant and NaOH dosing.
[][]NaOH dosing is used to control the pH and anti silicant dosing is used to reduce the silica from the water.

Operating Procedure:

[][]Automatic operation of PW plant:

Starting of PW plant:

[][]Switch on the main breaker to supply electrical power of the plant.
[][]Ensure compressed air and other utilities to run the plant.
[][]The HMI becomes ON and following screen will appear.
[][]Press Enter on that screen.
[][]Then the following screen will appear.
[][]Press “Parameter setting**” button to check the parameters and a box will appear for user ID and Password.
[][]Then the screen will appear to see the parameters. Press “setting2” to see the other parameter settings
[][]Then the screen will appear.
[][]Press the “Pretreatment Flowchart” button and screen for pretreatment flowchart will appear.
[][]Press the “Auto off” button. So, the system will be operated sequentially in automatic mode. In automatic mode the Multi Grade Filter and Active Carbon Filter will be reversely washed and then the RO will be washed.
[][]The softener will be regenerated automatically when the water flow rate is 100 Ton.

[][]After completing reverse washing normal production of PW will start.

During Operation:

[][]To see any alarm press the “Alarm status” button in . Following screen will appear:

[][]By pressing the button “ ” the alarms will be acknowledged and stored in the alarm history. All the alarms in the alarm history can be watched in the “History Alarm” section by pressing the Up and Down arrow.
[][]There is an online data logger which logs the conductivity of water after softener, 1st RO, 2nd RO and EDI.
[][]The real time curve can be seen by pressing the “Real Time Curve” button.
[][]The Daily Operational Log Sheet (Annexure – I) of PW plant will be filled up on every hour by the operator. Photocopy of all the approved forms will be used where easily applicable. For the cases where computer generated copies are relatively easy to handle, the exact format of the approved form can be used(except the approval sign) with the following notes as footer:

“This is a computer generated report. The format is as per the original approved form.”

Stopping procedure of PW plant:

[][]To stop the plant press “Auto on” button in the “Pretreatment Flowchart status” screen.
[][]Switch off the main breaker to cut the electricity.
[][]Close the line of compressed air and other utilities.

Annexure:

Annexure – I: Daily Operational Log Sheet of PW Plant.

Purified Water Generation Plant Automatic Operation Read More »

Active Carbon Filter, RO & EDI Sanitization

Active Carbon Filter, Purpose:

Active Carbon Filter, The purpose of this SOP is to define the procedure of sanitization of Active Carbon Filter, RO and EDI of Purified Water Generation Plant manufactured by Watertown in order to ensure its smooth & trouble-free operation and generation of qualified purified water.

Active Carbon Filter, Scope:

This Standard Operating Procedure applies to the PW plant manufactured by Watertown, which is located at the Utility area (roof top) of Solid Block of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]PW: Purified Water.
[][]HMI: Human Machine Interface.
[][]ACF: Active Carbon Filter.
[][]RO: Reverse Osmosis.
[][]EDI: Electro De Ionizer.

Responsibilities:

[][]The roles and responsibilities are as follows:

Engineering (Validation) Department

[][]Preparing the SOP and revise it when necessary.

Engineering (Operation & Maintenance) Department

[][]To provide necessary support for smooth operation of the system.
[][]To ensure that the operators are responsible to carry out the operation and fill up the logbooks.

Operators

[][]To sanitize the ACF, RO and EDI according to the SOP.
[][]To fill up the logbooks.

Manager, Engineering

[][]To ensure that the operation of PW plant are done properly.

Manager, Quality Assurance

[][]To approve the SOP.
[][]To ensure overall implementation of this SOP.

Procedure:

Precautions:

[][]All operation work must be done safely in accordance with the requirements of the Plant Safety Statement and the safety notices around the plant. Specific attention must be paid to the following:
[][]Use Personal Protective Equipment during handling of any kind of chemical.
[][]Be sure that the steam line is insulated.
[][]Do not touch the hot water pipe line with bare hands.
[][]Check that there is no leakage in the steam or hot water line.
[][]Ensure all the utilities before doing any operation.
[][]Ensure that the water level in the water storage tank is at least 35%.

Framework Description:

[][]The PW plant made by Watertown has a limit of 3000 L/hr. The plant has Raw water pretreatment and RD/EDI areas.
[][] In pretreatment segment crude water is sifted through MGF and ACF separately.
[][] Then, at that point, this crude water is gone through the conditioner to lessen the hardness and is at long last treated with the RO and EDI to get the refined water of wanted determinations.
[][]The disinfection of ACF, RO and EDI is finished by utilizing heated water at a temperature of around 80°C.
[][] There are two hotness exchangers in pretreatment area and RO/EDI segment to create the boiling water with the assistance of modern steam.
[][]After disinfection of RO and EDI cooling is done at a temperature of 30 ± 5°C.

Automatic Sanitization Procedure:

Sanitization of ACF:

[][]Close the manual butterfly valve V47-03.
[][]Switch on the main breaker to supply electrical power of the plant.
[][]Ensure compressed air and other utilities to run the plant.
[][]The HMI becomes ON and following screen will appear.

Press Enter on that screen.

[][]Then the following screen will appear. Press “Parameter setting**” button to check the parameters sanitization and a box will appear for user ID and Password.
[][]Then the following screen will appear to see the parameters. Press “setting2” to see the other parameter settings.
[][]Then the screen will appear.
[][]Press the “Exit” button to go to the menu navigation page
[][]Press the “sanitization***” button and give user ID and password to go to the sanitization page.
[][]In the sanitization page press the “Auto ON” button for Automatic operation.
[][]In the sanitization page press “Carbon filter Sanitization” for sanitization of ACF.
[][]Then the following screen will appear. Press the “Carbon filter Sanitization OFF” button to start the sanitization automatically. Normally the sanitization temperature is approx. 80°C for a period of 60 mins.
[][]During sanitization fill up the operation log sheet (Annexure – I).
[][]Natural cooling procedure is used to cool the ACF after sanitization.

Sanitization of 1st stage RO:

[][]Close the manual butterfly valve V50-22.
[][]In the sanitization page (Figure 06) press the “RO I Sanitization” button. Then the following screen will appear. Press “RO I Sanitization OFF” button on that screen to sanitize the 1st stage RO automatically.
[][]The sanitization temperature of 1st RO is as 80 ± 3°C for 60 mins.
[][]After doing sanitization cooling is done at a temperature of 30 ± 5°C by flowing cooling water.
[][]Fill up the operational log sheet (Annexure – I) during sanitization.

Sanitization of 2nd stage RO:

[][]In the sanitization page (Figure 06) press the “RO II Sanitization” button. Then the following screen will appear. Press “RO II Sanitization OFF” button on that screen.
[][]Cooling procedure is as same as it is for 1st stage RO.

Sanitization of EDI:

[][]Close the manual diaphragm valve of bypass line of membrane contactor.
[][]In the sanitization page (Figure 06) press the “EDI Sanitization” button. Then the following screen will appear. Press “EDI Sanitization OFF” button on that screen.
[][]After sanitization RO and EDI are cooled down to 30°C ± 5°C by supplying cooling water.
[][]Fill up the operational log sheet during whole sanitization and cooling period.

Annexure:

Annexure – I: Operational Log Sheet for Sanitization of ACF, RO and EDI

Active Carbon Filter, RO & EDI Sanitization Read More »

Chiller Operation and Maintenance

Chiller Operation , Purpose

Chiller Operation, The purpose of this SOP is to define the operation and maintenance procedure of Chillers of XX Pharmaceuticals Ltd.

Chiller Operation , Scope

This SOP applies to the Chillers manufactured by Trane, USA which is located at the roof top area of Sterile and Sterile blocks of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]EHS: Environment Health and Safety.
[][]PPE: Personal Protective Equipment.
[][]SOP: Standard Operating Procedure.
[][]AHU: Air Handling Unit.

Responsibilities:

[][]The roles and responsibilities are as follows

Engineering ( Validation) Department

[][]To prepare the SOP & revise it when necessary.

Engineering (Maintenance) Department

[][]To provide necessary support for smooth operation & maintenance of chillers.
[][]To ensure that the operators are responsible to carry out the operation and maintenance work and regular checking of the critical components and logbooks.
[][]To engage technician/mechanic/operator/supplier in repair and maintenance work.

Operators/Technician

[][]To operate the chiller according to the SOP.
[][]To fill up the logbooks related to the Chiller.
[][]To do the maintenance job according to the schedule.

Head of Engineering

[][]To ensure that the operation and maintenance of Chiller are done properly.
[][]To approve any maintenance/plans related to the Chiller.

Head of Quality Assurance

[][]To approve this SOP
[][]To ensure overall implementation of this SOP.

Procedure

Precautions:

[][]All maintenance work must be carried out safely in accordance with the requirements of the Plant Safety Requirements and the EHS safety notices must be displayed around the plant. [][]Specific attention must be paid to the following:
[][]Personal protective equipment (PPE) and clothing appropriate to the job must be worn.
[][]Equipment must be electrically isolated and locked out where possible.
[][]Ensure the control panel is switched off before carrying out any check.
[][]Maintenance activity must be carried out by trained technician/operators.
[][]“Under Maintenance” tag must be put while doing maintenance tasks.

System Description:

[][]Chiller is used to produce chilled water which is used in AHU’s cooling coil to cool the air. There are two chillers at the roof top area of Cephalosporin block and two at the roof top area of General Block. Each chiller has capacity of 250 Ton.
[][]The chiller works according to the Vapor Compression Refrigeration Cycle. There is an evaporator (heat exchanger) to chill the water by exchanging heat with the refrigerant. The refrigerant used in this system is R134a.

[][] The vapor refrigerant from the evaporator is sucked into the compressor and compressed to a higher pressure. There is a water cooled condenser to cool the refrigerant. The flow of refrigerant is controlled by using an expansion valve before entering into the evaporator.

Pre-Start Check:

[][]Check the power supply voltage within the utilization range.
[][]Verify that all refrigerant valves are “OPEN”.
[][]Check the chilled water.
[][]Check the Condenser water.
[][]Check cooling Tower water level.
[][]Check the fused-disconnect switch (es) that supplies power to the chilled water pump starter and the condenser water pump starter.
[][]Check all piping for leakage.
[][]Check the chilled water and condense water valve are “OPEN”.
[][]Visually inspect the chilled water pressure and condenser water pressure.
[][]Check the voltage of chiller.

Starting procedure:

[][]Following steps are followed to start the chillers
[][]Turn chiller circuit breaker (Panel Board) handle to “ON” Position.
[][]Start the chilled water pump
[][]Start Condenser water pump.
[][]Check the evaporator water flow.
[][]Check the condenser water flow.
[][]Start the cooling tower fan.
[][]After 10-30 Seconds Figure-I will be displayed.
[][]For checking condenser and evaporator circulating water we have to go to report option and check water flow.
[][]Touch the Report key and check water flow for condenser and chilled water circulating pump and oil temperature (Figure-II).
[][]After checking water flow, check the Setting of parameters.
[][]For setting parameter touch the” Setting” Key. Figure-III.
[][]Go back to Main screen menu and then touch the’ AUTO” key.
[][]After pressing the “AUTO” Figure-IV is displayed.

During Operation:

[][]Fill up the operational log book of chillers while the chillers are running on every 2 hours.

Stopping Procedure:

[][]At first Unlock the screen
[][]Touch the “STOP’’ key on screen.
[][]After stopping the chiller 5-10 minutes later
[][]Stop the condenser water pump.
[][]Stop chilled water circulating pump.
[][]Stop Cooling Tower Fan.

Chiller Preventive Maintenance Procedure:

[][]Use of a periodic maintenance program is important to ensure the best possible unit performance and efficiency.
[][]Fill up the maintenance log sheet of Chillers after doing maintenance.

Daily Maintenance

[][]Check the chiller’s evaporator and condenser pressures, and discharge oil pressure.
[][]Check the oil level in the chiller oil sump.
[][]Clean the chiller outside and surroundings.
[][]Check setting and operation of all controls and safety devices.

Weekly Maintenance

[][]Clean the environment of chiller room.
[][]Clean outside of the chillers, chilled water pumps.
[][]Clean outside of the condenser water pump.
[][]Check the electrical connection.

Monthly Maintenance

[][]Clean all water strainers in both the chilled and condensing water piping system.
[][]Measure the oil pressure drop. Replace oil filter if required.
[][]If operating conditions indicate a refrigerant shortage, leak checks the unit and confirm using soap bubbles.
[][]Repair all leaks.
[][]Check the motor bearing.
[][]Grease all pumps.

Annually Maintenance

[][]Check all isolators of pumps.
[][]Check starter contactors for wear and replace if required.
[][]Check motor winding insulation.
[][]Check motor amps draw.
[][]Clean condenser tubes.
[][]Check water pipeline for any leakage.
[][]Change the chilled water, refill with chemical.
[][]Change the condenser water.
[][]Check the evaporator and condenser flow switches.

Annexure

Annexure-I: Operational log sheet of Chillers
Annexure-II: Maintenance log sheet of Chillers

Chiller Operation and Maintenance Read More »

Operation & Maintenance of AHUS of Sterile Block

Operation & Maintenance of AHUS , Purpose

Operation & Maintenance of AHUS , The purpose of this SOP is to define the operation and maintenance procedure of Air Handling Units of Sterile Block of XX Pharmaceuticals Ltd.

Operation & Maintenance of AHUS , Scope

This SOP applies to all the AHUs which are located in the Sterile Block of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]AHU: Air Handling Unit (AHU)
[][]EHS: Environment, Health and Safety.
[][]PPE: Personal Protective Equipment.
[][]SOP: Standard Operating Procedure.

Responsibilities:

[][]The roles and responsibilities are as follows

Engineering (Validation) Department

[][]To prepare the SOP & revise it when necessary.

Engineering (Maintenance) Department

[][]To provide necessary support for smooth operation & maintenance of AHUs.
[][]To check the log books.

Operators/Technician

[][]To operate the AHUs according to the SOP.
[][]To do the maintenance job according to the schedule.
[][]To fill up the operation and maintenance log book.

Head of Engineering

[][]To approve any maintenance/plans activities related to the AHUs.

Head of Quality Assurance

[][]To approve this SOP.

Procedure

Precautions:

[][]All maintenance work must be carried out safely in accordance with the requirements of the Plant Safety Requirements and the EHS safety notices must be displayed around the plant. [][]Specific attention must be paid to the following:
[][]Personal protective equipment (PPE) such as masks, safety glass, boots etc. appropriate to the job must be worn.
[][]Equipment must be electrically isolated and locked out where possible.
[][]Ensure the control panel is switched off before carrying out any check.
[][]Maintenance activity must be carried out by trained technician/operators.

Filters:

[][]Filtration is ordinarily positioned first in the AHU to keep every one of the downstream parts clean. Contingent on the grade of filtration required, regularly channels will be organized in (at least two) progressive manages an account with a coarse-grade channel gave before a fine-grade channel, or other “last” filtration medium.

[][] The coarse-grade channel is less expensive to supplant and keep up with, and in this manner safeguards the more costly channels.

Heating and/or cooling coil:

[][]Air taking care of Unit needs to give warming, cooling, or both to change the stockpile air temperature, and dampness level contingent upon the area and the application.

[][] Chilled water from the chiller is gone through a twisting container of the cooling curl, heat trade among water and air. Blades are appended to the cylinders effectively increment the surface for heat move to water from air.

[][]Boiling water from the high temp water age framework is gone through a twisting container of the warming loop, heat trade between boiling water and air.

[][]Blades are appended to the cylinders increment surface for heat move to air.

Blower/Fan/Motor:

[][]In the air handling unit fan/motor is used for supplying or extracts air from room. Depending on the size of AHU more than one fan/motor is installed.

Dampers:

[][]In AHU dampers are provided to control the flow of conditioned air to the room.

Pre-Start Check

[][]Check that the electrical connection is supplied.
Ensure that the chilled water is supplied to the cooling coil.
[][]Ensure that the hot water is supplied to the heating coil.
[][]All maintenance panels are to be closed and check all maintenance panels and locks for perfect position.
[][]Make sure that filters have been installed properly in their places.
[][]Make sure all filters media are installed in correct airflow direction.
[][]Starting Procedure
[][]Power ON for VSD.
[][]Press “Hand” Button.
[][]Press Start Button.

During Operation

[][]Check that there is no unusual noise or vibration. Stop and investigate if found.
[][]The Operational Log Sheet (Annexure – I) of AHUs will be filled up once a week by the operator. The reading of magnehelic gauges will be used to monitor whether the filter is blocked.

[][] If the pressure reaches the maximum limit as stated in the filters will be changed or cleaned according to the described procedure in that SOP.

[][] Photocopy of all the approved forms will be used where easily applicable. For the cases where computer generated copies are relatively easy to handle, the exact format of the approved form can be used(except the approval sign) with the following notes as footer:
“This is a computer generated report. The format is as per the original approved form.”

Stopping Procedure

[][]Press the Stop (Red) button.(See Figure-I)
[][]Power off for VSD.

Preventive Maintenance

[][]At first switch off power supply /isolate the AHU from power supply. The maintenance job is performed by trained personnel. “Under Maintenance” be displayed in a prominent position on a machine
[][]undergoing maintenance work.

Fan/Motor

[][]Check for soiling, corrosion, damage and tendency of excessive vibration.
[][]Check the electrical connection.
[][]Check that all bolts, nuts and flexible connection are securely fixed.
[][]Check that vibration isolator mounts is functioning well.
[][]Inspect for any obstructions or blockages at air intakes and discharges.
[][]Check fan bearing are secured and no undue noise by observe/listen using metal bar as a conductor.
[][]Check noise or knocking from bearing, replace both bearings.
[][]Check fan bearing and lubricate with grease.
[][]Check whether the fan impeller rotates freely.

Drive Belt

[][]Belts that are split or have frayed edges or any other sign of damage must be replaced in full set.
[][]Check the belt tension and alignment, retention and realign if necessary.
[][]Check drive belt, if damage replace belt.

Coil Section

[][]Ensure that coils are cleaned.
[][]Check for any leakage in coil.
[][]Ensure coil fins are not damage when performing dry/wet cleaning.

[][]Check that drain pan and drain trap are free from blockage and water accumulation at pan.

Filter Section:

[][]Disposable filters must be replaced each time when pressure drop reaches the indicated by dirty condition by magnehelic gauges. Washable filters must be cleaned periodically. For filters changing and cleaning procedure follow the SOP..

Dampers:

[][]Check for dirt accumulation, damage, and sign of corrosion.
[][]Clean with cloth or high pressure air.
[][]Check damper blade by turning manually or central control for smooth operation.

Preventive Maintenance Schedule

[][]During maintenance work the equipment must be electrically isolated. After performing maintenance works maintenance log book (as same as Annexure – II) has to be filled up by the operator.

Weekly Maintenance

[][]Check and clean fan
[][]Check Fan for excessive vibration.
[][]Check Fan belt.
[][]Check fan motor bearing.
[][]Check the functioning of auto actuator valves of chilled and hot water line.

Monthly Maintenance

[][]Check and Clean Motor.
[][]Check the belt drive tension.
[][]Check or replace V-belt condition.
[][]Check filter.
[][]Check nuts and bolts and tighten it if necessary.
[][]Grease the motor if necessary.

Quarter yearly Maintenance

[][]Check Vibrator Isolator.
[][]Check the electrical connection.
[][]Check the bearing for motor.
[][]Check drain trap clog.

Half Yearly Maintenance

[][]Check fan bearing.
[][]Check motor bearing.
[][]Check bolt and nut tighten.
[][]Check fin block.
[][]Check coil leakage.
[][]Check dirt accumulation of damper & Heater.
[][]Check sign of damage.
[][]Check position of damper.

Yearly Maintenance

[][]Servicing cooling coil and heating coil.
[][]Check/treat/repair corrosion of coil.
[][]Check/repair Electrical control box.
[][]Check/Replace Circuit Breaker.
[][]Check/replace internal lighting.

Annexure

Annexure-I: Differential Pressure Monitoring Log sheet of AHUs
Annexure-II: Maintenance Log Book of AHUs

Operation & Maintenance of AHUS of Sterile Block Read More »

HEPA Filter Cleaning & Changing Procedure

HEPA Filter Cleaning , Purpose:

HEPA Filter Cleaning , The purpose of this SOP is to define the cleaning and changing procedure of G4, F7, F9 and HEPA filters of HVAC system of XX Pharmaceuticals Ltd.

HEPA Filter Cleaning , Scope:

This Standard Operating Procedure applies to the G4, F7, F9 and HEPA filters of HVAC system installed at Sterile and Solid Block of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure
[][]AHU: Air Handling Unit
[][]G4 Filter: G4 filters are used as pre filters inside the AHUs and in low return line of rooms of HVAC system. This is also known as coarse graded filter
[][]F7 and F9 Filter: F7 and F9 filters are used as intermediate filters inside the AHUs of HVAC system. These are factory fabricated and mounted with galvanized steel or plastic frames
[][]HEPA: High Efficiency Particulate Air
[][]DOP: Di – Octyl Phthalate
[][]PAO: Poly Alpha Olefin

Responsibilities:

[][]The roles and responsibilities are as follows:

Engineering (Validation) Department

[][]Preparing the SOP and revise it when necessary.

Engineering (Maintenance) Department

[][]To provide necessary support for performing cleaning/changing operation smoothly.
[][]To ensure that the operators are responsible to carry out the operation and fill up the logbooks.

Operators/Technician

[][]To clean/change the filters according to the SOP.
[][]To fill up the log sheets.

Manager, Engineering

[][]To ensure that the cleaning/changing of filters are done properly.

Manager, Quality Assurance

[][]To approve the SOP.
[][]To ensure overall implementation of this SOP.

Procedure:

Precautions:

[][]All operation work must be done safely in accordance with the requirements of the Plant Safety Statement and the safety notices around the plant. Specific attention must be paid to the following:
[][]Do not open the doors of AHU while the motor is running.
[][]Do not wash the filters beside the AHUs.
[][]Use personal protective equipment and clothing as necessary at the time of performing cleaning/changing work.
[][]Be careful about the hot water line.

System Description

[][]In HVAC system, the filtration of air is done in three stages to remove the particulates from the air. The stages are: primary, secondary and tertiary stages.

Primary stage:

[][]Coarse graded filters are used in primary stage. The grade of this filter is G4. This type of filter is washable. This is also used in the low return duct line of AHUs. This type of filters are used to remove the coarse particles.

Secondary stage:

[][]After primary stage filtration the air is filtered in secondary stage filter inside the AHUs. Normally, the secondary stage filters are of F7/F9 graded. The bag type F7 filter is washable but cartridge and flat type F7 and F9 filters are not washable. They have to be replaced after being blocked with particles.

Tertiary stage:

[][]The air is finally filtered by the HEPA filters in tertiary stage. In some cases, filtration is done by the HEPA filters after secondary stage inside the AHU followed by terminal HEPA filter. Otherwise, HEPA filter is used only in the terminal of supply duct. These filters are neither washable nor cleanable rather than these are replaced or changed in case they fail the filter integrity test commonly known as DOP/PAO test.
[][]Monitor the differential pressure in the magnehelic gauge across the filters of AHUs in the log sheet.  If the differential pressure is beyond the set limit, then clean/change the filters.

Cleaning Procedure

[][]Cleaning of G4 and F7 (bag type) filters:
[][]Switch off the power of AHU and wait until the motor rotation is fully off.
[][]Open the door of the filter section and unmount the filter from its frame.
[][]Take the filter to the wash area at the roof top of both cephalosporin and general blocks.
[][]Wash the filter with water. Then, use any kind of non ionic cleaning agent to clean the filter.
[][]After cleaning the filters are dried.
[][]During cleaning a lot of dust may come out from the filters. So, use mask, goggles, hand gloves and other clothes to be safe from any harmful dust.
[][]After drying set the filters in the filter frame.
[][]The G4 filters of low return and inside the AHUs are cleaned once a week and every 15 days respectively for periodic maintenance. The F7 (bag type) filters are cleaned once a month.
[][]Fill up the log sheet (Annexure – I) after performing the activities.

Changing Procedure

[][]Changing of G4, F7, F9 filters:
[][]Both the G4 and F7 (bag type) filters are changed when filters cannot filter the air although it has been cleaned.
[][]Monitor the differential pressure across the filters. If the differential pressure across F7 (cartridge and flat type) and F9 filters is more than 500 Pa, the filters have to be changed. Both of these filters are changed once in a year for periodic maintenance.
[][]To change the filters follow the steps 1 to 2 of previous section.
[][]Take the filters to the dispose area.
[][]Destroy the filters in the dispose area abiding by the proper safety rules.
[][]Set a new filter.
[][]Fill up the log sheet (Annexure – II).

Changing the HEPA filters:

[][]The differential pressure across the HEPA filters (fitted inside the AHUs) is monitored. These filters are changed when the differential pressure exceeds 300 Pa.
[][]The integrity test (DOP/PAO) is performed at a defined interval for every HEPA filters. The filter is changed if it fails the test.
[][]To change the HEPA filters follow the previous steps
[][]After replacing the filter fill up the log sheet (Annexure – II).

Annexure:

Annexure – I: Log sheet for cleaning of G4 & F7 (bag type) filters.
Annexure – II: Log sheet for changing of G4, F7, F9 and HEPA filters.

HEPA Filter Cleaning & Changing Procedure Read More »

Pure Steam Generation System Operation

Pure Steam, Purpose:

Pure Steam, The purpose of this SOP is to define the Operation of Pure Steam Generation System manufactured by Watertown in order to ensure its smooth & trouble-free operation and generation of qualified pure steam.

Pure Steam, Scope:

This Standard Operating Procedure applies to the pure steam generation system manufactured by Watertown, which is located at the Utility area (roof top) of Sterile block of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]PW: Purified Water.
[][]HMI: Human Machine Interface.
[][]PS: Pure steam.

Responsibilities:

[][]The roles and responsibilities are as follows:

Engineering (Validation) Department

[][]Preparing the SOP and revise it when necessary.

Engineering (Maintenance) Department

[][]To provide necessary support for smooth operation of the system.
[][]To ensure that the operators are responsible to carry out the operation and fill up the logbooks.

Operators

[][]To operate the system according to the SOP.
[][]To fill up the logbook.

Head of Engineering

[][]To ensure that the operation of PW plant are done properly.

Head of Quality Assurance

[][]To approve the SOP.
[][]To ensure overall implementation of this SOP.

Procedure:

Precautions:

[][]All operation work must be done safely in accordance with the requirements of the Plant Safety Statement and the safety notices around the plant. Specific attention must be paid to the following:
[][]The tank walls are hot. The water in the tank is at 80°C when the unit is operating. Contact with 80°C water will cause burning.
[][]Use Personal Protective Equipment during handling of any kind of chemical.
[][]Be careful about the hot water and steam line.
[][]Ensure all the utilities before doing any operation.

System Description:

[][]Pure steam is generated by heating the purified water. In this plant it is generated during the production of Water For Injection.
[][]So, the main control panel for WFI Generation system and PS is same. Purified water is converted to pure steam by exchanging the heat with the industrial steam in the heat exchanger.
[][]Then, the pure steam is supplied to the user point by opening the pneumatic valve PBV501. The capacity of steam generation is 250 Kg/hr.

Operating Procedure:

Starting of Pure steam generation:

[][]Switch on the main breaker to supply electrical power of the plant.
[][]Open the industrial steam inlet valve such that the pressure is within 3-4 bar.
[][]Ensure compressed air and other utilities to run the plant.
[][]Switch ON the UPS. In case of emergency stop, release the emergency stop switch.
[][]Then starting page will appear and press on HMI.
[][]Press Start on that screen
[][]Press User key. After that following screen will appear
[][]Press the “Parameter setting**” button to set the parameters. Following screen will appear:
[][]Give user ID and Password and press OK.
[][]Then the parameter setting screen will appear.
[][]Press on any reading (yellow marked) to change the value if required.
[][]Then press flow chart status on Figure V.
[][]Screen of WFI/PS generation flow chart will appear.
[][]Press the Auto On button to operate the plant automatically.

[][]Open the pneumatic valve PBV501 when the temperature of pure steam reaches the required temperature limit.

During operation:

[][]Check PS temperature.
[][]Check Pure Steam pressure.
[][]Check that there is no unusual noise or vibration. Stop and investigate if it is found.
[][]The Operational Log Sheet (Annexure – I) of PS generation will be filled up by the operator on hourly basis.

Stopping procedure:

[][]Close the PS valve (PBV501).
[][]Press the Auto Off to stop the plant.
[][]Then switch the power off by turning the circuit breaker to off position.
[][]Close the industrial steam inlet valve.

Annexure:

Annexure – I: Operational Log Sheet of pure steam generation system.

Pure Steam Generation System Operation Read More »

Boiler Operation and Maintenance

Boiler, Purpose:

Boiler, The purpose of this SOP is to define the standard operation and maintenance procedure of Boiler in order to ensure its smooth & trouble-free operation and generation of steam.

Boiler, Scope:

This SOP is applicable to Cochran Diesel / Gas Boiler which is located at the ground floor of Sterile Block of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]Boiler: A boiler is a closed vessel in which water is heated; steam is generated and superheated from any combination of heat from combustible fuels or electricity.
[][]EHS: Environment Health and Safety.
[][]PPE: Personal Protective Equipment.
[][]SOP: Standard Operating Procedure.
[][]TDS: Total Dissolved Solids.

Responsibilities:

[][]The roles and responsibilities are as follows:

Validation (Engineering) Department

[][]Preparing the SOP and revise it when necessary.

Engineering Department

[][]To provide necessary support for smooth operation & maintenance of boiler.
[][]To ensure that the operators are responsible to carry out the operation and maintenance work and regular checking of critical components and logbooks.
[][]To develop a list of spare parts based on the manufacturer’s recommendations and to forward the list to the Planning and Procurement department with a request to place order as required.

Operators

[][]To operate the Boiler according to the SOP.
[][]To fill up the logbooks related to the Boiler.
[][]To do the maintenance according to the check list.

Manager, Engineering

[][]To ensure that the operation and maintenance of the Boiler.
[][]To approve any maintenance/plans related to the Boiler.

Manager, Quality Assurance

[][]To ensure overall implementation of this SOP.

Procedure:

Precautions:

[][]All operation and maintenance work must be done safely in accordance with the requirements of the Plant Safety Statement and the safety notices around the plant. Specific attention must be paid to the following:
[][]Personal protective equipment (PPE) and clothing appropriate to the job must be worn.
[][]Ensure the control panel is switched off before carrying out any maintenance.
[][]Maintenance activity must be carried out by trained technician/operators.
[][]No unauthorized person is allowed to do any kind of operation or maintenance to the boiler.
[][]The cover doors must be kept closed during operation.
[][]The safety mechanism of the machine must be checked by the operator for reliability in each and every working day.
[][]“Under Maintenance” be displayed in a prominent position on a machine, equipment or facility undergoing maintenance work.

Pre-start Check

[][]To ensure the permanent ventilation of the boiler house (Excluding doors and windows) is capable of supplying sufficient air for combustion and to keep the boiler house cool.
[][]Check all mechanical connections are properly tightened and have not worked loose in transit.
[][]Check direction of rotation of burner fan motor.
[][]To ensure oil / Gas is present.
[][]To ensure fuel / Gas valve is “OPEN”.
[][]To ensure water level in the feed water tank is enough.
[][]To ensure the burner switch on the control panel is OFF.
[][]To ensure feed water pump valve is “OPEN”
[][]To ensure that the fuel / Gas selector switch has selected OIL.
[][]To ensure that the gas isolating valves are closed and the oil isolating valves are open.
[][]The boiler feed pump should be filled with water on its suction side.
[][]The boiler should be filled with softened water.
[][]Ensure the fuel / Gas filters are clean.

Starting Procedure

[][]Main switch turn to “ON” position.
[][]Switch on the feed water pump selector switch (No.1 or No.2 for respective pump selection).
[][]Turn feed water pump control switch to “AUTO” position from “OFF” position.
[][]Turn burner control switch to “LOW” position from “OFF” position.
[][]When boiler steam pressure reaches up to (6.5-7) bar then turn burner control switch to “LOW” position from “OFF” position.

During Operation

[][]All boiler gaskets, valve stuffing boxes and valve gaskets are to be checked periodically during the boiler heat-up.
[][]The boiler pressure gauge should be observed during this heat-up period.
[][]Water analysis after every 12 hours of operation. If feed water is found to be hard any time, stop the boiler immediately. Drain the water from the service tank.
[][]Regenerate the softener and fill up the feed water tank then restart the boiler.
[][]Any excessive sound coming from motors or any moving part.
[][]All valves, joints, head-hole and manhole covers are leak tight.
[][]The water level is correct and steady.
[][]Steady steam pressure is maintained.
[][]Check Safety valve.
[][]Check fuel pressure.
[][] The Operational Log Sheet (Annexure – I) of boiler will be filled up on every hour by the operator. Photocopy of all the approved forms will be used where easily applicable. For the cases where computer generated copies are relatively easy to handle, the exact format of the approved form can be used(except the approval sign) with the following notes as footer:

“This is a computer generated report. The format is as per the original approved form.”

Boiler Stopping Procedure

[][]Turn burner control switch to “OFF” position.
[][]Turn feed water pump control switch to “OFF” position.
[][]Fuel / Gas valve is off.
[][]In case of an emergency where immediate shutdown is necessary, the emergency stop push button should be pushed immediately.

Preventive Maintenance Planning

[][]During maintenance works the equipment must be electrically isolated. After performing maintenance works maintenance log book (as same as Annexure – II) has to be filled up by the operator. The schedule which follows must be applied at the Interval which occurs first.

Daily Maintenance

[][]Ensure that the fuel filters are clean.
[][]Check the water level.
[][]Clean the viewing glass
[][]Check the operating pressures.
[][]The boiler feed pump should be filled with water on its suction side.
[][]The boiler should be filled with softened water.
[][]Check the quality of feed water.
[][]Check the safety valve.

Weekly Maintenance

[][]Clean the flame sensor & viewing glasses.
[][]Check the water level is properly controlled.
[][]Check the low level & extra low level alarms by reducing the water level.

Monthly Maintenance

[][]Clean igniter assembly.
[][]Drain the feed water tank to remove the sediment.
[][]Clean the burner nozzle & ignition electrodes.
[][]Check oil / Gas leaks.

Quarterly Maintenance

[][]Clean electrical contacts of all relays & tighten loose connection if any.
[][]Check the water pump seal non-return valve.
[][]Check & clean the furnace if required.
[][]Service burner unit.
[][]Check door and furnace seals.
[][]Visual check of refractory’s.
[][]Check control panel.
[][]Set-up combustion.
[][]Check safety interlocks.
[][]Drain & clean the water service tank.
[][]Check the feed water pump.
[][]Check the seals of the feed water pump.
[][]Clean the blower fan blades

Half Yearly Maintenance

[][]Check the valves for leakages; lap them if found leakage.
[][]Lubricate the bearing of water pump.
[][]Check the sealing of Manhole, head holes & clean out door of smoke box.

Annually Maintenance

[][]Check the burner position, adjust if required.
[][]Clean the boiler tubes with brush.
[][]Clean the combustion chamber.
[][]Overhaul the valves.
[][]Check the door refractory for any damage, repair if necessary.
[][]Check the door seal to make sure that there is no gas leakage.
[][]Clean the water side of the boiler thoroughly.

Annexure:

Annexure – I: Operational Log sheet of Boiler.
Annexure – II: Maintenance Log sheet of Boiler.

Boiler Operation and Maintenance Read More »

Dehumidifier Operation and Maintenance

Dehumidifier Operation and Maintenance, Purpose:

Dehumidifier Operation and Maintenance, The purpose of this SOP is to define the operation and maintenance procedure of dehumidifiers of HVAC systems of Sterile and Solid of XX Pharmaceuticals Ltd.

Dehumidifier Operation and Maintenance, Scope:

This Standard Operating Procedure applies to the dehumidifiers of HVAC system installed at Sterile and Solid Block of XX  Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]AHU: Air Handling Unit.

[][]Dehumidifier: A dehumidifier is an equipment of HVAC system which reduces the level of humidity in the air. This basic dehumidification process uses a special humidity absorbing material called a desiccant, which is exposed to the air to be conditioned.

Responsibilities:

[][]The roles and responsibilities are as follows:

Engineering (Validation) Department

[][]Preparing the SOP and revise it when necessary.

Engineering (Maintenance) Department

[][]To provide necessary support for smooth operation of the system.
[][]To ensure that the operators are responsible to carry out the operation and fill up the logbooks.

Operator

[][]To operate the system according to the SOP.
[][]To fill up the log sheets.

GM, Engineering

[][]To ensure that the system is operated properly.

Procedure:

Precautions:

[][]All operation work must be done safely in accordance with the requirements of the Plant Safety Statement and the safety notices around the plant. Specific attention must be paid to the following:
[][]Do not touch the steam line with bare hands.
[][]Perform any kind of maintenance after switching off electrical power and also after cooling of hot pipe line.
[][]Use personal protective equipment and clothing as necessary at the time of performing maintenance work.
[][]Put the “UNDER MAINTENANCE” tag on an easily visible place of the equipment before performing maintenance.

System Description

[][]In an HVAC system a dehumidifier is used to reduce the humidity of air. There are various ways to dehumidify the air. Desiccant type dehumidifier is commonly used in HVAC system of pharmaceutical industry.
[][]A chemical (normally silica gel) is used as a desiccant which adsorbs the moisture in the air. The air to be conditioned is passed through the bed of silica gel which adsorbs the moisture.
[][]This silica gel is again regenerated using the heated air. The heated air is produced by using steam in the heat exchanger or by electrical heater.

Pre-start check

[][]Check that the related AHU of the dehumidifier is switched on.
[][]The steam pressure in the steam header should be between 2 to 4 bar.

Starting Procedure

[][]Switch on the main circuit breaker.
[][]Check the power indicating light.
[][]Turn the selector switch to “MANUAL” mode to run the dehumidifier using manual mode. “AUTO” position is selected to run the dehumidifier in automatic mode.

During Operation

[][]During operation, the indicating light “OPERATION” becomes on.
[][]Check the rotational direction of motor and bed of silica gel. It should be in clockwise direction.
[][]Check if there is any alarm in the alarm indicator and resolve it.

Stopping Procedure

[][]Turn the selector switch to off (O) position to switch off the dehumidifier.
[][]Switch off the main circuit breaker.

Preventive Maintenance of Dehumidifier

[][]Perform any kind of maintenance after switching off the electrical power and cooling of electrical heater.
[][]Fill up the log book after performing preventive maintenance (according to Annexure – I and Annexure – II).
[][]Perform preventive maintenance according to the following schedule:

Monthly

[][]Check the filters and clean if necessary.

Half yearly

[][]Check the rotor drive and clean with compressed air if it is necessary.
[][]Check that the rotor sealing is in the right position and not damaged.

Yearly

[][]Check the rotor bearing.
[][]Check the rotor surface.
[][]Check the motors for any abnormal sound.

After 3 years

[][]Change the silica gel.

Annexure:

Annexure – I: Log sheet for preventive maintenance of Dehumidifier

Dehumidifier Operation and Maintenance Read More »

Chilled Water Circulating Pumps Operation

Chilled Water Circulating Pumps , Purpose:

Chilled Water Circulating Pumps , The purpose of this SOP is to define the operating procedure of chilled water and cooling water circulating pumps of HVAC system of XX Pharmaceuticals Ltd.

Chilled Water Circulating Pumps , Scope:

This Standard Operating Procedure applies to the chilled and cooling water circulating pumps installed at the roof top area of Sterile Block of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:
VSD: Variable Speed Driver.

Responsibilities:

[][]The roles and responsibilities are as follows:

Engineering (Validation) Department

[][]Preparing the SOP and revise it when necessary.
[][]Engineering (Maintenance) Department
[][]To provide necessary support for smooth operation of the system.

Operator

[][]To operate the system according to the SOP.

Manager, Engineering

[][]To ensure that the system is operated properly.

Manager, Quality Assurance

[][]To approve the SOP.
[][]To ensure overall implementation of this SOP.

Annexure:

N/A

Procedure:

Precautions:

[][]All operation work must be done safely in accordance with the requirements of the Plant Safety Statement and the safety notices around the plant.
[][]In HVAC system, chilled water is used to cool the air inside the AHUs. This chilled water is produced in chiller and circulated from chiller to heat exchanger of AHUs through pumps. This acts as a closed loop.
[][]In cooling tower, the cooling water is circulated from cooling tower to the condenser of chiller through pumps.

Pre-start check

[][]Ensure that pipeline is filled with water. If there is not sufficient water, the pump may be damaged.

Starting Procedure

For VSD
[][]Switch on main circuit breaker to give electrical power to VSD.
[][]Press the  “HAND” button and then press the Green button on VSD to start the pumps.

[][]Press the green button to start the pump. During operation check for any alarm (RED indicating light)
#Stopping Procedure
#For VSD
[][]Switch off the pump by pressing the red button on VSD.
[][]Switch off the main circuit breaker.
[][]For Star Delta connection
[][]Press the RED button to switch OFF the pump.
[][]Switch off the main circuit breaker.

Chilled Water Circulating Pumps Operation Read More »

Cooling Tower Operation and Maintenance

Cooling Tower , Purpose

Cooling Tower , The purpose of this SOP is to define the operation and maintenance procedure of Cooling Towers of XX Pharmaceuticals Ltd.

Cooling Tower , Scope

This SOP applies to the cooling towers, installed at the roof top area of Solid and Sterile Blocks of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]EHS: Environment Health and Safety.
[][]PPE: Personal Protective Equipment.
[][]SOP: Standard Operating Procedure.

Responsibilities:

[][]The roles and responsibilities are as follows:

Engineering (Validation) Department

[][]To prepare the SOP & revise it when necessary.

Engineering (Maintenance) Department

[][]To provide necessary support for smooth operation & maintenance of cooling towers.
[][]To ensure that the operators are responsible to carry out the operation and maintenance work and regular checking of the critical components and logbooks.
[][]To develop a list of spare parts based on the manufacturer’s recommendations and to forward the list to the Planning and Procurement department with a request to place order as required.
[][]To engage technician/mechanic/operator/supplier in repair and maintenance work.

Operators/Technician

[][]To operate the cooling tower according to the SOP.
[][]To do the maintenance job according to the schedule.

Head of Engineering

[][]To ensure that the operation and maintenance of cooling towers are done properly.
[][]To approve any maintenance plans related to the cooling towers.

Head of Quality Assurance

[][]To approve this SOP
[][]To ensure overall implementation of this SOP.

Procedure

Precautions:

[][]All maintenance work must be carried out safely in accordance with the requirements of the Plant Safety Requirements and the EHS safety notices must be displayed around the plant.

Specific attention must be paid to the following:

[][]Personal protective equipment (PPE) and clothing appropriate to the job must be worn.
[][]Equipment must be electrically isolated and locked out where possible.
[][]Ensure the control panel is switched off before carrying out any check.
[][]Maintenance activity must be carried out by trained technician/operators.
[][]“Under Maintenance” tag be displayed in a prominent position on a machine, equipment or facility undergoing maintenance work.

Pre-Start Check

[][]Inspect all wiring connections to be sure they are clean and tight.
[][]Check the power supply voltage within the utilization range.
[][]Check cooling Tower basin water level.
[][]Check the fused-disconnect switch(es) that supplies power to the condenser water pump starter.
[][]Start Condenser water pump.
[][]Start the cooling tower fan.
[][]Check all piping for leakage.
[][]Check the condense water valve are “OPEN”.
[][]Visually inspect the condenser water pressure.
[][]Check condense water modulating butterfly valve position.
[][]Check the condense water line make-up water tank water level.

[][]Starting procedure
[][]Power ON for VSD.
[][]Press “Hand” Button.
[][]Press Start Button.

Stopping Procedure

[][]Press the Stop (Red) button.(See Figure-I)
[][]Power off for VSD.

Preventive Maintenance schedule

[][]Use of a periodic maintenance program is important to ensure the best possible unit performance and efficiency. Fill up the Annexure – I and II after completing the maintenance tasks accordingly.

Daily Maintenance

[][]Check the condense water pressure,
[][]Check cooling towers basin water level.
[][]Clean the cooling towers outside and surroundings.

Weekly Maintenance

[][]Current drawn by the fan motor.
[][]Check cooling tower fan rotation.
[][]Unusual noise, vibration, and so forth.

Monthly Maintenance

[][]Check and clean strainer.
[][]Clean Fan blade.
[][]Check the Belt tension.
[][]Clean the Internal side of the cooling Tower.
[][]Check and adjust sump water level.
[][]Check and adjust blow-down.
[][]Inspect water distribution.
[][]Clean the cooling towers Fins.
[][]Change the cooling water, refill with chemical.
[][]Grease the cooling tower motor.
[][]Clean the Y-strainer of chilled water and condenser water line.

Annually Maintenance

[][]Check/clean all parts of cooling tower.
[][]Clean cooling tower basin.
[][]Clean cooling tower fins.
[][]Check setting and operation of all controls and safety devices.
[][]Check starter contactors for wear and replace if required.
[][]Check motor winding insulation.
[][]Check motor amps draw.
[][]Check and adjust the water flow.
[][]Change the water of chilled water line.

Annexure

Annexure-I: Maintenance Log sheet of Cooling Tower

Cooling Tower Operation and Maintenance Read More »

HVAC System Filters Numbering

HVAC System Filters Numbering, Purpose:

HVAC System Filters Numbering, The purpose of this SOP is to define the procedure for the establishment of identification number of terminals/filters of HVAC system of XX Pharmaceuticals Limited.

HVAC System Filters Numbering, Scope:

All types of filters, diffusers and return risers/grilles of HVAC system of both Solid and Sterile Blocks are covered by this SOP.

Definitions / Abbreviation:

[][]HVAC: Heating Ventilation and Air Conditioning.
[][]HEPA: High Efficiency Particulate Air.
[][]AHU: Air Handling Unit.

Responsibilities:

[][]The roles and responsibility are as follows:

Engineering Person(related to HVAC)

[][]To fill up the request form (Annexure – 1) to get the ID of newly fitted filters/diffusers/return grilles.
[][]To inform validation (engineering) department if there is any replacement of terminals/filters.

Engineering (Validation) Department

[][]To give the ID of filters/diffusers/return grilles.
[][]To maintain a register for terminals/filters of HVAC system.

Functional Head

[][]To ensure that all the terminals/filters of HVAC system are numbered according to this SOP and any inclusion or exclusion is reported to the Validation (Engineering) department.

Head of Quality Assurance

[][]To ensure overall implementation of this SOP.

Procedure:

[][]Supply Diffuser and Filter Numbering
[][]Filters will be numbered using the following convention:
[][]AAAA – BBBB – CCC – XXX
Where,
[][]AAAA/AAA/AA: 4/3/2 characters to indicate the area of the plant.
[][]BBB/BB/B: 3/2/1 characters to indicate the diffuser and filter.
[][]For a diffuser and filter combination the code will be ‘DF’. If there is a swirl diffuser and filter, the character will be ‘SDF’.
[][]For a supply terminal without filter, the code will be only ‘D’ for diffuser. Only ‘F’ is used for the filters inside the AHUs.
[][]CCCC/CCC: 4/3 characters to indicate the grade and type of filter.
[][] First 2/3 characters indicate the grade of filters and last character indicates the type of filter (bag type, flat type etc.).
[][]The character will be 000 in case of having no filter with the supply diffuser.
[][]XXX: Three digits numerical code to indicate the sequential number of the same type of filter in an area.
For an example, a terminal flat type HEPA filter of grade H13 of Production Area of Sterile Block will be numbered according to the following way:

SPRD – DF – H13F – 001

001=Sequential Number for that area

H13F=H13 Grade and Flat type filter.

DF =Diffuser and Filter

SPRD=Sterile Production Area

Return Grille/Riser, Filter and Exhaust Grille Numbering

[][]All diffusers and return grilles of HVAC system of the plant will be numbered using the following convention:
AAAA – BBB – CCC – XXX
Where,
AAAA/AAA/AA: 4/3/2 characters to indicate the area of the plant.
[][]BBB: 3 characters of which first 2 characters indicate either low return riser or high return.

[][]Last character indicates filter or grille. ‘RR’ or ‘HR’ is used to indicate the low return riser and ceiling return respectively. ‘

[][]F’ and ‘G’ is be used for last character to indicate the filter and grille correspondingly. For exhaust grille the code will be 2 letters ‘EG’.
[][]CCC: 3 characters to indicate the filter grade and type of filter.

[][]If there is no filter in the return, the character will be 000.
[][]XXX: Three digits numerical code to indicate the sequential number of the same type of terminals/filters of a particular area.
[][]For an example, a low return riser of production area of general block with a G4 bag type filter is identified according to the following way:

PRD – RRF – G4B – 001

001=Sequential Number.

G4B=Filter grade and type

RRF =Low return riser with filter

PRD=Solid Block Production Area

[][]All terminals/filters of HVAC system will be tagged containing ID number. Format of filter identification tag is as follows:

[][]ID Number##

[][]The length and height of the box is 4.0 inch and 0.4 inch respectively. Arial font of size 10 shall be used for all the letters.
[][]A register of Terminal/Filter ID will be reserved in the validation (Engineering) department. (See Annexure – III).

[][]To get the ID of newly installed filters/terminals, the request form for ID (Annexure – II) will be filled up by the respective engineers and sent to the validation (engineering) department. Validation department will provide the sticker of ID and photocopy of the request form after giving new ID.
[][]If a Terminal/Filter is replaced with a new one, the new ID no. will be provided and the previous ID no. will not be used again.
[][]If any filter of new grade (which is not listed in the Annexure – I) is installed, the new filter will be added in the Annexure – I by handwriting of Head of QA with signature and date without reviewing the whole SOP. The Annexure – I will be added on the next version of this SOP.
[][]Photocopy of all the approved forms will be used where easily applicable. For the cases where computer generated copies are relatively easier to handle, the exact format of the approved form can be used (except the approval sign) with the following notes as footer:

[][]“This is a computer generated report. The format is as per the original approved form”

Annexure:

Annexure-I : Code for Grade and Type of Filters.
Annexure-II : Request Form for ID Number of New Terminal/Filter of HVAC system.
Annexure-III : Register of Terminal/Filter of HVAC system.

HVAC System Filters Numbering Read More »

Purified Water System Sanitization Procedure

Purified Water System Sanitization, Purpose:

Purified Water System Sanitization , The purpose of this SOP is to define the sanitization procedure of purified water distribution system in automatic mode.

Scope:

Purified Water System Sanitization , This Standard Operating Procedure applies to the PW Distribution systems manufactured by Watertown, which is located at the Utility area (roof top) of both Solid and Sterile Blocks of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]PW: Purified Water.
[][]HMI: Human Machine Interface.
[][]PQ: Performance Qualification.

Responsibilities:

[][]The roles and responsibilities are as follows:

Engineering (Validation) Department

[][]Preparing the SOP and revise it when necessary.

Engineering (Maintenance) Department

[][]To provide necessary support for smooth operation of the system.
[][]To ensure that the operators are responsible to carry out the operation and fill up the logbooks.
[][]To inform PW user departments not to open the valves during sanitization.

Operators

[][]To operate the system according to the SOP.
[][]To fill up the logbooks.

Head of Engineering

[][]To ensure that the operation of PW plant are done properly.

Head of Quality Assurance

[][]To approve the SOP.
[][]To ensure overall implementation of this SOP.

Procedure:

Precautions:

[][]All operational work must be done safely in accordance with the requirements of the Plant Safety Statement and the safety notices around the plant. Specific attention must be paid to the following:

[][]Be careful about the hot water and steam line.
[][]Ensure all the utilities before doing any operation.
[][]Do not touch the steam and hot water line with bare hands.
[][]Do not open any valve of distribution line during sanitization.
[][]Ensure at least 40% water level in the PW storage tank before starting sanitization.

System Description:

[][]There are two distribution systems of purified water in cephalosporin and general block. There is a shell and tube type heat exchanger in distribution loop to sanitize the system.
[][]During sanitization, purified water is heated using industrial steam at a temperature of 80–90⁰C. Then, this hot water is circulated through distribution loop for a period of 60 minutes.
[][]Cooling is done after sanitization at a temperature of 40⁰C using chilled water.

Sanitization Procedure:

Prestart check:

[][]Ensure minimum 3 bar industrial steam pressure before starting sanitization.
[][]Chilled water temperature has to be less than 10⁰C.
[][]Close all the valves of distribution line and inform all the PW user departments not to open the valve during sanitization period
[][]Check the water level in the PW storage tank. It has to be minimum 40%.

Starting of Sanitization system in automatic mode:

[][]Switch on the main breaker to supply electrical power of the plant.
[][]Ensure compressed air and other utilities to run the plant.
[][]Switch ON the UPS. In case of emergency stop, release the emergency stop switch.
[][]Switch ON the UPS. In case of emergency stop, release the emergency stop switch.
[][]Then starting page will appear and press on HMI.
[][]Then the following screen will appear. Press “Control flow”.

[][]Press the “Sanitization OFF” and give user ID and password.

[][]Press the “Sanitization OFF” again to start the system in automatic mode.

During Sanitization:

[][]During sanitization PW is circulated through the distribution line at a temperature of 80–90⁰C. After cooling the sanitization will be automatically stopped when the water temperature decreases to 40⁰C.
[][]Fill up the log sheet (Annexure – I) at 30 minutes interval after starting the cycle of sanitization.

Sanitization Frequency:

[][]After successful completion of chemical and microbiological tests of PQ (phase-1, phase-2 and phase-3 study) of PW system, the sanitization frequency has been finalized to 14 days interval.
[][]If the plant remains closed for any long vacation, then the distribution system will be sanitized.
[][]The distribution loop of General Block will either be sanitized prior to cephalosporin block’s loop or will be sanitized both at a time.

Annexure:

Annexure – I: Operational Log Sheet of Sanitization of PW distribution system

Purified Water System Sanitization Procedure Read More »

Hot Water System Operation And Maintenance

Hot Water System, Purpose:

Hot Water System, The purpose of this SOP is to define the operation and maintenance procedure of Hot Water System of XX Pharmaceuticals Ltd.

Hot Water System, Scope:

This Standard Operating Procedure applies to the Hot Water System installed at the roof top of of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]AHU: Air Handling Unit.
[][]Hot Water System: In HVAC system hot water system is used to produce hot water which is used in AHU’s hot water coil to reduce the relative humidity of air.
[][]H.W: Hot Water.
[][]PRV: Pressure Regulating Valve.

Responsibilities:

[][]The roles and responsibilities are as follows:

Engineering (Validation) Department

[][]Preparing the SOP and revise it when necessary.

Engineering (Maintenance) Department

[][]To provide necessary support for smooth operation of the system.
[][]To ensure that the operators are responsible to carry out the operation and fill up the logbooks.

Operator

[][]To operate the system according to the SOP.
[][]To fill up the log sheets.

Manager, Engineering

[][]To ensure that the system is operated properly.

Manager, Quality Assurance

[][]To approve the SOP.
[][]To ensure overall implementation of this SOP.

Procedure:

Precautions:

[][]All operation work must be done safely in accordance with the requirements of the Plant Safety Statement and the safety notices around the plant. Specific attention must be paid to the following:
[][]Do not touch the steam line with bare hands.
[][]Perform any kind of maintenance after switching off electrical power and also after cooling of hot pipe line.
[][]Use personal protective equipment and clothing as necessary at the time of performing cleaning/changing work.
[][]Be careful about the hot water line.
[][]Put the “UNDER MAINTENANCE” tag on an easily visible place of the system before performing maintenance.

System Description

[][]In hot water system the water of normal temperature is heated by exchanging heat with the steam. There is a plate type heat exchanger in this system. There is a safety valve in the inlet line of steam. If the steam pressure is more than 4 bar, the pressure will be released by opening the valve.

[][]The desired temperature of water can be set from the control panel. After being heated, the hot water is circulated to the AHUs and then back to the hot water systems by pump. There are two pumps for this purpose. Between these two pumps one stands by while another is running. There is a condensing unit in the system. This is used to store the condensate water.

Pre-start check

[][]The steam pressure before PRV should be 4 – 6 bar and after PRV it should be 1.5 – 2 bar.
[][]Compressed air pressure has to be 4 – 5 bar.
[][]Before starting the system, drain the water of condensing unit of hot water systems.

Starting Procedure

[][]Switch on main circuit breaker to give electrical power to the PLC.
[][]Press the button and then press the Green button on VSD to start the Hot water circulating pumps.
[][]The desired temperature of hot water can be set by pressing the up and down arrow key of control panel (see in the section 7.4.1).

During Operation

[][]The temperature of hot water can be set or changed according to the following steps:
[][]The temperature band can also be set
[][]During operation, fill up the log sheet for Monitoring of Hot Water System.

Stopping Procedure

[][]Close the steam inlet valve.
[][]Switch off the pump by pressing the red button on VSD.
[][]Switch off the main circuit breaker.

Preventive Maintenance of Hot Water System

Daily

[][]Check steam pressure.
[][]Check the water level in the hot water reservoir.
[][]Check and drain the water of condensing unit.
[][]Check the water level of expansion tank.
[][]Check for any type of leakage from hot water circulating pumps.
[][]Check if there is any vibration while running the pumps.

Weekly

[][]Check and tighten (if necessary) all the electrical connections.
[][]Check and clean all the pneumatic valves.
[][]Check and tighten all the connections of pumps.

Bimonthly

[][]Clean the float valve of condensing unit.

Monthly

[][]Check the insulation of steam line and hot water line.
[][]Check the bearing of pumps.

Annexure:

Annexure – I: Log sheet for monitoring of Hot Water Systems
Annexure – II: Log sheet for preventive maintenance of Hot Water Systems

Hot Water System Operation And Maintenance Read More »

Purified Water Generation Plant Manual Operation

Purified Water Generation Plant, Purpose:

Purified Water Generation Plant, The purpose of this SOP is to define the Manual Operation of Purified Water Generation Plant manufactured by Watertown in order to ensure its smooth & trouble-free operation and generation of qualified purified water.

Purified Water Generation Plant, Scope:

This Standard Operating Procedure applies to the PW plant manufactured by Watertown, which is located at the Utility area (roof top) of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]PW: Purified Water.
[][]HMI: Human Machine Interface.
[][]RO: Reverse Osmosis.

Responsibilities:

[][]The roles and responsibilities are as follows:

Engineering (Validation) Department

[][]Preparing the SOP and revise it when necessary.

Engineering (Maintenance) Department

[][]To provide necessary support for smooth operation of the system.

Operators

[][]To operate the PW plant according to the SOP.

Manager, Engineering

[][]To ensure that the operation of PW plant are done properly.

Manager, Quality Assurance

[][]To approve the SOP.
[][]To ensure overall implementation of this SOP.

Procedure:

Precautions:

[][]All operation work must be done safely in accordance with the requirements of the Plant Safety Statement and the safety notices around the plant. Specific attention must be paid to the following:
[][]Use Personal Protective Equipment during handling of any kind of chemical.
[][]Be careful about the hot water and steam line.
[][]Ensure all the utilities before doing any operation.

Operating Procedure:

[][]Manual operation of PW plant:
[][]Starting of PW plant:
[][]Switch on the main breaker to supply electrical power of the plant.
[][]Ensure compressed air and other utilities to run the plant.
[][]The HMI becomes ON and following screen will appear.
[][]Press Enter on that screen.
[][]Then the following screen will appear.
[][]Press “Parameter setting**” button to check the parameters and a box will appear for user ID and Password.
[][]Then the following screen will appear to see the parameters. Press “setting2” to see the other parameter settings.
[][]Then the following screen will appear.
[][]Press the “Pretreatment Flowchart” button and screen for pretreatment flowchart will appear.
[][]Press the “Manual off” button. In Manual mode the Multi Grade Filter and Active Carbon Filter will be reversely washed and then the RO will be washed by manually on Valve and pump. The softener generation also will be done manually.
[][]Reverse Washing of Multi grade filter:
[][]Active carbon filter reverse washing:
[][]Softener Regeneration:
[][]Manual Operation In RO:
[][]Press on RO Flow chart on Screen and will show following screen
[][]After 5-10 min on pump PU51-01,PU51-02,PU52
[][]Do reverse washing as it is stated for 3 minutes.
[][]Then open the valves XV51-09, XV51-06, XV52-10, XV52-09, XV52-06 and XV60-01.
[][]During Operation:
[][]To see any alarm press the “Alarm status” button in Figure 05. Following screen will appear:
[][]By pressing the button “ ” the alarms will be acknowledged and stored in the alarm history. All the alarms in the alarm history can be watched in the “History Alarm” section by pressing the Up and Down arrow.
[][]There is an online data logger which logs the conductivity of water after softener, 1st RO, 2nd RO and EDI.
[][]The real time curve can be seen by pressing the “Real Time Curve” button in Figure 05.

Stopping procedure of PW plant:

[][]To Stop Pump PU51-01,PU51-02,PU52
[][]To stop valves.
[][]After that press “Manual on” button in the “Pretreatment Flowchart status” screen (Figure 05) for stopping manual mode.
[][]Switch off the main breaker to cut the electricity.
[][]Close the line of compressed air and other utilities.

Annexure:

N/A

Purified Water Generation Plant Manual Operation Read More »

Purified Water Generation & Distribution System Maintenance

Purified Water Generation, Purpose:

Purified Water Generation, The purpose of this SOP is to define the Maintenance procedure of Purified Water Generation and Distribution System manufactured by Watertown in order to ensure its smooth & trouble-free operation and generation of qualified purified water.

Purified Water Generation, Scope:

This Standard Operating Procedure applies to the PW Generation and Distribution systems manufactured by Watertown. The Generation system of purified water is located at the utility area (roof top).

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]PW: Purified Water.
[][]HMI: Human Machine Interface.
[][]RO: Reverse Osmosis.
[][]EDI: Electro De Ionizer.
[][]ACF: Activated Carbon Filter.
[][]MGF: Multi Grade Filter.

Responsibilities:

[][]The roles and responsibilities are as follows:

Engineering (Validation) Department

[][]Preparing the SOP and revise it when necessary.

Engineering (Maintenance) Department

[][]To provide necessary support for maintenance of the system.
[][]To ensure that the operators are responsible to carry out the maintenance tasks and fill up the logbooks.

Operators

[][]To perform the maintenance of the system according to the SOP.
[][]To fill up the logbooks.

Manager, Engineering

[][]To ensure that the maintenance of PW plant are done properly.

Manager, Quality Assurance

[][]To approve the SOP.
[][]To ensure overall implementation of this SOP.

Procedure:

Precautions:

[][]All operation work must be done safely in accordance with the requirements of the Plant Safety Statement and the safety notices around the plant. Specific attention must be paid to the following:
[][]Use Personal Protective Equipment during handling of any kind of chemical.
[][]Be careful about the hot water and steam line.
[][]Ensure all the utilities before doing any operation.
[][]Hang the Maintenance tag prior to any maintenance activity.

System Description:

[][]The PW is produced from feed water through various processes. In pretreatment portion the feed water is passed through the MGF, ACF, softener and 5 micron cartridge filter. Then the pretreated water is passed through 1st and 2nd stage RO and finally through EDI. In RD/EDI section there is another 5 micron cartridge filter after 1st RO.

[][] There are four chemical dosing systems in PW Generation system such as chlorine dosing, SMBS dosing, Anti Scalant dosing and pH correction dosing. There is a PW storage tank of capacity 5000L in Solid Block.

[][]Also, there is a PW Distribution loop in the Liquid Block which contains a 3000L PW storage tank. There is a user point in the PW distribution loop system of Solid to supply the PW in the PW storage tank of Liquid Block.

Maintenance Procedure:

[][]Filter Cleaning procedure: The cartridge filter is cleaned when the filter is blocked and the pressure rises. Normally, an alarm is generated on the PLC due to high pressure (greater than 0.3MPa).
The cartridge filter is dismantled from the filter housing. Then wash the filter by passing the normal water through the filter in backward direction.
[][]Sanitize the ACF after every 14 days according to the SOP.
[][]Sanitize the 1st RO, 2nd RO and EDI after 6 months according to the SOP.
[][]Sanitize the PW distribution system after every 14 days according to the SOP.
[][]Clean the dosing tanks on every 2 weeks. At first, empty the dosing tank and wash it by PW.
[][]The maintenance schedule of PW Generation and Distribution system is given below:

[][]Daily maintenance
>>Check for any leakage.
[][]Bi monthly
>>Clean the dosing tanks.
[][]Monthly
>>Shoot clean for panel board.
[][]Yearly
>>Tighten all the nuts and bolts.
>>Check all electrical connections.
[][]After two years
>>Change the gasket of the valves.
>>Check the pneumatic pipes and change if it is necessary.
>>High pressure (greater than 0.3 MPa) across the cartridge pre filter
>>Wash the cartridge pre filter.

Annexure:

Annexure – I: Maintenance Log Sheet of PW Generation and Distribution system

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Purified Water Distribution System Operation

Purified Water Distribution System , Purpose:

Purified Water Distribution , The purpose of this SOP is to define the Operation of Purified Water Distribution System manufactured by Watertown in order to ensure its smooth & trouble-free operation and generation of qualified purified water.

Purified Water Distribution, Scope:

This Standard Operating Procedure applies to the PW Distribution systems manufactured by Watertown, which is located at the Utility area (roof top) of both General and Cephalosporin Blocks of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]PW: Purified Water.
[][]HMI: Human Machine Interface.

Responsibilities:

[][]The roles and responsibilities are as follows:

Engineering (Validation) Department

[][]Preparing the SOP and revise it when necessary.

Engineering (Maintenance) Department

[][]To provide necessary support for smooth operation of the system.
[][]To ensure that the operators are responsible to carry out the operation and fill up the logbooks.

Operators

[][]To operate the system according to the SOP.
[][]To fill up the logbooks.

Manager, Engineering

[][]To ensure that the operation of PW plant are done properly.

Manager, Quality Assurance

[][]To approve the SOP.
[][]To ensure overall implementation of this SOP.

Procedure:

Precautions:

[][]All operation work must be done safely in accordance with the requirements of the Plant Safety Statement and the safety notices around the plant. Specific attention must be paid to the following:
[][]Use Personal Protective Equipment during handling of any kind of chemical.
[][]Be careful about the hot water and steam line.
[][]Ensure all the utilities before doing any operation.

System Description:

Both the Generation and Distribution system of PW plant has been installed by Watertown. In PW distribution system purified water is circulated by a booster pump. There are a flow transmitter and a conductivity transmitter in the return line of PW which show the flow rate and conductivity of PW. The system can be operated using both the manual and automatic mode.

Operating Procedure:

[][]Automatic operation of PW Distribution system:

Starting of PW Distribution system:

[][]Switch on the main breaker to supply electrical power of the plant.
[][]Ensure compressed air and other utilities to run the plant.
[][]Switch ON the UPS. In case of emergency stop, release the emergency stop switch.
[][]Then starting page will appear and press on HMI.
[][]Then the following screen will appear. Press “Control flow”.
[][]Press the “Automatic Cycle OFF” and give user ID and password.
[][]Press the “Automatic Cycle OFF” again to start the system in automatic mode. When the system is started, the “Automatic Cycle OFF” turns into “Automatic Cycle ON” and the booster pump becomes ON.

During Operation:

[][]To see any alarm press the “Alarm” in Figure 02.
[][]By pressing the “ ” the alarms will be acknowledged and stored in the alarm history.
[][]Press the “Parameters Set” to see and change the set parameter.
[][]The Daily Operational Log Sheet (Annexure – I and II) of PW distribution system will be filled up on every hour by the operator. Photocopy of all the approved forms will be used where easily applicable. For the cases where computer generated copies are relatively easy to handle, the exact format of the approved form can be used(except the approval sign) with the following notes as footer:
“This is a computer generated report. The format is as per the original approved form.”

Stopping of PW distribution system:

[][]Press the “Automatic Cycle ON” of on HMI. The booster pump will shut down.
[][]Switch OFF the UPS.
[][]Switch OFF the main circuit breaker.
[][]In case of emergency press the emergency switch.

Manual operation of PW distribution system:

[][]Starting of PW distribution system:
[][]Follow the steps of one to five of section
[][]Press the “Manual Cycle OFF” and give user ID and password on HMI (figure 02). Again press the “Manual Cycle OFF” and it turns to “Manual Cycle ON”.
[][]Switch ON the booster pump, pneumatic valves of vent filter and return line by pressing the ON button of each component on HMI.

Stopping procedure of PW distribution system:

[][]Switch off the booster pump and pneumatic valves of vent filter and return line.
[][]Press the “Manual Cycle ON”.
[][]Switch OFF the UPS.
[][]Switch OFF the main circuit breaker.
[][]In case of emergency, press the emergency switch.

Annexure:

Annexure – I: Operational Log Sheet of PW Distribution system

Purified Water Distribution System Operation Read More »

Reverse Washing of MGF, ACF & Regeneration of Softener In Manual Mode

Reverse Washing, Purpose:

Reverse Washing, The purpose of this SOP is to define the Reverse washing of MGF, ACF and regeneration of softener of PW Generation system in manual mode.

Scope:

This Standard Operating Procedure applies to the PW plant manufactured by Watertown, which is located at the Utility area (roof top) of General Block of Labaid Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]PW: Purified Water.
[][]HMI: Human Machine Interface.
[][]MGF: Multi Grade Filter.
[][]ACF: Active Carbon Filter.

Responsibilities:

[][]The roles and responsibilities are as follows:

Engineering (Validation)

[][]Preparing the SOP and revise it when necessary.

Engineering (Maintenance) Department

[][]To provide necessary support for smooth operation of the system.

Operators

[][]To operate the PW plant according to the SOP.

Manager, Engineering

[][]To ensure that the operation of PW plant are done properly.

Manager, Quality Assurance

[][]To approve the SOP.
[][]To ensure overall implementation of this SOP.

Procedure:

Precautions:

[][]All operation work must be done safely in accordance with the requirements of the Plant Safety Statement and the safety notices around the plant. Specific attention must be paid to the following:
[][]Use Personal Protective Equipment during handling of any kind of chemical.
[][]Be careful about the hot water and steam line.
[][]Ensure all the utilities before doing any operation.

Operating Procedure:

Manual Reverse Washing of MGF:
[][]Switch on the main breaker to supply electrical power of the plant.
[][]Ensure compressed air and other utilities to run the plant.
[][]The HMI becomes ON and following screen will appear.
[][]Press Enter on that screen.
[][]Press the “Pretreatment Flowchart” button and screen for pretreatment flowchart will appear.
[][]Press the “Manual off” button and give USER ID and Password.
[][]On Valve by pressing on Valve position on screen (figure-05) XV44-04, XV44-05, and XV20-02.
[][]Set frequency (0-50Hz) PU30B/PU30A.
[][]ON Pump by pressing on pump position.
[][]After 5-10 min off the pump by pressing on pump position.
[][]On valve by pressing on valve position on screen XV44-01, XV44-03.
[][]Pump ON.
[][]Reverse washing of MGF is performed for 10 minutes. Depositing and observe washing of MGF is performed for 2 minutes and 5 minutes respectively.

Active Carbon Filter Reverse Washing:

[][]OFF Valve XV44-03
[][]ON Valve XV44-02
[][]ON Valve XV45-04,XV45-05
[][]After 5-10 min Pump off.
[][]On Valve XV45-01,XV45-03
[][]After 0-10 min OFF valve XV45-03
[][]On Valve XV45-02
[][]After 5-10 min will go to softener operation.
[][]The time for reverse washing, depositing and observe washing is as same as MGF.

Softener Regeneration:

[][]For back washing of softener A ON the valve XV50-04A and XV50-05A. Backwashing will be performed for 10 minutes.
[][]After backwashing during regeneration ON the valves XV50-01A, XV50-15, XV50-14A, XV50-03A. Regeneration will be performed for 50 minutes.
[][]For observe washing ON the valves XV50-01A, XV50-03A. Observe washing will be performed for 50 minutes.
[][]Backwashing, regeneration and observe washing procedure of softener B is same as softener B.

Reverse Washing of RO:

[][]Press on RO Flow chart on Screen and will show following screen
[][]After 5-10 min on pump PU51-01,PU51-02,PU52
[][]On valve XV51-07, XV51-05, XV52-06, XV52-07 and XV52-05.

Annexure:

N/A

Reverse Washing of MGF, ACF & Regeneration of Softener In Manual Mode Read More »

Purified Water Distribution System Sanitization in Manual Mode

Purified Water Distribution System, Purpose:

Purified Water Distribution System, The purpose of this SOP is to define the sanitization procedure of purified water distribution system in manual mode.

Purified Water Distribution System, Scope:

This Standard Operating Procedure applies to the PW Distribution systems manufactured by Watertown, which is located at the Utility area (roof top) of  XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]PW: Purified Water.
[][]HMI: Human Machine Interface.

Responsibilities:

[][]The roles and responsibilities are as follows:

Engineering (Validation) Department

[][]Preparing the SOP and revise it when necessary.

Engineering (Maintenance) Department

[][]To provide necessary support for smooth operation of the system.
[][]To ensure that the operators are responsible to carry out the operation according to the SOP.
[][]To inform PW user departments not to open the valves during sanitization.

Operators

[][]To operate the system according to the SOP.

Manager, Engineering

[][]To ensure that the operation of PW plant are done properly.

Manager, Quality Assurance

[][]To approve the SOP.
[][]To ensure overall implementation of this SOP.

Procedure:

Precautions:

[][]All operation work must be done safely in accordance with the requirements of the Plant Safety Statement and the safety notices around the plant. Specific attention must be paid to the following:
[][]Be careful about the hot water and steam line.
[][]Ensure all the utilities before doing any operation.
[][]Do not touch the steam and hot water line with bare hands.
[][]Do not open any valve of distribution line during sanitization.
[][]Ensure at least 35% water level in the PW storage tank before doing sanitization.

System Description:

[][]There are two distribution systems of purified water in cephalosporin and general block. There is a shell and tube type heat exchanger in distribution loop to sanitize the system. During sanitization, purified water is heated using industrial steam at a temperature of 80⁰C. Then this hot water is circulated through distribution loop for a period of 60 minutes. Cooling is done after sanitization at a temperature of 40⁰C using chilled water.

Sanitization Procedure:

Prestart check:

[][]Ensure minimum 3 bar industrial steam pressure before starting sanitization.
[][]Chilled water temperature has to be less than 10⁰C.
[][]Close all the valves of distribution line and inform all the PW user departments not to open the valve during sanitization period.
[][]Check the water level in the PW storage tank. It has to be minimum 35%.
[][]Open the steam inlet valve manually before starting sanitization

Starting of Sanitization system in manual mode:

[][]Switch on the main breaker to supply electrical power of the plant.
[][]Ensure compressed air and other utilities to run the plant.
[][]Switch ON the UPS. In case of emergency stop, release the emergency stop switch.
[][]Then starting page will appear and press “ENTER” on HMI.
[][]Then the following screen will appear. Press “Control flow”.
[][]Press the “Manual Cycle OFF” and give user ID and password.
[][]Press the “Manual Cycle OFF” again to start the system in manual mode.
[][]Open the vent valve and PW inlet valve of storage tank and switch ON the distribution pump by pressing the ON button on HMI.
[][]Open the pneumatic valve of steam inlet and condensate outlet of heat exchanger. See the next figure:

#Open the valves and start the pump

#Open the valves to start sanitization.

[][]Press the “Sanitization OFF” button to start the sanitization.
[][]Wait until the temperature of PW increases up to 80⁰C. When the temperature reaches at 80⁰C, close the steam inlet valve and condensate outlet valve.
[][]Circulate the PW through the distribution loop for an hour.

[][]Cool down the temperature of PW less than 40 deg.C. Fill up the log sheet during sanitization on every 30 minutes.
[][]After cooling down close all the valves and distribution pump.
[][]Switch off the UPS.
[][]Switch off the circuit breaker.
[][]Sanitization Frequency:
[][]Initially, the sanitization will be performed after every 20 days.
[][]Sanitization frequency will be finally determined after completion of phase – 3 of performance qualification of PW.
[][]If the plant remains closed for any long vacation, then the distribution system will be sanitized.

Annexure:

[][]N/A

Purified Water Distribution System Sanitization in Manual Mode Read More »

WFI generation system operation

WFI generation system operation, Purpose

WFI generation system operation, The purpose of this procedure is to provide directions for operating the WFI generation System.

WFI generation system operation, Scope

This SOP applies to the WFI generation system which is located at the roof top area of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]HMI: Human Machine Interface

Responsibilities:

[][]The roles and responsibilities are as follows

Engineering ( Validation) Department

[][]To prepare the SOP & revise it when necessary.

Engineering (Maintenance) Department

[][]To provide necessary support for smooth operation of the system.
[][]To ensure that the operators are responsible to carry out the operation and fill up the logbooks.

Operators/Technician

[][]To operate the WFI generation system according to the SOP.
[][]To fill up the logbooks related to the PW plant.

Manager, Engineering

[][]To ensure that the operation of PW plant are done properly.

Manager, Quality Assurance

[][]To approve the SOP.
[][]To ensure overall implementation of this SOP.

Procedure

Precautions:

[][]The tank walls are hot. The water in the tank is at 80°C when the unit is operating. Contact with 80°C water will cause burns.
[][]The piping system is under pressure .Causing an open in the systems pressurized piping without taking suitable precaution may release medium pressure (60+psig).
[][]Running the pump without water in it will burn out the motor after only a few seconds, and it may cause the pump to seize as well.

Operation of WFI generation Plant

[][]Starting Procedure of WFI Generation System:
[][]Switch on the main breaker to supply electrical power of the plant.
[][]Ensure compressed air and other utilities to run the plant.
[][]The HMI becomes ON and following screen will appear.
[][]Press Start on that screen.
[][]Press User key. After that following screen will appear
[][]Press on Press on “Parameter set” for Parameter Setting. After pressing on this key will show the following screen.

Automatic Operation:

[][]After parameter setting, Back to previous screen and Press on “flow chart status”. If there is no need to parameter setting avoid the procedure.After pressing the flow chart status key following figure will be shown below. After that Press on the “Auto” for on the system in automatic operation.

Manual operation:

After parameter setting, Back to previous screen and Press on “Flowchart Status” for ON the system for manual operation. If there is no need to parameter setting avoids the procedure. After pressing the flowchart status key figure-III will be shown. If the system is on in Automatic mode must off the system. Press on the “Manual” for on the system in manual mode. After that ON Pump (PU01), ON valve PASV501, PASV201, and PDMV402.Other controlling Valve operate Operator according to the condition of the system.

Check during operation

[][]Check WFI Temperature.
[][]Check Steam pressure.
[][]Check that there is no unusual noise or vibration. Stop and investigate if found.
[][]The Operational Log Sheet (Annexure – I) of WFI generation system will be filled up by the operator. Photocopy of all the approved forms will be used where easily applicable. For the cases where computer generated copies are relatively easy to handle, the exact format of the approved form can be used(except the approval sign) with the following notes as footer:
“This is a computer generated report. The format is as per the original approved form.”

[][]Stopping Procedure of WFI distribution System

Automatic Operation:

[][]if plant is running on Automatic mode then stops the system by pressing on the key Auto. Then power off by turning to off position in circuit breaker.

Manual Operation:

[][]At first turn off the pump. After that stop valve PASV50, PASV201, and PDMV402. The system stop by pressing on the key Manual. Then power off by turning to off position in circuit breaker.

Annexure

Annexure-I: Operational Log sheet of WFI Generation System.

WFI generation system operation Read More »

WFI distribution system operation

WFI distribution system, Purpose

WFI distribution system, The purpose of this procedure is to provide directions for operating the WFI Distribution System

WFI distribution system, Scope

This SOP applies to the WFI distribution system which is located at the roof top area of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.

Responsibilities:

[][]The roles and responsibilities are as follows

Engineering ( Validation) Department

[][]To prepare the SOP & revise it when necessary.

Engineering (Maintenance) Department

[][]To provide necessary support for smooth operation of the system.
[][]To ensure that the operators are responsible to carry out the operation and fill up the logbooks.

Operators/Technician

[][]To operate the WFI distribution system according to the SOP.
[][]To fill up the logbooks related to the PW plant.

Manager, Engineering

[][]To ensure that the operation of PW plant are done properly.

Manager, Quality Assurance

[][]To approve the SOP.
[][]To ensure overall implementation of this SOP.

Procedure

Precautions:

[][]The tank walls are hot. The water in the tank is at 80°C when the unit is operating. Contact with 80°C water will cause burns.
[][]The piping system is under pressure. Causing an open in the systems pressurized piping without taking suitable precaution may release medium pressure (60+psig).
[][]Running the pump without water in it will burn out the motor after only a few seconds, and it may cause the pump to seize as well.
[][]There is one electrical panel for the distribution system. The PLC panel has 110V power in it. Precautions should be taken to avoid contact with the 110V power line. The remainder of the panel is at 24V.
[][]The panel inside is installed a VFD. It has an external power. It is unsafe to open the panel with power (415V) ON. Only knowledgeable service technicians should operate the VFD.

System Description

[][]Distribution skid and distribution piping will contribute to WFI distribution system.
[][]Distribution skid
[][]Distribution pump, system, sampling valves, instruments and control panel will be mounted on skid. The skid frame is constructed from 304 grade stainless steel.

Pump:

[][]Pump will be designed and selected according to cGMP requirement for velocity, flow and contact parts. Pressure gauge at the discharge will monitor the pressure.

Three way Pneumatic valve:

[][]Flow diverter valves are provided at the supply line and return line of distribution system. If conductivity of water is greater than the set point of conductivity transmitter provided at supply & return line of distribution system, drain port of this valve will open and in turn will not allow quality deteriorated water to go to the point of use & to the system.

Distribution Piping

[][]The whole distribution system is fabricated and installed as per cGMP. Distribution system is fabricated out of SS316L tubes and tube fittings (sanitary type). The distribution loop consists of 5 user points. The user point valves are zero dead leg valves. Orifice plates are provided at each point of use to maintain specific flow. The return line of distribution system is connected back to the top of the storage tank with the spray ball provided inside the tank.

Operation of WFI Plant

[][]Starting Procedure of WFI Distribution System:
[][]Switch on the main breaker to supply electrical power of the plant.
[][]Ensure compressed air and other utilities to run the plant.

[][]The HMI becomes ON and screen will appear.

[][]Over the window Touch this[ENTER] key

[][]Press Enter on that screen . After that a screen will appear

[][]Over the screen Press on “Parameter set” for Parameter Set.

[][]Press on “Alarm” for Alarm check

[][]Press on “Control Flow” for ON the system

[][]Press on Press on “Parameter set” for Parameter Setting. After pressing on this key will show a screen.

[][]Press on BACK for return of the previous screen

Automatic Operation:

[][]After parameter setting, Back to previous screen and Press on “Control Flow”. If there is no need to parameter setting avoid the above procedure .After pressing the Control Flow key a screen will appear.

Two option will show the screen

1.0 “Automatic Cycle”

2.0 Press on “Manual cycle”

[][]Press on the “Automatic cycle” for on the system in automatic operation.

Manual operation:

[][]After parameter setting, Back to previous screen and Press on “Control Flow” for ON the system for manual operation. If there is no need to parameter setting avoids the above procedure  . After pressing the ‘Control Flow’  will be shown. If the system is on in Automatic mode must off the system. Press on the Manual cycle for on the system in manual mode. After that ON Pump (PU300), ON WFI inlet valve in WFI tank.

Check during operation

[][]Check that there is no unusual noise or vibration. Stop and investigate if found.
[][]The Operational Log Sheet (Annexure – I) of WFI distribution system will be filled up by the operator. Photocopy of all the approved forms will be used where easily applicable. For the cases where computer generated copies are relatively easy to handle, the exact format of the approved form can be used(except the approval sign) with the following notes as footer:
“This is a computer generated report. The format is as per the original approved form.”

Stopping Procedure of WFI distribution System

[][]Automatic Operation: if plant is running on Atomatic mode then stops the system by pressing on the key Automatic cycle. Then power off by turning to off position in circuit breaker.
[][]Manual Operation: At first turn off the circulating pump and WFI inlet valve from distribution loop. After that stops the system by pressing on the key Manual cycle. Then power off by turning to off position in circuit breaker.

Annexure

Annexure I Operational log Sheet of WFI Distribution System

WFI distribution system operation Read More »

WFI Generation and Distribution System Maintenance

WFI Generation and Distribution, Purpose:

WFI Generation and Distribution, The purpose of this SOP is to define the Maintenance of WFI Generation & Distribution System manufactured by Watertown in order to ensure its smooth & trouble-free operation.

WFI Generation and Distribution, Scope:

This Standard Operating Procedure applies to the WFI Generation & Distribution system manufactured by Watertown, which is located at the Utility area (roof top) of Cephalosporin Block of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure
[][]WFI: Water For Injection
[][]HMI: Human Machine Interface
[][]PTFE: Poly Tetra Fluro Ethin

Responsibilities:

[][]The roles and responsibilities are as follows:

Engineering (Validation) Department

[][]Preparing the SOP and revise it when necessary.

Engineering (Maintenance) Department

[][]To provide necessary support for smooth maintenance of the system.
[][]To ensure that the operators are responsible to carry out the maintenance and fill up the logbook.

Operators/Technician

[][]To perform maintenance of the system according to the SOP.
[][]To fill up the logbooks.

Manager, Engineering

[][]To ensure that the maintenance of PW plant are done properly.

Manager, Quality Assurance

[][]To approve the SOP.
[][]To ensure overall implementation of this SOP.

Procedure:

Precautions:

[][]All maintenance work must be done safely in accordance with the requirements of the Plant Safety Statement and the safety notices around the plant. Specific attention must be paid to the following:

[][]Use Personal Protective Equipment during handling of any kind of chemical.
[][]Be careful about the hot water and steam line.

Maintenance Schedule:

[][]The maintenance schedule of WFI generation and distribution system is given below:

Daily maintenance

[][]Check for any leakage in steam line or WFI line.

After 800 hrs.

[][]Check and clean the filter/strainer.
[][]Check and clean the steam traps.
[][]Check the safety valve.
[][]Clean the storage tanks.

After 8000 hrs.

[][]Check the PTFE gaskets on the membrane valve and replace it if necessary.
[][]Check the diaphragm valves and change the diaphragm if it is necessary.
[][]Check the gaskets of heat exchangers.
[][]Check the mechanical seals of pump.
[][]Change the vent filter cartridge.

Annexure:

Annexure – I: Maintenance Log Sheet of WFI Generation and Distribution system 

WFI Generation and Distribution System Maintenance Read More »

ETP Operation Procedure

ETP Operation, Purpose:

ETP Operation, The purpose of this SOP is to define the standard operating procedure of Effluent Treatment Plant of XX Pharmaceuticals Ltd.

ETP Operation, Scope:

This Standard Operating Procedure applies to the Effluent Treatment Plant of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]ETP: Effluent Treatment Plant.
[][]PPE: Personal Protective Equipment.
[][]PAC: Poly Aluminum Chloride.
[][]MGF: Multi Grade Filter.
[][]ACF: Activated Carbon Filter.

Responsibilities:

Engineering (Validation) Department

[][]Preparing the SOP and revise it when necessary.

Engineering (Maintenance) Department

[][]To provide necessary support for smooth operation of the system.
[][]To ensure that the operators are responsible to carry out the operation and regular checking of the critical components.

Operators

[][]To operate the ETP according to this SOP.

Manager, Engineering

[][]To ensure that the operation of ETP are done properly.

Manager, Quality Assurance

[][]To ensure overall implementation of this SOP.

Procedure:

Precautions:

[][]All operation work must be done safely in accordance with the requirements of the Plant Safety Statement and the safety notices around the plant. Specific attention must be paid to the following:
[][]Handle the chemicals by wearing PPE.
[][]Ensure all the utilities before doing any operation.

System Description:

[][]The capacity of ETP is 12000 Ltr/hr. The effluents from the Solid and Liquid block come into the neutralization and equalization tanks respectively via bar screen chambers. In the bar screen chamber the floating material or solid material is filtered. A dosing of lime is provided in the neutralization tank if pH correction is needed.

[][]Also, the effluents are aerated in these tanks with air which is provided by the blowers. After being neutralized in the neutralization tank the effluents goes to equalization tank and then the effluent is transferred to flocculation tank through effluent transfer pumps.
[][]A dosing of PAC is provided in flocculation tank to flocculate all the effluents. Poly electrolyte dosing is provided in the transferring pipe of effluents from flocculation tank to lamella. After lamella the effluent is passed to the aeration tank.
[][]In aeration tank the effluents are aerated with air. A dosing of NaOH is provided if it is necessary. There is a buffer tank after aeration tank where one kg of urea will be provided after every 3 months of operation.
[][]There is a line under the buffer tank to transfer the sludge to underground sludge tank and then to sludge pit by sludge transfer pump.
[][]Clear water from buffer tank is stored in the clear water tank. There are two pumps to transfer the clear water to final storage tank through MGF and ACF. One pump is used at a time.

Operating Procedure:

Starting of ETP:

[][]Perform backwash of Multi Grade Filter for 15 minutes and Active Carbon Filter for 15 minutes daily before starting the plant by clean water.
[][]Switch ON the main breaker.
[][]Switch On the Blower A/B, effluent transfer pump 1/2 (alternative), Clean water transfer pump 1/2 (alternate) and keep the position of each switch in Auto mode. The dosing pumps of lime, PAC and polyelectrolyte are synchronized with the effluent transfer pumps. When the effluent transfer pumps are switched on those dosing pumps are started and vice versa. The dosing pump of NaOH is started manually when necessary.
[][]There are two float switches in the equalization and clear water tanks. When the equalization tank level will be high the effluent transfer pump will be switched on automatically and effluents will be transferred to flocculation tank.
[][]At that time, the Polyelectrolyte, PAC and lime dosing will be started automatically. If the equalization tank level becomes low, the pump will be switched off automatically.
[][]If the clean water tank level becomes high, the clean water transfer pump will be switched on and effluent transfer pump will be switched off automatically. When the level of clean water tank becomes low the clean water transfer pump will be switched off and effluent transfer pump will be switched on automatically.
[][]The effluent is transferred from flocculation tank to clear water tank via lamella, aeration tank and buffer tank by overflow of each tank.
[][]The blowers are changed over automatically after 10 minutes of operation if the main switch remains in Auto position.
[][]After 8 days of operation switch ON the sludge transfer pump to transfer the sludge to the sludge pit.

During operation:

[][]During operation fill up the operational log sheet (Annexure – I) on every hour.
[][]Check the dosing tank level.

Stopping procedure:

[][]Switch OFF the effluent transfer pumps and blowers.
[][]Switch OFF the clear water transfer pumps.
[][]Switch OFF the dosing pumps.

Annexure:

Annexure – I: Daily Operational Log Sheet of ETP.

ETP Operation Procedure Read More »

WFI Distribution System Sterilization In Automatic Mode

WFI Distribution, Purpose:

WFI Distribution, The purpose of this SOP is to define the sterilization procedure of WFI distribution system in automatic mode.

WFI Distribution, Scope:

This Standard Operating Procedure applies to the WFI Distribution system manufactured by Watertown, China located at the Utility area  of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]WFI: Water For Injection.
[][]HMI: Human Machine Interface.

Responsibilities:

[][]The roles and responsibilities are as follows:

Engineering (Validation) Department

[][]Preparing the SOP and revise it when necessary.

Engineering (Maintenance) Department

[][]To provide necessary support for smooth operation of the system.
[][]To ensure that the operators are responsible to carry out the operation and fill up the logbooks.
[][]To inform WFI user departments not to open the valves during sterilization.

Operators

[][]To operate the system according to the SOP.
[][]To fill up the logbooks properly.

Manager, Engineering

[][]To ensure that the operation of WFI plant are done properly.

Manager, Quality Assurance

[][]To approve the SOP.
[][]To ensure overall implementation of this SOP.

Procedure:

Precautions:

[][]All operational work must be done safely in accordance with the requirements of the Plant Safety Statement and the safety notices around the plant. Specific attention must be paid to the following:
[][]Be careful about the hot water and steam line.
[][]Ensure all the utilities before doing any operation.
[][]Do not touch the steam and hot water line with bare hands.

[][]Inform the respective departments i.e. Production, Microbiology, Quality Control not to open any valve of distribution line during sterilization.
[][]Ensure at least 40% water level is present in the WFI storage tank before doing sterilization.

System Description:

[][]The WFI distribution system is sterilized at a temperature of 121⁰C. WFI is heated up by using industrial steam. Heated WFI is circulated for 1 hour. After completing the sterilization distribution line is cooled down. The cooling temperature is 90⁰C. Chilled water is used to cool the WFI.

Sterilization Procedure:

Prestart check:
[][]Ensure minimum 3 bar industrial steam pressure before starting sterilization.
[][] Chilled water temperature has to be less than 10⁰C.
[][]Close all the valves of distribution line.
[][]Starting of Sterilization system in automatic mode:
[][]Open the steam inlet valve manually before starting sterilization.
[][]Switch on the main breaker to supply electrical power of the plant.
[][]Switch ON the UPS. In case of emergency stop, release the emergency stop switch.
[][]Then starting page will appear and press ENTER on HMI.
[][]Then a page will be displayed on HMI and press “Control flow”.
[][]Press the “Sanitization OFF” and give user ID and password.
[][]Press the “Sanitization OFF” again to start the system in automatic mode.

During Sterilization:

[][]During sterilization WFI is circulated through the distribution line at minimum 121oC.
[][]Fill up the log sheet (Annexure – I) during sterilization after every 20 minutes.
[][]Photocopy of all the approved forms will be used where easily applicable. For the cases where computer generated copies are relatively easy to handle, the exact format of the approved form can be used(except the approval sign) with the following notes as footer:

“This is a computer generated report. The format is as per the original approved form.”

After Sterilization:

[][]Drain all the water from the user points.
[][]Fill up the WFI storage tank with fresh WFI by running WFI Generation system.

Sterilization Frequency:

[][]The sterilization of WFI loop will be performed every 30 days.
[][]If the plant remains closed for any long vacation, then the distribution system will be sanitized.

Annexure:

Annexure – I: Operational Log Sheet of Sterilization of WFI distribution system.

WFI Distribution System Sterilization In Automatic Mode Read More »

Storage Tanks Cleaning for Generation & Distribution Systems of water

Storage Tanks Cleaning, Purpose:

Storage Tanks Cleaning, The purpose of this SOP is to define the cleaning procedure of all the intermediate storage tanks and final storage tanks of PW and WFI generation and distribution systems of XX Pharmaceuticals Ltd.

Storage Tanks Cleaning, Scope:

This Standard Operating Procedure applies to the intermediate and final storage tanks of PW and WFI generation and distribution systems  of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]WFI: Water For Injection.
[][]PW: Purified Water.

Responsibilities:

[][]The roles and responsibilities are as follows:

Engineering (Validation) Department

[][]Preparing the SOP and revise it when necessary.

Engineering (Maintenance) Department

[][]To provide necessary support for smooth cleaning of the tanks.
[][]To ensure that the operators are responsible to carry out the cleaning and fill up the logbook.

Operators/technician

[][]To perform cleaning of the system according to the SOP.
[][]To fill up the logbooks.

Manager, Engineering

[][]To ensure that the cleaning procedure of all the storage tanks are done properly.

Manager, Quality Assurance

[][]To approve the SOP.
[][]To ensure overall implementation of this SOP.

Procedure:

Precautions:

[][]All maintenance work must be done safely in accordance with the requirements of the Plant Safety Statement and the safety notices around the plant. Specific attention must be paid to the following:
[][]Use Personal Protective Equipment during handling of any kind of chemical.
[][]Be careful about handling of toxic chemicals.
[][]Be careful when climbing using a ladder to reach at the top of the tank.

Cleaning Procedure:

[][]The cleaning procedure of intermediate and final storage tanks of both PW and WFI generation and distribution systems are stated below:
[][]Open the tip of the tank about 2 hours before cleaning.
[][]Close the inlet valve of the tank.
[][]Open the discharge valve at the bottom of the tank and make the tank empty.
[][]Wash the inside wall and ground floor of the tank with bleaching powder with the help of nylon brush.
[][]Spray fresh water into the wall thoroughly to remove dirt from the wall.
[][]Clean the level sensor of the tank.
[][]Drain out the dirty water.
[][]After successful completion of the cleaning procedure, dry inside of the tank.
[][]Storage tank is now ready for use.
[][]After cleaning of PW intermediate and final storage tanks record the cleaning in the Annexure – I. Also, for WFI storage tank record the cleaning in the Annexure – I
[][]The tanks will be cleaned after 800 hrs of operation of the plant.

Annexure:

N/A

Storage Tanks Cleaning for Generation & Distribution Systems of water Read More »

WFI Distribution System Sterilization In Manual Mode

WFI Distribution System Sterilization, Purpose:

WFI Distribution System Sterilization, The purpose of this SOP is to define the sterilization procedure of WFI distribution system in manual mode.

WFI Distribution System Sterilization, Scope:

This Standard Operating Procedure applies to the WFI Distribution systems manufactured by Watertown, which is located at the Utility area of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]WFI: Water For Injection.
[][]HMI: Human Machine Interface.

Responsibilities:

[][]The roles and responsibilities are as follows:

Engineering (Validation) Department

[][]Preparing the SOP and revise it when necessary.

Engineering (Maintenance) Department

[][]To provide necessary support for smooth operation of the system.
[][]To ensure that the operators are responsible to carry out the operation according to the SOP.
[][]To inform WFI user departments not to open the valves during sterilization.

Operators

[][]To operate the system according to the SOP.

Manager, Engineering

[][]To ensure that the operation of WFI plant are done properly.

Manager, Quality Assurance

[][]To approve the SOP.
[][]To ensure overall implementation of this SOP.

Procedure:

Precautions:

[][]All operational work must be done safely in accordance with the requirements of the Plant Safety Statement and the safety notices around the plant. Specific attention must be paid to the following:
[][]Be careful about hot water and steam line.
[][]Ensure all the utilities before doing any operation.
[][]Do not touch the steam and hot water line with bare hands.
[][]Do not open any valve of distribution line during sterilization.
[][]Ensure at least 40% water level in the WFI storage tank before doing sterilization.

System Description:

[][]The WFI distribution system is sterilized at a temperature of 121⁰C. WFI is heated up by using industrial steam. Heated WFI is circulated for 1 hour. After completing the sterilization distribution line is cooled down. The cooling temperature is 90⁰C. Chilled water is used to cool the WFI.

Sterilization Procedure:

Prestart check:
[][]Ensure minimum 3 bar industrial steam pressure before starting sterilization.
[][] Chilled water temperature has to be less than 10⁰C.
[][] Close all the valves of distribution line and inform all the WFI user departments not to open the valve during sterilization period.
[][]Check the water level in the WFI storage tank. It has to be minimum 40%.
[][]Open the steam inlet valve manually before starting sterilization.

Starting of Sterilization system in manual mode:

[][]Switch on the main breaker to supply electrical power of the plant.
[][]Ensure compressed air and other utilities to run the plant.
[][]Switch ON the UPS. In case of emergency stop, release the emergency stop switch.
[][]Then starting page will appear and press ENTER on HMI.
[][] Then a page will be displayed on HMI and press “Control flow”.
[][] Press the “Manual Cycle OFF” and give user ID and password.
[][]Press the “Manual Cycle OFF” again to start the system in manual mode.
[][]Open the vent valve and WFI return valve of storage tank and switch ON the distribution pump by pressing the ON button on HMI.
[][]Open the pneumatic valve of steam inlet and condensate drain valve.
[][]Press the “Sanitization OFF” button to start the sterilization.
[][]Wait until the temperature of WFI increases up to 121⁰C. When the temperature reaches at 121⁰C, close the steam inlet valve and condensate outlet valve.
[][]Circulate the WFI through the distribution loop for an hour.

Sterilization Period:

[][]During sterilization WFI is circulated through the distribution line at 121 ⁰C. If the temperature drops then open the steam inlet and condensate outlet valve to heat up the WFI.
[][]Fill up the log sheet (Annexure – I ) during sterilization every 20 minutes.

 Cooling Period:

[][]After completion of sterilization, switch OFF all the steam valves.
[][]Switch ON the pneumatic valves of cooling water in and cooling water out by pressing the ON button on HMI.
[][]Cool down the temperature of WFI less than 90 deg.C. Fill up the log sheet (Annexure – I ) during total sterilization period on every 20 minutes.
[][]After cooling down close all the valves and distribution pump.
[][]Switch off the UPS.
[][]Switch off the circuit breaker.

After Sterilization:

[][]Drain all the water from the user points.
[][]Fill up the WFI storage tank with fresh WFI by running WFI Generation system.

Sterilization Frequency:

[][]The sterilization of WFI loop will be performed every 30 days.
[][]If the plant remains closed for any long vacation, then the distribution system will be sanitized.

Annexure:

N/A

WFI Distribution System Sterilization In Manual Mode Read More »

HEPA Filters Numbering System

HEPA Filters Numbering, Purpose:

HEPA Filters Numbering, The purpose of this SOP is to define the procedure for the establishment of identification number of G4, F5, F7, F9 and HEPA filters of any machine (except HVAC system) of XX Pharmaceuticals Ltd.

HEPA Filters Numbering, Scope:

The G4, F5, F7, F9 and HEPA filters of any machine of all area of XX Pharmaceuticals Ltd are covered by this SOP.

Definitions / Abbreviation:

[][]N/A

Responsibilities:

[][]The roles and responsibility are as follows:

Engineering Person

[][]To fill up the request form (Annexure – 1) to get the ID of filters of newly installed machines.
[][]To inform validation (engineering) department if there is any replacement of filters.

Engineering (Validation) Department

[][]To give the ID of filters.

Functional Head

[][]To ensure that all the filters of machines are numbered according to this SOP and any Inclusion or Exclusion will be reported to the Validation (Engineering) department within 7 days of Inclusion/Exclusion.

Quality Assurance

[][]To ensure overall implementation of this SOP.

Procedure:

Filter Numbering

[][]Filters will be numbered using the following convention:
AAAA – BBB – CCC – XXX
Where,
[][]AAAA/AAA/AA: 4/3/2 characters to indicate the area of the plant. (See the Annexure – I )
[][]BBB: 3 digits numerical code to indicate the machine. (See the Annexure – II)
[][]CCCC/CCC: 4/3 characters to indicate the grade and type of filter (see Annexure – I). First 2/3 characters indicates the grade of filters and last character indicates the type of filter (bag type, flat type etc.).
[][]XXX: Three digits numerical code to indicate the sequential number of the same type of filter of that machine.
[][]For an example, a flat type HEPA filter of grade H14 of Dispensing booth of production area of Solid Block will be numbered according to the following way:

SPRD – 030 – H14F – 001

[][]001 =Sequential Number for that filter

[][]H14F=H14 Grade and Flat type HEPA filter.

[][]030=Numerical code of dispensing booth

[][]SPRD=Solid Production Area

[][]All G4, F5, F7, F9 and HEPA filters of Machines will be tagged containing ID number. Format of filter identification tag is as follows:

ID Number:

[][]The length and height of the box is 4.0 inch and 0.4 inch respectively. Arial font of size 10 shall be used for all the letters. A register ID numbers of filters will be maintained by the validation (Engg.) department.

[][]To get the ID of newly installed filters, the request form for ID (Annexure – II) will be filled up by the respective engineers and sent to the validation (engineering) department. Validation department will provide the sticker of ID and photocopy of the request form after giving new ID.

[][]If a Filter is replaced with a new one, the ID of previous one will be used for the new filter. For this, the respective engineering person will inform the validation (engineering) department and validation engineer will update the Filter list with the newly fitted one and replacement will be noted in the remarks section.

[][]If any filter of new grade (which is not in the list of Annexure – I) is installed, the Annexure – I will be updated by handwriting of Manager, QA with signature and date. The new grade filter will be added on the next version of SOP.

[][]Photocopy of all the approved forms will be used where easily applicable. For the cases where computer generated copies are relatively easier to handle, the exact format of the approved form can be used (except the approval sign) with the following notes as footer:

“This is a computer generated report. The format is as per the original approved form”

Annexure:

Annexure-I : Code for Grade and Type of Filters.
Annexure-II : Request Form for ID Number of filters.
Annexure–III: Register of filters.

HEPA Filters Numbering System Read More »

Gas Generator Operation & Maintenance

Gas Generator, Purpose:

Gas Generator, The purpose of this SOP is to define the operation and maintenance of the 1500 KW gas generator of XX Pharmaceuticals Ltd.

Gas Generator, Scope:

This SOP applies to the Cummins generator of capacity 1500 KW (Model: QST30-G4) which is located at General block of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]EHS : Environment Health and Safety
[][]PPE : Personal Protective Equipment
[][]SOP : Standard Operating Procedure

Responsibilities:

[][]The roles and responsibilities are as follows:

Engineering (Validation) Department

[][]To prepare the SOP & revise it when necessary.

Engineering (Maintenance) Department

[][]To provide necessary support for smooth operation & maintenance of the system.
[][]To ensure that the operators are responsible to carry out the operation and maintenance work and regular checking of the critical components and logbooks.
[][]To develop a list of spare parts based on the manufacturer’s recommendations and to forward the list to the Planning and Procurement department with a request to place order as required
[][]Engage technician/mechanic/operator/supplier in repair and maintenance work

Operators

[][]To operate the generator according to the SOP.
[][]To fill up the logbooks related to the Generator.
[][]To do the maintenance according to the check list.

Head of Engineering

[][]To ensure that the operation and maintenance of generator are done properly.
[][]To approve any maintenance/plans related to the generator.

Head of Quality Assurance

[][]To approve this SOP
[][]To ensure overall implementation of this SOP.

 

Procedure:

Precautions:

[][]All maintenance work must be carried out safely in accordance with the requirements of the Plant Safety Requirements and the EHS safety notices must be displayed around the plant. [][]Specific attention must be paid to the following:
[][]Personal protective equipment (PPE) and clothing appropriate to the job must be worn.
[][]Hearing protection must be used.

[][]Equipment must be electrically isolated and locked out where possible.
[][]Ensure the control panel is switched off before carrying out any check.
[][]Do not smoke when put fuel in the tank.
[][]Do not make adjustment that doesn’t understand.
[][]Do not remove the filler cap or any component of the cooling system while the engine is hot and while the coolant is under pressure, because dangerous hot coolant can be discharged.
[][]Maintenance activity must be carried out by trained technician/operators.
[][]“Under Maintenance” be displayed in a prominent position on a machine, equipment or facility undergoing maintenance work.

Engine Starting Procedure

Pre-Start Check

[][]Before the engine is started the operator should understand fully the reason for the controls and their use. The following check should be done before engine start.
[][]Check whether the Gas pressure is 10 psi or not.
[][]Make a general visual inspection on the engine and alternator. Check if there is any breakage, crack, leakage or looseness.
[][]Check the battery electrolyte level-fill with distilled water as necessary.
[][]Check that there is sufficient coolant level and if necessary, add the correct coolant.
[][]Check that there is sufficient lubricating oil in the sump & Viscosity and, if necessary add lubricating oil.
[][]Check the air filter and its connection.
[][]Check the all electrical connections are tight.
[][]Check the condition and tension of the fan end engine alternator belts-tighten as necessary.
[][]Check all hoses for loose connections or deterioration tighten or replace as necessary.
[][]Check the battery connection cables. Take care to tighten the loosened battery terminals with spanner and, cover with special substance and keep clean in order to avoid oxidation.
[][]Take out foreign materials such as keys, tools, cleaning wool, papers etc. on the engine and the Alternator.

Engine Start

[][]Reset the emergency stop.
[][]Press the reset button.
[][]Start key turn to the “ON” Position
[][]After start key turn to “ON” position following are checked:
[][]Check for any abnormal noise or vibration.
[][]Check for fluid leakage or leaks in the exhaust system.
[][]Check the control panel for indications of abnormal operations, particularly abnormally high temperature or low oil pressure. The oil pressure should be in the normal range within about 10 seconds of starting.
[][]Switch the alternator circuit breaker to “ON” (Handle Up).

Caution:

[][]Load can now be applied to the generating set (Normally 2-3 minutes wait from pressing the start button). The maximum step load can be 70%-100% of rated power depending on the generating set model. Typically we run 80% of rated load.
[][]Do not operate the engine at high speeds without a load.
[][]Do not overload the engine.

Engine Stopping Procedure

[][]Reduce the load gradually to the range of 0 – 50 kW.
[][]Turn off the load by switching output circuit breaker to “OFF” (Handle Down).
[][]Allow the generating set to run without load.
[][]After 2-3 minutes the key turn to the “OFF” position.
[][]In case of an emergency where immediate shutdown is necessary, the emergency stop push button should be pushed immediately without discounting the load.

Preventive Maintenance Planning

The preventive maintenance periods apply to average conditions of operation. The schedule which follows must be applied at the Interval (hours or months) which occur first.

Maintenance Interval with Maintenance action to be taken

Daily Maintenance

[][]Visually inspect engine, generator, transfer switch and Control panel.
[][]Clean the machine exterior and its surroundings.
[][]Ensure that the coolant is at the correct level.
[][]Check Oil, Water leaks.
[][]Check the amount of lubricating oil in the sump.
[][]Check the lubricating oil pressure at the panel display.
[][]Check the battery charge level.
[][]Check the air inlet filters.
[][]Drain air tank moisture and sediment.
[][]Inspect the engine fan blades.
[][]Inspect the drive belt.
[][]Check the intercooler and the coolant radiator for debris.
[][]Inspect and check the generator load and power factor.
[][]Check the voltage and frequency frequently

Weekly Maintenance

[][]Repeat Daily Check.
[][]Check Fuel lines and connections.
[][]Check for adequate fresh air to engine.
[][]Check hose and connections.
[][]Check battery charging alternator belts.
[][]Inspect the engine fan blades.
[][]Inspect the fan belt.
[][]Check oil level (Governor Housing).
[][]Check exhausts leakage.
[][]Tighten connections.
[][]Check Panel display.
[][]Tighten covers.
[][]Check output voltage and frequency.
[][]Inspect operation under load.
[][]Check for any unusual sounds.
[][]Terminals and connections normal color.
[][]Check if doors closed securely.

Monthly Maintenance

[][]Repeat weekly check.
[][]Clean the air filters.
[][]Check All fittings, Clamps, fasteners etc.
[][]Check generator air outlet.

After every 2500 Hours

[][]Tapped adjustment.
[][]Change lubricating oil.
[][]Change the lubricating oil filters.
[][]Change spin on filter.
[][]Change Air filter.

After every 16000 hours

[][]Change lubricating oil.
[][]Change the lubricating oil filters.
[][]Change spark plug cables.
[][]Clean/replace Gas filters and check/replace fuel hoses.
[][]Clean/replace air filter elements.
[][]Check for any leakage on engine, line and drains.
[][]Check crankcase venting valve and the crankcase pressure.
[][]Check/replace of all engine compensators.
[][]Check pumps and heat exchangers/radiator/cooling tower.
[][]Check engine starting battery, starting motor/starting system.
[][]Check/adjust valve clearances.
[][]Check engine safety controls, protection.

[][]Visually check turbocharger.
[][]Check push roads, cylinder head valve springs and valve heights.
[][]Check engine support, base rail level and anti-vibration pads
[][]Check air intake/exhaust system.
[][]Check engine governor.
[][]Check for any vibration or noise of engine
[][]Check cable termination.
[][]Check Genset control panel and instruments.
[][]Check performance and parameters of Genset during operation.

After every 32000 Hours

[][]Overhauling of engine
[][]Ensure that the turbocharger impeller and the turbocharger compressor casing are cleaned
[][]Ensure that the alternator, the starter and the turbocharger are checked
[][]Check the turbocharger bearing clearance.
[][]Check the exhaust restriction.
[][]Check the valves settings.
[][]Check, adjust and replace the ignition system spark plugs.
[][]Check vibration damper.
[][]Clean Turbocharger compressor wheel and diffuser.

After every 64000 Hours

Overhauling of full generator.
Ensure that the turbocharger impeller and the turbocharger compressor casing are cleaned.
Ensure that the alternator, the starter and the turbocharger are checked.

Annexure:

Annexure-I: Maintenance logbook of 1500 KW gas generator
Annexure-II: Log sheet for 1500 KW gas generator

Gas Generator Operation & Maintenance Read More »

Filter cleaning procedure with changing of process machines

Filter cleaning procedure, Purpose:

Filter cleaning procedure, The purpose of this SOP is to define the cleaning procedure of filters of various process machines of Production, Product Development and Warehouse departments.

Scope:

This Standard Operating Procedure applies to the fluid bed dryers, coating machines, dust collectors of tablet compression machine, laminar air flow unit, dispensing and sampling booths of production, product development and warehouse department which are located of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]FBD: Fluid Bed Dryer.
[][]HEPA: High Efficiency Particulate Air.
[][]EHS: Environment Health and Safety.
[][]PPE: Personal Protective Equipment.
[][]SOP: Standard Operating Procedure.
[][]W.C: Water column (pressure unit).
[][]PD: Product Development.
[][]PAO: Poly Alpha Olefin.

Responsibilities:

[][]The roles and responsibilities are as follows:

Engineering (Validation) Department

[][]Preparing the SOP and revise it when necessary.

Engineering (Maintenance) Department

[][]To provide necessary support to the technician for cleaning the filters.
[][]To check that the filters are properly cleaned/changed.
[][]To check that the log book is properly filled.

Technician

[][]To clean/change the filters when necessary.

Head of Engineering

[][]To ensure filters are cleaned/changed according to the SOP.

Head of Quality Assurance

[][]To approve the SOP.
[][]To ensure overall implementation of this SOP.

Procedure:

Precautions:

[][]All operational work must be done safely in accordance with the requirements of the Plant Safety Statement and the safety notices around the plant. Specific attention must be paid to the following:
[][]Use all Personal Protective Equipments such as goggles, masks, hand gloves etc. during cleaning/changing the filters.
[][]Disconnect the electrical power before opening the filters.
[][]Ensure all utilities before doing any kind of cleaning/changing task.

Cleaning and Changing procedure:

[][]Filters of FBD: There are five types of filters in FBD such as pre filter, medium filter, HEPA filter, product retaining filters and the cartridge filters of dust collector.
[][]To clean the cartridge filters and pre filters following procedures are followed:

Dismantle the filter from the filter housing.

[][]Clean the filters using compressed air at a pressure of 1-2 bar.
[][]Then take the filters to the filter cleaning area  and keep the filters drowning in the potable water for 2-3 hours.
[][]Then take out the filters from the water and partial drying is done by blowing compressed air at a pressure of 1-2 bar.
[][]After that, dry the filters under the sunlight.
[][]Finally, compressed air is used after sunlight to remove any dirt from the filters.
[][]Fix the filter into the filter housing.
[][]The pre filters are cleaned after every 15 days. An exchange is only required, if dirt is visible or any part of the filter is worn out.
[][]The cartridge filters are cleaned if the differential pressure is equal to or more than 4 in. of W.C. An exchange is only required, if dirt is visible or the differential pressure does not decrease after cleaning or any part of the filter is worn out.
[][]The medium filters and HEPA filters of inlet air handling unit are checked on every 3 months. Change the filters if the differential pressure is equal to or more than 4 in. of W.C.
[][]The product retaining filters are cleaned through production SOP.
[][]Filters of Coating machine: There are four types of filters in the coating machine such as: pre filter, medium filter, HEPA filter and cartridge filters of dust collector
[][]The cleaning procedure of pre filter and cartridge filter of dust collector is as same as it is described in the previous section The filters are cleaned after every 15 days. An exchange is only required, if dirt is visible or any part of the filter is worn out.
[][]An exchange of the filters is only required, if dirt is visible or the differential pressure does not decrease after cleaning or any part of the filters is worn out.
[][]The medium filter and HEPA filters of inlet air handling unit are checked every 3 months. Change the filters if the differential pressure is equal to or more than 4 in. of W.C.
[][]Filters of Dust Collector of Tablet Compression machine: They are cleaned using compressed air at a pressure of 1-2 bar after each batch of operation. Full cleaning (as per the procedure described in the previous section is done after 5 batches of operation.

Filters of Dispensing and Sampling Booth:

[][]There are pre filter, medium and HEPA filters in dispensing and sampling booths.
[][]The pre filters are cleaned on every month according to the procedure described in the previous section.
[][] The medium filters are cleaned using compressed air at a pressure of 1-2 bar when the differential pressure across the filter is equal to or more than 250 Pa.
[][]An exchange is only required, if dirt is visible or the differential pressure does not decrease after cleaning or any part of the filter is worn out.
[][]The HEPA filters are changed when the differential pressure across the filter is equal to or more than 400 Pa.

Filters of Laminar Air Flow unit of Dialysis Fluid area:

[][]There are two types of filters in the Laminar Air Flow unit such as: Pre filter and HEPA filter.
[][] The cleaning procedure of pre filter is as same as it is described in the previous section .
[][]The pre filter will be cleaned after every 15days.
[][]The HEPA filter will be checked on every month and will be changed if the differential pressure exceeds 250 Pa.
[][]An exchange is only required, if dirt is visible or any part of the filters is worn out.
[][]The filter integrity test (PAO test) of all the HEPA filters will be performed on every year.
[][]The filters will be changed in case of failure to meet the acceptance criteria of this test.
The technician will fill up the log books of filter cleaning/changing after cleaning or changing the filters.

Annexure:

Annexure – I: Log book of cleaning the filters of process machines
Annexure – II: Log book of changing the filters of process machines

Filter cleaning procedure with changing of process machines Read More »

Color Coding of Utility Lines

Color Coding, Purpose:

Color Coding, The purpose of this SOP is to define the color coding procedures of utility lines  of XX Pharmaceuticals Ltd.

Color Coding, Scope:

This SOP covers the color coding procedure of utility lines in Production, PD, QC and Microbiology area of of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]PW: Purified Water
[][]CA: Compressed Air
[][]WFI: Water For Injection
[][]Elec: Electric line
[][]PoW: Potable water
[][]HW: Hot potable water
[][]NT: Nitrogen line
[][]PD: Product Development
[][]CWFI: Cold Water For Injection

Engineering (Validation) Department

[][]Preparing the SOP and revise it when necessary.
[][]Identification of the utility lines with the assistance of Engineering persons.

Engineering (Maintenance)

[][]To put on the labels on respective utility lines.

Respective department

[][]To ensure that the labels are properly maintained.
[][]To inform the engineering department if any label is torn or harmed by any means.

Head of Engineering

[][]To ensure that all the utility lines are properly labeled.

Head of Quality Assurance

[][]To approve the SOP.
[][]To ensure overall implementation of this SOP.

Annexure:

N/A

Procedure:

Cleaning and Changing procedure:

[][]The list of utility lines which are to be marked is as follows:
[][]Purified water Potable water
[][]Cold Water For Injection
[][]Hot potable water
[][]Water for injection
[][]Compressed air Pure steam
[][]Nitrogen line
[][]Electric cable

The color coding procedure of each line is described below:

Purified water:

[][]All Purified Water lines must be tagged using an arrow head, Dark green colored tag. The length and width of the tag will be 18 cm and 3.0 cm respectively. “PURIFIED WATER” must be written in the middle of the tag and the font would be Cambria, bold, and black color on white background as well. The sample of the tag is shown below:

Potable Water:

[][]All Potable Water lines must be tagged using an arrow head, light green colored tag. The length and width of the tag will be 18 cm and 3.0 cm respectively. “POTABLE WATER” must be written in the middle of the tag and the font would be Cambria, bold and black color on white background as well.

Hot Potable Water:

[][]All Hot Potable Water lines must be tagged using an arrow head, light green colored tag and it will be surrounded by a red color band along its periphery. The length and width of the tag will be 18 cm and 3.0 cm respectively. “HOT POTABLE WATER” must be written in the middle of the tag and the font would be Cambria, bold black color on white background as well.

Water For Injection:

[][]All WFI lines must be tagged using an arrow head, dark green colored tag and it will be surrounded by a red color band along its periphery. The length and width of the tag will be 18 cm and 3.0 cm respectively. “WATER FOR INJECTION” must be written in the middle of the tag and the font would be Cambria, bold and black color on white background as well.

Compressed air:

[][]All Compressed Air lines must be tagged using an arrow head, dark blue colored tag. The length and width of the tag will be 18 cm and 3.0 cm respectively. “COMPRESSED AIR” must be written in the middle of the tag and the font would be Cambria, bold and black color on white background as well.

Pure Steam:

[][]All Pure Steam lines must be tagged using an arrow head, ash colored tag. The length and width of the tag will be 18 cm and 3.0 cm respectively. “PURE STEAM” must be written in the middle of the tag and the font would be Cambria, bold and black color on white background as well.

Nitrogen:

[][]All Nitrogen lines must be tagged using an arrow head, light blue colored tag. The length and width of the tag will be 18 cm and 3.0 cm respectively. “NITROGEN” must be written in the middle of the tag and the font would be Cambria, bold and black color on white background as well.

Electric line:

[][]All electric lines must be tagged using an arrow head, red colored tag. The length and width of the tag will be 18 cm and 3.0 cm respectively. “ELECTRIC CABLE” must be written in the middle of the tag and the font would be Cambria, bold and black color on white background as well.

Cold Water For Injection:

[][]All Cold Water For Injection lines must be tagged using an arrow head, dark green colored tag and it will be surrounded by a light blue color band along its periphery. The length and width of the tag will be 18 cm and 3.0 cm respectively. “WATER FOR INJECTION” must be written in the middle of the tag and the font would be Cambria, bold and black color on white background as well.

Chilled Water:

[][]All Chilled water lines must be tagged using an arrow head, blue colored tag. The length and width of the tag will be 18 cm and 3.0 cm respectively. “CHILLED WATER” must be written in the middle of the tag and the font would be Cambria, bold and black color on white background as well.

Pure Steam condensate:

[][]All Pure Steam condensate lines must be tagged using an arrow head, dark green colored tag and it will be surrounded by a yellow color band along its periphery. The length and width of the tag will be 18 cm and 3.0 cm respectively. “PURE STEAM CONDENSATE” must be written in the middle of the tag and the font would be Cambria, bold and black color on white background as well.

[][]All the tags will be put on the utility lines by the respective engineer.
[][]The tag will be maintained properly by the respective departmental persons. If the tag is torn or harmed by any means, the engineering department must be informed to replace it.

Color Coding of Utility Lines Read More »

AC Store Room Operation and Maintenance

AC Store Room, Purpose:

AC Store Room, The purpose of this SOP is to define the standard operating and maintenance procedure of AC store room in order to ensure its smooth & trouble-free operation.

AC Store Room, Scope:

This Standard Operating Procedure applies to the AC store rooms  of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]AC: Air Conditioner.

Responsibilities:

[][]The roles and responsibilities are as follows:

Engineering (Validation) Department

[][]Preparing the SOP and revise it when necessary.

Engineering (Maintenance) Department

[][]To provide necessary support for smooth operation & maintenance of AC  room.
[][]To ensure that the operators are responsible to carry out the operation and maintenance work and regular checking of the critical components and logbooks.
[][]To develop a list of spare parts based on the manufacturer’s recommendations and to forward the list to the Planning and Procurement department with a request to place order as required.

Operators

[][]To operate the AC room according to the SOP.
[][]To do the maintenance according to the check list and fill up the maintenance log book.

Manager, Engineering

[][]To ensure that the operation and maintenance of air compressor are done properly.
[][]To approve any maintenance/plans related to the compressor.

Manager, Quality Assurance

[][]To ensure overall implementation of this SOP.

Procedure:

Precautions:

[][]All operation and maintenance work must be done safely in accordance with the requirements of the Plant Safety Statement and the safety notices around the plant. Specific attention must be paid to the following:
[][]Use personal protective equipment before doing any kind of maintenance.
[][]Persons switching on the machines shall take adequate precautions to ensure that there is no one doing any kind of maintenance of machine.
[][]Switch off the power before doing maintenance.

[][]Keep the door shut while the AC is running.

System Description:

[][]There are two split type AC in the AC store room to maintain the desired temperature. The capacity of each AC is 2.5 ton. Each cooling unit consists of one indoor unit and one out door unit. The operation of AC is remote controlled. The desired temperature is set using the remote.
[][]Two ACs do not run at a time. While one runs another one stands by.

Operating Procedure:

[][]Starting of AC of AC store room:
[][]Insert the plug of AC into the power socket and switch ON the power.
[][]Press the button on the remote to switch ON the AC.
[][]Set the desired temperature by pressing up and down arrow key.
[][]Select the AUTO or COOL mode by pressing the button.

During Operation:

[][]During operation the temperature of AC store room is controlled automatically in automatic mode.
[][]The AC of AC store room is kept running 24 hrs. When one AC runs another one stands by.

Stopping procedure:

[][]Press button to switch OFF the AC.
[][]Unplug the plug from the power socket.

Maintenance Program:

Monthly Maintenance

[][]Check the current consumption of Compressor.
[][]Clean the filter.
[][]Clean the evaporator coil by blower.
[][]Clean the outdoor unit.
[][]Check and clean the blower.
[][]Check the refrigerant pressure. The pressure should be 50 – 60 psi. If the gas pressure is lower, recharge with new refrigerant.
[][]Check for any icing over the evaporator coil.

Half yearly Maintenance

[][]Overhauling of the whole machine.

Annexure:

Annexure I Equipment Use Log Book
Annexure – II: Maintenance of AC store room

AC Store Room Operation and Maintenance Read More »

Cold Room Operation & Maintenance

Cold Room, Purpose:

Cold Room, The purpose of this SOP is to define the standard operation and maintenance procedure of Cold room in order to ensure its smooth & trouble-free operation.

Cold Room, Scope:

This Standard Operating Procedure applies to the Cold rooms which are located at General and Cephalosporin Block.

Definitions / Abbreviation:

[][]N/A.

Responsibilities:

[][]The roles and responsibilities are as follows:

Engineering (Validation) Department

[][]Preparing the SOP and revise it when necessary.

Engineering (Maintenance) Department

[][]To provide necessary support for smooth operation & maintenance of cold room.
[][]To ensure that the operators are responsible to carry out the operation and maintenance work and regular checking of the critical components and logbooks.
[][]To develop a list of spare parts based on the manufacturer’s recommendations and to forward the list to the Planning and Procurement department with a request to place order as required.

Operators

[][]To operate the cold room according to the SOP.
[][]To do the maintenance according to the check list and fill up the maintenance log book.

Head of Engineering

[][]To ensure that the operation and maintenance of air compressor are done properly.
[][]To approve any maintenance/plans related to the compressor.

Manager, Quality Assurance

[][]To ensure overall implementation of this SOP.

Procedure:

 Precautions:

[][]All operation and maintenance work must be done safely in accordance with the requirements of the Plant Safety Statement and the safety notices around the plant. Specific attention must be paid to the following:
[][]Use personal protective equipment before doing any kind of maintenance.
[][]Persons switching on the machines shall take adequate precautions to ensure that there is no one checking or working on the control panel of the machine.
[][]Keep the door shut during operation.

System Description:

[][]The Cold room of both Cephalosporin and General Block has been manufactured by Frigair.
[][]The raw materials are stored in the room at a temperature of 2 – 8 ⁰C. There is a split type AC of capacity 5 ton to maintain the temperature.
[][]The indoor unit contains evaporator, blower etc.
[][] The outdoor unit contains compressor, condenser, oil separator, filter dryer etc. There is a data logger to monitor the temperature of cold room for 24 hrs.

Operating Procedure:

Starting of Cold room:

[][]Switch ON the main switch. The Yellow and blue indicator will be ON.
[][]Then switch ON the blower by turning the switch to ON position. The blue indicator light will be ON.
[][]After 5 minutes compressor will be ON automatically. The BLUE indicating light will be ON.
[][]To set the required lower temperature, press the SET button. Then press up and down arrow button to set the required temperature.
[][] The temperature band is programmed as 5.5⁰C i.e if the lower temperature is set at 2.5 ⁰C, the higher temperature will be automatically set at 8.0⁰C.

During Operation:

[][]During operation check for any alarm. If the compressor and blower trip then the trip light will be ON and buzzer will give alarm.
[][]If the temperature of cold room becomes very much lower, the CC Heater will be ON and compressor will be OFF.
[][]In that case, the CC heater indicating light will be ON.
[][]In case of icing, the compressor, blower will be OFF and CC heater will be ON. The Defrost indicating light will be ON.
[][]Check the temperature in the display of monitor.
[][]Check the data logger. Change the page once a week because one page is used for a week.

Stopping procedure:

[][]Switch off the compressor by turning the switch to OFF position. The indicating light will be OFF.
[][]Then switch off the blower by turning the switch to OFF position. The indicating light will be OFF.
[][]Switch off the main switch. The Yellow and Blue indicating light will be OFF.

Maintenance Interval/ Maintenance action to be taken

Daily Maintenance

>>Check for any alarm.
>>Check whether all the equipments operate sequentially.

Weekly Maintenance

>>Clean the outdoor unit.
>>Clean the blower.
>>Clean the drain pan of indoor unit.

Monthly Maintenance

>>Check the refrigerant pressure.
>>The pressure should be 50 – 60 psi.
>>If the gas pressure is lower, recharge with new refrigerant.

Annexure:

Annexure I Equipment Use Log Book
Annexure – II: Maintenance log book of Cold room

Cold Room Operation & Maintenance Read More »

Thermal Validation System Operation Procedure

Thermal Validation System, Purpose:

Thermal Validation System, The purpose of this SOP is to define the Operation of Thermal Validation system situated at Calibration Lab of XX Pharmaceuticals Ltd.

Thermal Validation System, Scope:

This SOP covers the operating procedure of Thermal Validation System manufactured by Anville Instruments Ltd., UK and located at Calibration Lab of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]Pre-calibration: Calibration of thermocouples before performing any qualification.
[][]Post-calibration/Calibration check: Calibration Check of thermocouples after performing any qualification.
[][]USB: Universal Serial Bus.

Responsibilities:

[][]The roles and responsibilities are as follows:

Validation Department

[][]Preparing the SOP and revise it when necessary.

Head of Engineering

[][]To ensure the proper operation of the system following the SOP.

Head Quality Assurance

[][]To approve the SOP.
[][]To ensure overall implementation of this SOP.

Procedure:

Precautions:

[][]Do not touch the thermocouples with bare hands as it might create itching on the skin due to having glass wool insulation.
Do not touch the thermal bath, thermocouples and reference temperature probe with bare hand when working under high temperature.
[][]Ensure that the thermocouples are properly inserted in the thermal bath due to having no erroneous readings while performing pre and post-calibration.
[][]When the thermocouples are inserted or affixed inside the autoclave or Depyrogenation Tunnel, be careful that these do not get stuck with anything. This is because, thermocouples might be torn apart.

System Description:

[][]The thermal validation system is comprised of following components:
[][]Data Logger: This 18 (16 temperature and 02 pressure) channels data logger of model Series 825 is manufactured by Anville Instruments Ltd., UK.
[][]Reference Temperature Probe: This probe, having model no. P750 is manufactured by Dostmann Electronic, Germany, which is used to perform the pre and post-calibration of thermocouples.
[][]Thermal Bath: The thermal bath of model TECAL 425F has been manufactured by TECHNE which is used as a source of temperature while performing the pre-calibration and post-calibration.
[][]Reference Pressure Calibrator: The reference pressure calibrator is used for pre and post-calibration of pressure transducer used in qualification of Autoclave.

[][]Thermocouples and pressure transducer: There are total 16 nos. T type thermocouples which are used to perform any kind of thermal validation.
[][]TQ Software: The software of version 6.1.2 and license number 2265486119 is used to interface the Data logger, Reference Temperature probe, thermocouples as well as pressure transducer. There is a dongle which holds the license for the software.
[][]Laptop: The laptop is used to operate all the components using TQ software.

Operating Procedure:

[][]There are mainly three steps involved in performing any thermal validation using this system such as pre-calibration, qualification as well as post-calibration/calibration check. All of these steps are described below:
[][]Pre-calibration of thermocouples and pressure transducer: All components must be connected to the laptop using USB port. Then, start the TQ soft by double clicking the TQSOFT icon. After that, following screen will be displayed:

[][]Click the Setup and enter electronic ID and password and the specific persons will be logged in the software.

[][]Click the ‘Logger’ option and choose “Calibration”. After that, following screen will be shown:

[][]Enter any suitable Job Ref in the respective box and press OK.

[][]Insert three different temperature values for calibration covering the operating range during validation. For instance, for autoclave validation set the Low point, High point and check point at 900C, 1300C and 121.10C respectively.

Set other parameters as follows:

[][]Stability 0.20C per minute for 3 minutes.
[][]Allowed deviation from reference 0.80C
[][]Reference stability criteria 0.020C for 01 minute.
[][]Report after stability for 1 minute.
[][]Report interval 20 secs.
[][]Report maximum deviation allowed 0.50C
[][]Then press OK and following screen will appear:
[][]Set the temperature of Thermal bath at low point and wait till all the probes are stabled. The “Countdown on Stability Requirements” will be zero for both thermocouples and reference probe when the readings are stable.
[][]Complete the Calibration by pressing “Proceed” and repeating the procedure for High and Check points.

Annexure:
Annexure I Equipment Use Log Book

Thermal Validation System Operation Procedure Read More »

Trimming Machine Operation & Cleaning Procedure

Trimming Machine, Purpose :

Trimming Machine, The purpose of this SOP is to describe the operation procedure of Trimming Machine in order to comply with cGMP standard.

Trimming Machine, Scope :

The scope of the procedure is applicable to the Trimming machine at the Dialysis Fluid Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]Trimming machine is a precision machine. It is covered by metal body. This machine consisting of a lever-operated knife and adjustable guides for container surfaces true to required angle.

Operator/Supervisor

[][]Operation and cleaning of the Trimming machine

Executive/ Sr. Executive

[][]Checking and ensuring that the operation and cleaning is performed according to the SOP.
[][]Preparation and timely review of the SOP.

Manager Engineering

[][]Preparation of maintenance schedule and maintenance of the machine.

Manager, Quality Assurance

[][]Ensure that the SOP reflects actual operation, cleaning and maintenance procedure.
[][]Approve the SOP against XX Pharmaceuticals Ltd. Master documents and current regulatory requirements.
[][]Implementation of the SOP.

Procedure :

Precaution(s) :

[][]Ensure that no unauthorized person gains operational access to the machine.
[][]Care must be taken to ensure that the drive units and accessory parts cannot be switched on inadvertently after servicing or maintenance work.

Instruction :

[][]Use Air (1 to 1.5 bar) during operation of Trimming machine.
[][]Keep the machine dry and cool environment.
[][]Keep the air pipe free from any other instrument, naught and coiling during operation and after completion of job.

Machine Assembling :

[][]Setting of in air pipe line of the machine.
[][]Ensure that the air pipe locks are tightly locked and cleaned.

Machine Operation :

[][]Check the machine that there is no abnormal setting of pipe in the machine.
[][]Connect the main electric supply with the socket.
[][]“On” the electric power.
[][]Then “On” the machine control power.
[][]After completion of assembling
[][]Placed the well required position of HPDE Container.
[][]Machine lever-operate HPDE container up the adjustable knife.
[][]Then Knife cutting the container mouth surfaces true to required.

Machine Dismantling :

[][]First “OFF” the air line valve and then remove the pipe from the source and the machine.
[][]“OFF” the machine control power.
[][]Then “OFF” the electric power.
[][]Remove the main power supply form the socket.

Machine cleaning :

Remove dusts from the machine with a dry lint free cloth.
Clean all the machine parts (air pipe and metal parts) with dry lint free cloth.

Annexure:

Annexure I Equipment Use Log Book

Trimming Machine Operation & Cleaning Procedure Read More »

Filter Integrity Test Machine Operation & Cleaning Procedure

Filter Integrity Test Machine, Purpose :

Filter Integrity Test Machine, The purpose of this SOP is to describe the operation and sanitization procedure of filter integrity test Machine in order to comply with cGMP standard.

Filter Integrity Test Machine, Scope :

The scope of the procedure is applicable to the filter integrity test machine at the DFU Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]Filter integrity test machine is a high precision machine. It is covered by special sealing profile with metal body, large size (10 inch) of touch PLC windows. This machine is associated with data control unit with networking system. BPT/ DFT/BDT are loaded into the machine by Supplier.

Responsibilities:

[][]The roles and responsibilities are as follows:

Operator/Supervisor

[][]Operation and cleaning of the filter integrity test machine
[][]Maintaining operation and cleaning log book.

Executive, Production

[][]Checking and ensuring that the operation and cleaning is performed according to the SOP.
[][]Checking the log book.
[][]Preparation and timely review of the SOP.

Manager Engineering

[][]Preparation of maintenance schedule and maintenance of the machine.

Head of Quality Assurance

[][]Ensure that the SOP reflects actual operation, cleaning and maintenance procedure.
[][]Approve the SOP against XX Pharmaceuticals Ltd. Master documents and current regulatory requirements.
[][]Implementation of the SOP.

Procedure:

Precaution(s):

[][]Ensure that no unauthorized person gains operational access to the machine.
[][]Care must be taken to ensure that the drive units and accessory parts cannot be switched on inadvertently after servicing or maintenance work.
[][]The cover must be kept in close position during operation.

Instructions:

[][]Use Nitrogen (7 to 8 bar) during operation of filter integrity testing.
[][]Keep the machine dry and cool environment.
[][]Keep the nitrogen and other silicon pipe free from any other instrument, naught and coiling during operation and after completion of job.

Machine Assembling :

[][]Remove the SS cover of the Upper side of the machine.
[][]Setting of in and out pipe line of the machine.
[][]Ensure that the pipe locks are tightly locked and cleaned.

Machine Operation :

[][]Check the machine that there is no abnormal setting of pipe in the machine.
[][]Connect the main electric supply with the socket.
[][]Open the flap of automatic data controller (which is situated on the Upper side of the machine) & on the UPS switch.
[][]On the control power of automatic data controller.
[][]Login the password.
[][]After completion of assembling,
[][]Fix the recommended test method setting.
[][]Fix the pre-pressure on the nitrogen pressure gauge setting.
[][]Fix the main-nitrogen pressure setting.
[][]Log in by the main user.
[][]Select the “Program Test” on PLC.
[][]Press the “Page Down” on the PLC of machine.
[][]Select the “Test Technique” (Like: BPT, DFT, BDT).
[][]Press the “Page Down” On PLC of machine.
[][]Set the minimum and maximum range of nitrogen pressure (3000mbar to 4000mbar) as per recommendation of filter certificate.
[][]Press the “Page Down” on PLC machine.
[][]Then set the Product Name, Batch No., and Filter Identity No. on the PLC of machine.
[][]Press “Page Down” and press “Save” button.
[][]Then check all the pipe line again and plug on the nitrogen out line to the filter housing.
[][]Placed the well wetted (soaked by purified water) filter (02 micron) at “O” ring of the filter housing.
[][]Cover the filter housing and tightly locked with TC clam.
[][]After obtaining required steps lock the solution “In” line “OFF” with dead valve and TC clam tightly.
[][]Then press the “Start” button to start the filter integrity testing.
[][]During operation if we want to change (increase/decrease) any parameter or batch no. we have to Press “Stop” button and then put the data again.

Machine Dismantling :

[][]First “OFF” the nitrogen line valve and then remove the pipe from the source and the machine.
[][]Remove the nitrogen line from the filter housing.
[][]Press the “Main Menu” on the PLC of the machine.
[][]Remove the main power supply form the socket.

Machine cleaning :

[][]Remove dusts from the PLC of the machine with a dry lint free cloth.
[][]Clean all the machine parts (silicon pipe and metal parts) with dry lint free cloth.

Annexure:

Annexure I Equipment Use Log Book

Filter Integrity Test Machine Operation & Cleaning Procedure Read More »

Laminar Air Flow Machine Operation, Cleaning & Maintenance

Laminar Air Flow Machine, Purpose :

Laminar Air Flow Machine, The purpose of this SOP is to describe the operation, calibration and cleaning of Laminar Air Flow used for the Filling Area in the Dialysis Fluid unit (DFU) at XX Pharmaceuticals Ltd.

Laminar Air Flow Machine, Scope :

This procedure describes the application of Laminar Air Flow, for the Filling Area of formulated drug product at the XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]LAF: Laminar Air Flow

Responsibilities:

[][]The roles and responsibility is as follows:

Executive, Production

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Manager, Production

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.
[][]Schedule calibration of the instrument at the defined intervals.

Head of Quality Assurance

[][]Approval of the SOP.

Procedure:

Precaution(s):

[][]Ensure the Safety Precaution.
[][]No Water Contact on the switch Board.

Operation

[][]Ensure that all surface area is clean with PVC curtain.
[][]Check the Electric line ON
[][]Ensure that the Laminar Air Flow is cleaned on the day use.
[][]Plug on the electric line. .
[][]Switch on the power its main.
[][]Power on the Laminar Air Flow Light
[][]Switch ON the LAF operation.
[][]Check Pressure Gauge Meter.
[][]Ensure the Reading of air Differential Pressure 150pa-200pa.
[][]Record the Operational data in the Operation Logbook of Laminar Air Flow as per Annexure – II.
[][]Power off the Laminar Air Flow.
[][]Switch off the power from its main.

Cleaning and maintenance:

[][]Clean the outside case of the Laminar Air Flow using a mild detergent or disinfectant (e.g.75% IPA) if required.
[][]Clean the area around the Laminar Air Flow and wipe immediately. Special care should be exercised when cleaning up IPA 75% (usually).
[][]When required, clean all wires and contacts to avoid corrosion.
[][]Inspect the cables of the LAF for any signs of broken insulation.
[][]Inspect the Light Shade Dry Cleaned Cloth.
[][]Rinse through with Purified Water of PVC Curtain.
[][]Make sure that no water Flow to the HEPA Filter, Light Shade.

Annexure:

Annexure I Equipment Use Log Book
Annexure-II: Logbook for daily Operation of Laminar Air Flow.

Laminar Air Flow Machine Operation, Cleaning & Maintenance Read More »

SUPAC Guideline, Scale Up and Post Approval Changes

SUPAC Guideline Purpose

SUPAC Guideline, This guideline provide recommendation mainly to those sponsors of 1.0 New Drug Applications (NDA’s), 2.0 Abbreviated New Drug Applications (ANDA’S), And 3.0 Abbreviated Antibiotic Applications (AADA’s) who want to change during the post approval period

1.0 The components or composition;
2.0 The site of manufacture of an immediate release oral formulation.
3.0 Scale-up/scale-down of manufacture; and/or(Batch Size Change)
4.0 Manufacturing (Process and Equipment)

This guidance (SUPAC Guideline) has been deprived or resulted from the workshop on scale-up of immediate  release drug products directed by AAPS(American Association of Pharmaceutical Scientists) in conjunction with the USPC (United States Pharmacopoeial Convention) and FDA (Drug Administration).

SUPAC Guideline mainly focused on

[][]Levels of change,
[][]Each level of change for recommended chemistry, manufacturing, and controls tests
[][]In vivo bioequivalence tests/or in vitro dissolution tests,
[][]Documentation that should support the changes.

SUPAC Guideline doesn’t comment if compliance/inspection documentation doesn’t affected. Except as specified in this guideline, no post approval changes are affected. These guidelines do not comment on or affect compliance/verification documents issued by the CDER Compliance Office or the FDA Regulatory Authority.

Some useful definitions for SUPAC Guideline

Batch

A certain amount of drug or other ingredient is produced according to a of production order and during the same production cycle, it is intended to maintain consistent character & quality within certain limits.

Dissolution Testing

[][]Case A:
Dissolve Q = 85% in 900 mL (mL) for 15 minutes use of 0.1N Hydrochloride (HCl), USA Pharmacopoeia (USP) <711> Apparatus 1 at 100 rpm or Apparatus 2 at 50 rpm.

[][]Case B:
The multipoint dissolution profile in the application/summary interval is 15, 30, 45, 60, 120 minutes or until the asymptote is reached for the proposed and now accepted formula.

[][]Case C:
Water, 0.1N HCl, And pH 4.5, 6.5 and 7.5 USP buffers (5 separate Profile) Proposed and currently accepted pharmaceutical formulation where Multi-point dissolution profiles performed. Proper sampling should be done in the following locations: Up to 90% of the drug 15, 30, 45, 60 and 120 minutes Resolved from medicines or asymptote Reached. Surfactants can be used with suitable agents Justification.

Validation

Establishing a high level of security with documented evidence Producing a product that consistently meets that requirement for a particular process Given specifications and quality features. Verified the manufacturing process is a process that has been proven to carry out what it claims to be or is represented as. Proof of verification is obtained by If possible, process-based data collection and evaluation from the development phase to the production phase. Verification inevitably involves process certification ( Not only materials, equipment, systems, buildings, personnel) Includes control over the entire process of repeated batches or executions.

1.0 Components and Composition

This section of the guidance focuses on changing pharmaceutical additives. Changes in the amount of active substance are not covered in this guideline. Ingredients or compositional changes that cause the addition of new additives or the removal of additives are defined at Level 3 (defined below), except as described below.

SUPAC Guideline: Levels of change

Level 1 Change

Level 1 changes are unlikely to have detectable impact on product quality and performance.

Level 1 Change, Example

[][]Example 1

Removal or partial removal of an element intended to affect the color or odor of the drug product, Or change printing ink material on another approved material.

Example 2

[][]Changes in excipients, expressed as a percentage of (w/w) Total composition below the next percentage area:
[][]The above mentioned percentage has been demonstrated that the drug substance has been formulated to 100% of label/potency.
[][]Total additive shall not be more than 5%( If a product formulated with Active Ingredient I, Microcrystalline cellulose, lactose, magnesium stearate. Then Microcrystalline cellulose, lactose total quantity shall not be more than 5%.
[][]If any component increases 2.5%, other component shall be decrease at 2.5%; if we increase microcrystalline cellulose 2.5% then Lactose shall be decrease to 2.5% & this is vice versa which is relating to target dosage weight.
[][]Mentioned active and excipients in the formulation shall be multiple targets as it represents the nominal composition for the drug product where any future changes shall be in the dug product based. Based on approved composition allowable changes shall be made.

List of documents required to implement the Level 1 change

Chemistry Documentation
[][]Application / official release requirements and Stability Testing Report.
-Stability test: batch containing long-term stability data Reported in the annual report for one batch

[][]Dissolution Documentation
-Nothing goes beyond the application/official requirements.

[][]n Vivo Bioequivalence Documentation
-None/Nothing else.

[][]Filing Documentation
-Annual report (all information including data on long-term stability).

Level 2 Change

[][]Level 2 changes are changes that can have a significant impact on the quality and performance of the formulation. List of documentation depends on three factors for level 2 documentation. Therapeutic range, solubility and permeability. The range of treatment is defined as narrow or not narrow.

[][]Change in the excipient technical grade (i. e. Avicel PH102 vs. Avicel PH200.)
[][]Excipients changes has been demonstrated as w/w for the respective formulation which is greater than the Level I changes but it shall be equal to or less than the mentioned range demonstrated below.

Table 2: Level 2 Change

[][]The above mentioned percentage has been demonstrated that the drug substance has been formulated to 100% of label/potency.

[][]Total additive shall not be more than 10%( If a product formulated with Active Ingredient I, Microcrystalline cellulose, lactose, magnesium stearate. Then Microcrystalline cellulose, lactose total quantity shall not be more than 10%.

[][]If any component increases 5%, other component shall be decrease at 5%; if we increase microcrystalline cellulose 5% then Lactose shall be decrease to 5% & this is vice versa which is relating to target dosage weight.

List of documents required to implement the Level 2 change

Chemistry Documentation
[][]Application/ official release requirements and batch records.
[][]Stability testing: 1 lot with 3 months accelerated stability data and 1 lot for long-term stability data
[][]Dissolution Documentation
Case A, Case B & Case C required for 1.0 High Permeability, High Solubility Drugs, 2.0 Low Permeability, High Solubility Drugs, 3.0 High Permeability, Low Solubility Drugs.

[][]In Vivo Bioequivalence Documentation
-If the situation is not as described See Case A, Case B, or Case C, the refer to Level 3 Changes.

[][]Filing Documentation
Pre-approval supplement (accelerated stability data with all information) Annual report (long term stability data)

Level 3 Changes

Level 3 changes are those that are likely to have a significant impact on formulation quality and performance. Tests and filing documentation vary depending on the following three factors: Solubility, Permeability and therapeutic range.

Examples: Level 3 Changes

[][]Changes of excipient quantity for a narrow therapeutic drug over the above mentioned Table 1.
[][]Changes of excipient quantity of all drugs beyond those listed in Section Table 2.
[][]Changes of excipient quantity for low solubility, low permeability drug over the above mentioned Table 1.

List of documents required to implement the Level change

Chemistry Documentation

[][]Application/ official release requirements and batch records.
>>Stability test: One batch 3 month accelerated stability data & One batch long-term stability data Reported in one year report.
[][]Dissolution Documentation
>>Case B dissolution profile
[][]In Vivo Bioequivalence Documentation
>>Can be waived with the accepted verified in vivo/in vitro study.
[][]Filing Documentation
>>Pre-approval supplement (accelerated stability data with all information) Annual report (Long term stability data).

2.0 Site Changes

Changes in the site which is owned by company or site of contact manufacturing . No scale up batches, changes in component or composition batch shall not be mentioned/ include here. Selected site shall be possessed cGMP.

Level 1 Changes

Definition of Level
This is really a site to site change where actually no basic changes are made only administrative information are changes all of the control parameter like SOP, Environment, Equipment’s, Facility etc. are same and manpower is fully experienced on the new site in a single facility.

Documentation

[][]Chemistry Documentation
>>No special requirements

[][]Dissolution Documentation
>>No special requirements

[][]In Vivo Bioequivalence Documentation
>>None.

[][]Filing Documentation
>>Only Annual report

Level 2 changes

In the adjacent city blocks where the same equipment’s, environment, SOP’s etc. are used & no change are made except administrative information and the location of the site.
[][]Test Documentation
>>Chemistry Documentation
>>New site Location and updated batch records.
>>Batch long-term stability data reported in annual report.
[][]Dissolution Documentation
>>Official Requirements only
[][]In Vivo Bioequivalence Documentation
>>No issue
[][]Filing Documentation
>>Annual report (long-term stability test data), Changes being effected supplement;

Level 3 changes

[][]Level 3 changes comprise of an adjustment of assembling site to an alternate grounds. An alternate grounds is characterized as one that isn’t on similar unique adjoining site or where the offices are not in contiguous city blocks.

[][]To qualify as Level 3 change, similar Equipment Setup, Environment circumstances SOP’s, and controls should be utilized in the assembling system at the new site, and no changes might be made to the Manufacturing batch records with the exception of regulatory data, area and language interpretation, where required.

Test Documentation

>>Chemistry Documentation
>>New site Location of & updated batch record.
>>Application/compendial release requirements.

Stability:

>>Stability test: One batch 3 month accelerated stability data & One batch long-term stability data Reported in one year report.

Dissolution Documentation

>>Case B: Multi-point dissolution profile ought to be achieved within the utility/compendial medium at 15, 30, 45, 60 and a hundred and twenty mins or till an asymptote is reached. The dissolution profile of the drug product on the contemporary and proposed site must be similar.

In Vivo Bioequivalence Documentation

None.

Filing Documentation

Annual report (long-term stability data).

Level 1 Changes

Change in batch size, as much as and which includes a thing of 10 times the scale of the pilot/biobatch, in which: 1) the system used to produce the take a look at batch is of the identical layout and working concepts; 2) the batch is manufactured in complete compliance with CGMP’s; and 3) the equal well known running processes (SOP’s) and controls, in addition to the same components and production tactics, are used on the take a look at batch and on the overall-scale production batch.

Test Documentation

[][]Chemistry Documentation
>>Similar or as of Application/compendial release requirements.
>>Notification for change & submission of updated batch records in annual report.
>>Long term stability reported in annual report (One batch)
[][]Dissolution Documentation
>>Similar as of application/compendial release requirements.
[][]In Vivo Bioequivalence
>>None.
[][]Filing Documentation
>>long-term stability data (Annual report).

3.0 Batch Size change

Level 1 Changes

Changes in batch length past a aspect of ten instances the scale of the pilot/biobatch, wherein: 1) the machine used to supply the take a look at batch is of the identical design and operating principles; 2) the batch is (are) produced in whole compliance with CGMP’S; and 3) the same SOP’s and controls as well as the identical formulation and manufacturing approaches are used at the take a look at batch and on the full-scale manufacturing batch.

Test Documentation
[][]Chemistry Documentation
>>Similar or as of Application/compendial release requirements.
>>Notification for change & submission of updated batch records in annual report.
>>Long term stability reported in annual report (One batch) & three months accelerated stability data for One batch
[][]Dissolution Documentation
>>Case B testing.
[][]In Vivo Bioequivalence
>>None.
[][]Filing Documentation
>>long-term stability data (Annual report).

4.0 Manufacturing

Manufacturing adjustments/Change might also affect each system used in the production process & the technique itself.

A. Equipment

Level 1 Changes

Definition of Change

This class includes: 1) alternate from non-automated or non-mechanical system to automatic or mechanical equipment to transport elements; and a couple of) trade to opportunity device of the identical layout and working ideas of the equal or of a distinct potential.

Test Documentation

[][]Chemistry Documentation
>>Similar or as of Application/compendial release requirements.
>>Notification for change & submission of updated batch records in annual report.
>>Long term stability reported in annual report (One batch)
[][]Dissolution Documentation
>>Similar as of application/compendial release requirements.
[][]In Vivo Bioequivalence Documentation
>>None.
[][]Filing Documentation
>>Long-term stability data (Annual report).

Level 2 Changes

[][]Definition of Level
>>Equipment Change to a different design & different operating principles.

[][]Test Documentation
[][]Chemistry Documentation
>>Similar or as of Application/compendial release requirements.
>>Notification of change and submission of updated batch records.
>>Long term stability reported in annual report (One batch) with 3 month accelerated stability data.
[][]Dissolution Documentation
>>Case C dissolution profile.
[][]In Vivo Bioequivalence Documentation
>>None.
[][]Filing Documentation
>>long-term stability data (annual report); Prior approval supplement with justification for change;

B. Process

Level 1 Changes

This class includes process adjustments along with adjustments consisting of blending instances and operating speeds within application/validation degrees.
Test Documentation
[][]Chemistry Documentation
Similar as of application/compendial release requirements.
[][]Dissolution Documentation
Similar as of application/compendial release requirements.
[][] In Vivo Bioequivalence Documentation
None.
[][]Filing Documentation
Annual report.

Level 2 Changes

Definition of Level
This category includes process changes including changes such as mixing times and operating speeds outside of application/validation ranges.
Test Documentation
[][]Chemistry Documentation
>>Similar as of Application/compendial release requirements.
>>Change notification & updated batch records to be submit.
>>Stability testing: Long-term stability for One batch.
[][]Dissolution Documentation
>>Case B Study: Dissolution profile.
[][]In Vivo Bioequivalence study
>>None.
[][]Filing Documentation
>>Long-term stability (Annual Report); Changes being affected supplement;

Level 3 Changes

Application/compendial release requirements.
Change Notification & updated batch records submission.
[][]Stability testing:
Significant body of data available:
three months accelerated stability data for One batch reported in supplement; long-term stability data reported in annual report for one batch.
[][]Dissolution Documentation
Case B dissolution profile.
[][]In Vivo Bioequivalence Documentation
May be waived if a suitable in vivo/in vitro correlation has been verified/established.
[][]Filing Documentation
Prior approval supplement with justification; long-term stability data (Annual report).

[][]In Vitro Dissolution
As per USP/NF Section<711>, to be conducted for 12 individual dosages.

In Vivo Bioequivalence Studies

In vivo bioequivalence study has been demonstrated as below. The actual design style may vary as it can be treated as an intended design guide for drug and dosage form.

[][]Objective:
The drug product which manufacture has been changed its rate and extent of absorption shall be compare.
[][]Design:
The study layout must be a single dose, two-treatment, two-period crossover with adequate washout period among the 2 phases of the study.
[][]Selection of Subjects:
The range of subjects enrolled inside the bioequivalence observe need to be decided statistically to account for the intrasubject variability and to satisfy the modern bioequivalence interval.

[][]Procedure:
>>Each subject should obtain the subsequent remedies:
Treatment 1: Product produced with the proposed change.
Treatment 2: Product produced prior to the proposed change.
>>Following an overnight speedy of at least 10 hours, subjects must get hold of both Treatments 1 or 2 above with 240 mL water. Food ought to now not be allowed until four hours after dosing. Water can be allowed after the primary hour. Subjects must be served standardized food beginning at 4 hours at some stage in the look at.
[][]Restrictions:
>>Prior to and at some stage in each observe section, water can be allowed ad libitum except for 1 hour before and after drug administration. The issue ought to be served standardized food and drinks at unique instances.

List of Narrow Therapeutic Range Drugs: SUPAC Guideline

[][]Aminophylline Tablets, ER Tablets
[][]Carbamazepine Tablets, Oral Suspension
[][]Clindamycin Hydrochloride Capsules
[][]Clonidine Hydrochloride Tablets
[][]Clonidine Transdermal Patches
[][]Dyphylline Tablets
[][]Disopyramide Phosphate Capsules, ER Capsules
[][]Ethinyl Estradiol/Progestin Oral Contraceptive Tablets
[][]Guanethidine Sulfate Tablets
[][]Isoetharine Mesylate Inhalation Aerosol
[][]Isoproterenol Sulfate Tablets
[][]Lithium Carbonate Capsules, Tablets, ER Tablets
[][]Metaproterenol Sulfate Tablets
[][]Minoxidil Tablets
[][]Oxtriphylline Tablets, DR Tablets, ER Tablets
[][]Phenytoin, Sodium Capsules (Prompt or Extended), Oral Suspension
[][]Prazosin Hydrochloride Capsules
[][]Primidone Tablets, Oral Suspension
[][]Procainamide Hydrochloride, Capsules, Tablets, ER Tablets
[][]Quinidine Sulfate Capsules, Tablets, ER Tablets
[][]Quinidine Gluconate Tablets, ER Tablets
[][]Theophylline Capsules, ER Capsules, Tablets, ER Tablets
[][]Valproic Acid Capsules, Syrup
[][]Divalproex, Sodium DR Capsules, DR Tablets
[][]Warfarin, Sodium Tablets

SUPAC Guideline, here by apply for the above mentioned & SUPAC Guideline shall be followed for the same.

SUPAC Guideline, Scale Up and Post Approval Changes Read More »

Container Washing and Handling System of Dialysis Fluid Unit

Purpose :

The purpose of this SOP is to describe the procedure of container Washing and Handling system of Dialysis Fluid Unit at XX Pharmaceuticals Ltd.

Scope :

This SOP is applicable for the Production and Primary Packaging of Dialysis Fluid Unit at XX Pharmaceuticals Limited.

Definition / Abbreviation :

[][]HDPE: High Density Polyethylene

Responsibilities :

[][]The Roles and Responsibilities are as follows :

Operator

[][]To ensure that this procedure is followed.

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Head of Quality Assurance

[][]To approve the SOP.

Precautions :

[][]Ensure the Proper Safety Instruction Are Followed.
[][]Ensure that the Supply the Water (Potable, Hot & Purified).

Empty Container Washing Procedure :

[][]Send the ERP Requisition to the ware house, then they Provide QC passed Containers from General Warehouse.
[][]Places the containers (50pcs) at the Plastic Pallet and transfer to the container washing room.
[][]Ensure that all utility lines like compressed air, electric line, potable water (hot & normal) and purified water are in attendance.
[][]Put off the stopper plug.
[][]Placed the container perpendicularly (3Pcs at a time) at the washing machine then flow the potable water for 30 sec (inner & outer elevation).
[][]Supply the hot water (50 to 60o) into the containers for 30 sec (inner & outer elevation).
[][]Concluding Supply of Purified water into the containers for 30 sec (inner & outer elevation).
[][]After that washed container staging at the cage trolley, then transfer to the filling room.
[][]Ensure that area cleaning activity is recorded in Cleaning Log book
[][]Check and ensure that Containers Cleaning activity is recorded in respective ‘Equipment log book’
[][]Ensure that all Containers are labeled as CLEANED.

Annexure

Annexure-I: HDPE Container (10 L) Washing Record.

Container Washing and Handling System of Dialysis Fluid Unit Read More »

Product Changeover of Dialysis Fluid Unit

Product Changeover, Purpose :

Product Changeover, To lay down the Procedure of Product Change Over to the Production and Packaging Area during Product to Product changeover and Batch to Batch Changeover for Dialysis Fluid Unit(DFU)

(DFU).

Product Changeover, Scope :

This SOP is applicable for the Concern Personnel of Production and Packaging of DFU Unit at XX Pharmaceuticals Limited.

Definition / Abbreviation :

N/A

Responsibilities :

[][]The roles and responsibilities are as follows :

Operator

[][]To follow the laid down procedure.

Laundry Man

[][]To provide cleaned garments.

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Head of Quality Assurance

[][]To approve the SOP.

Precautions :

[][]Ensure the proper safety instructions are followed.
[][]Ensure that no previous product is available in the area.

Product to Product Changeover :

[][]Ensure that, all utility lines like compressed air line, steam line, electrical fixtures, air inlet ducts, return air risers, potable water and purified water lines are cleaned and no visible traces of product are present.
[][]Ensure that Outer surface of machine, table, door, floor, walls and ceiling are cleaned.
[][]Ensure that Pre-mixing, Mixing, Storage, Filling Vessel to be clean with plenty of water (First time Potable Water Finally Purified water).
[][]Ensure that area cleaning activity is recorded in ‘Room Cleaning Log Book’
[][]Ensure that all equipments in the area are cleaned according to their respective SOPs and no traces of previous product are visible within the equipment.
[][]Check and ensure that equipment cleaning activity is recorded in respective ‘Equipment Log Book’
[][]Ensure that Span between equipment usage and cleaning is not more than seventy two hours.
[][]Ensure that Balances in the production area are cleaned and accuracy check is done before use.
[][]Ensure that production utensils like scoops, spatula, sieve stand, punch trolley, pallets, BMR table and tool boxes are cleaned as per procedure.
[][]Ensure that all equipments are labeled as ‘CLEANED’.
[][]Ensure that fresh set of gowns are issued to concerned operators.
[][]Ensure that proper environmental condition is maintained in the area and the records of the same are maintained in the specified formats.
[][]Ensure the correctness of Batch Manufacturing Record / Batch Packaging Record.

Batch to Batch Changeover :

[][]Ensure that previous batch material is removed from the production area.
[][]Ensure that all the equipment and their spares are cleaned according to their respective SOPs.
[][]Ensure that equipment cleaning activity is recorded in respective ‘Equipment Log Book’.

Annexure:

Annexure I Equipment Use Log Book

Product Changeover of Dialysis Fluid Unit Read More »

Material and Man Flow of Dialysis Fluid Production Area

Material and Man Flow, Purpose :

Material and Man Flow, To lay down the procedure of Material and Man Flow to the Production and Packaging Area for Dialysis Fluid .

Material and Man Flow, Scope :

This SOP is applicable for the Concern Personnel of Production and Packaging of Dialysis Fluid Unit(DFU) of the XX  Pharmaceuticals Limited.

Definition / Abbreviation:

[][]BOM = Bill of Material
[][]QAD = Quality Assurance Department
[][]DFU= Dialysis Fluid Unit

Responsibilities:

[][]The roles and responsibilities are as follows:

Operator

[][]To follow the laid down procedure.

Laundry Man

[][]To provide cleaned garments.

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Head of Quality Assurance

[][]To approve the SOP.

Annexure:

N/A

Precautions :

[][]Do not step on the floor with bare foot.
[][]Rub hands with Disinfectant Solution before entering into the Production Area.
[][]Jewelry, Wrist Watch, Finger Ring & Ear Ring is not allowed to Production Area.
[][]No food is allowed to Production Area.
[][]Shoe>Cover >Cap >Apron >Mask.
[][]After wearing company provided dress, stand in front of the mirror and confirm that, clothing is covering full arms and cap is covering all hairs according to the sample photos displayed.
[][]Proceed towards the DFU Unit.

MAN FLOW ( Starting from D Change ) :

[][]Before entering into the primary change room, Personnel should complete secondary change as per procedure.
[][]Enter into the Primary Change Room.
[][]Rub hands with Disinfectant Solution (70% Iso-Propyl Alcohol).
[][]Open the door of Corridor, turn left side and proceed to the Production as well as Container Washing Area of DFU.

MATERIALS FLOW ( Starting from Ware-House, Solid Block ) :

[][]Collect Materials from Cargo Lobby (less than 25 Kg) for dispensing at the Dispensing Booth (GPR009) of General Block.
[][]Ensure that, around 25 Kgs. in a single Bag / Pack transfers directly to the DF Unit Air-Lock.
[][]Ensure that, all the materials dispensed as per BOM are to be needed to transfer to the Manufacturing Area of the DFU.
[][]Liquid Material (Glacial Acidic Acid) is to be collected from the Flammable Storage Area.
[][]Filled Containers (10L) are to be transferred to the Secondary Packaging Area of General Block by using transfer trolley.
[][]The received Filled Containers (10L) are taken to the Packaging Conveyor for proper Wiping, Labeling and Packaging.
[][]Packed Products as a whole batch are to be taken to the Quarantine Area on Pallets for QA Release.
[][]After getting QA Release Slip, the Finished Goods (as a whole batch) are to be transferred to the Central Ware-House through the Warehouse of Solid Block.

Material and Man Flow of Dialysis Fluid Production Area Read More »

Filter Cleaning, Regeneration & Storage System

Filter Cleaning, Purpose :

Filter Cleaning, The purpose of this SOP is to describe the setting, operation and cleaning procedure of Cartridge filter in order to comply with cGMP standard.

Filter Cleaning, Scope :

The scope of the procedure is applicable to the Cartridge filter of  Dialysis Fluid  of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]CIP : Clean In Place

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Operation and cleaning of the cartridge filter.
[][]Maintaining Equipment Log Book.

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Head of Quality Assurance

[][]To approve the SOP.

Annexure:

N/A

Precautions :

[][]Hot purified water should be not more than 60oc.
[][]The wash-down valves are in closed position.
[][]Check for any leakage from discharge valve.

Filter Cleaning:

[][]Remove the Filter housing from the Vessel.
[][]Cleaning of filter Cartridge (1.2, 0.45 & 0.2 micron or 1.0, 0.6 & 0.2 micron).
[][]Clean the Cartridge filter (1.2, 0.45 & 0.2 micron or 1.0, 0.6 & 0.2 micron) with potable water.
[][]Soak the Cartridge filter in hot purified water and retain for 30 minutes.
[][]Wash the Cartridge filter 3 times with purified water.
[][]Allow the Cartridge filter to dry in wash bay.
[][]After drying take the Cartridge filter in a Clean poly bag and Stored in Closed ss Cabinet.
[][]After final cleaning affix the ‘CLEANED’ label.

Filter Cleaning, Regeneration & Storage System Read More »

Dialysis Fluid Filling Machine set up, operation and cleaning

Dialysis Fluid Filling Machine, Purpose :

Dialysis Fluid Filling Machine, The purpose of this SOP is to describe the setting, operation and cleaning procedure of filling machine in order to comply with cGMP standard.

Dialysis Fluid Filling Machine, Scope :

The scope of the procedure is applicable to the filling machine at the production area of dialysis Fluid unit of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]LAF = Laminar Air Flow.
[][]PVC = Polyvinyl Chloride.

Responsibilities :

[][]The roles and responsibilities are as follows:

Operator

[][]Operation and cleaning of the filling machine.
[][]Maintaining equipment log book.

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Head of Plant Operation

[][]To agree the laid down procedure.

Head of Quality Assurance

[][]To approve the SOP

Procedure :

Precautions :

[][]Use face mask, rubber gloves and protective clothing during filling operation.
[][]Turn ON LAF before filling operation.
[][]Connect electric line properly.
[][]Filling vessel valves are in open position.
[][]Check any leakage from discharge valve, silicon pipe and filling piston.

Machine Assembling :

[][]Clean the machine well with lint free cloth.
[][]Assemble the machine change parts and all the connections that are necessary for certain types of Operation.
[][]Attach tightly the silicon pipe (2’’) to the storage vessel (2000L).
[][]Attach tightly the solution transfer pipe (1½’’) to the dosing unit.
[][]Covert the filling machine by the PVC curtain.

Machine Operation:

[][]Lock the chamber lid cover of 200L vessel properly.
[][]Turn the transfer pump ON/OFF key to ON.
[][]Transfer 2000 L solution from storage vessel (2000 L) by opening the gate valve of storage vessel.
[][]This system is done by product filling end times.
[][]Turn the filling machine ON/OFF key to ON.
[][]Placed two containers under the dosing nozzle pipe
[][]Wait for two dosing rotation per container (5Liters/Stroke) then push OFF button.
[][]Look the actual filling volume of the containers.
[][]Push the OFF button of filling machine if container supplies insufficient or any other problems.
[][]Check the solution during filling by looking at the vision area of lid cover.
[][]Transfer or sample the solutions by opening the sampling port valve manually.
[][]Push the OFF button to stop the machine and plug out the main electric line to its main.
[][]Record the machine start time, end time and other parameters in the ‘Equipment Log Book’

Machine Dismantling :

[][]Turn the machine ON/ OFF key to OFF the machine.
[][]Remove the solution transfer pipe and filling pipe manually.
[][]Remove the lid cover and turn OFF the stirring.
[][]Remove the electric industrial plug.

Machine Cleaning :

[][]Clean the machine with lint free cloth to remove dust.
[][]Clean the inner elevation of the filling machine by using potable water.
[][]Clean the inner elevation of the filling machine by using hot water.
[][]Clean the inner elevation of the filling machine by using purified water through pipe.
[][]Clean the outer elevation of the filling machine with potable water by rubbing with a lint free cloth.
[][]Soak with a clean dried lint free cloth to remove the water from the filling machine.
[][]Clean all of the machine parts with potable water, hot water then purified water.
[][]Soak with a clean dried lint free cloth to remove the water from the machine parts.
[][]Affix the clean label on the filling machine as ‘CLEANED’.

Annexure:

Annexure I Equipment Use Log Book

Dialysis Fluid Filling Machine set up, operation and cleaning Read More »

Induction Sealing Machine Set Up, Operation & Cleaning

Induction Sealing Machine, Purpose :

Induction Sealing Machine, The purpose of this SOP is to describe the Set up, operation, and cleaning of Induction Sealing Machine (Model: IND-130HC ) in the Dialysis Fluid Unit  of XX Pharmaceuticals Limited.

Induction Sealing Machine, Scope :

This SOP is applicable for the Production and Primary Packaging of Dialysis Fluid Unit XX Pharmaceuticals Limited.

Definition / Abbreviation :

[][]SOP: Standard Operating Procedure.
[][]Induction Sealing: Non-contact method of eddy (electromagnetic current) heating to a metallic disk that accomplishes the hermetic sealing.

Responsibilities :

[][]The Roles and Responsibilities are as follows :

Operator

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Head of Quality Assurance

[][]To approve the Document.

Annexure

Annexure-I: Operation Logbook of Induction Sealing Machine ( Model: IND-130HC )

Precautions :

[][]Never unscrew the Sealing Head valves of the handle.
[][]Have the meter serviced only by the Mettler Toledo service.
[][]Any spillage should be wiped off immediately some solvents might cause corrosion of the housing.
[][]Avoid the following environment influences:
[][]Powerful vibrations

Operation:

[][]Ensure that working area is clean.
[][]Switch on the power its main.
[][]Power on the Sealing Machine.

Set the Sealing Temperature and Time.

[][]Check the Time 0.8 sec and temperature 250° c.
[][]Placed the Aluminium Sealing Foil top of the Container (Filing Mouth).
[][]Sealed the Cap (HDPE) With Aluminium Sealing Foil.
[][]For Induction Sealing, Press wait until a stable endpoint (0.8 sec) has been reached.
[][]Hear the “beep” sound.
[][]See the sign (Blue Light) at the Front side of the display.
[][]Put Off the Induction Sealer and then Transfer the Sealed Container.
[][]Collect the Filled Container For Next Sealing.
[][]Press OFF if any Emergency Problem Arises.
[][]Record the Sealing data in the Operation Logbook of Sealing Machine (Model: IND-130HC) as per Annexure-I.
[][]Power off the Sealing Machine.
[][]Switch off the power from its main.

Cleaning and maintenance:

[][]Wipe the Induction Sealing Machine with dry cloth.
[][]The Body of the instrument may attack by KDF Solution.
[][]Wipe away any spillage immediately.

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Pre-Mixing Vessel Set Up, Operation and Cleaning

Pre-Mixing Vessel, Purpose :

Pre-Mixing Vessel, The purpose of this SOP is to describe the setting, operation and cleaning procedure of Pre-mixing Vessel in order to comply with cGMP standard.

Pre-Mixing Vessel, Scope :

The scope of the procedure is applicable to the Vessels at the Production area of Kidney Dialysis Fluid (KDF) of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]CIP : Clean In Place

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Operation and cleaning of the Pre-mixing Vessel.
[][]Maintaining Equipment Log Book.

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Head of Quality Assurance

[][]To approve the SOP.

Procedure

Precautions :

[][]Chamber cover is properly locked.
[][]The wash-down valves are in closed position.
[][]Check for any leakage from discharge valve.
[][]Use face mask, rubber gloves and protective clothing during handling of materials.

Machine Assembling

[][]Clean the machine well.
[][]Assemble the machine change parts and all the connections that are necessary for certain types of operation.
[][]Attach the vacuum material transfer unit to the lid cover to transfer Liquid material automatically.
[][]Attach the solution transfer unit to the lid cover to transfer solution automatically by pressure.
[][]Attach the vision unit with clamp to the cover of chamber.

Machine Operation:

[][]Lock the chamber cover with chamber cover locking. Check for proper locking.
[][]Turn the machine ON/OFF key to ON. the machine is ON.
[][]Set the impeller Rotation Per Minute (RPM) and process time to desired value at the regulator at SETUP button (user can change the Impeller speed)
[][]Look the actual speed of the impeller.
[][]To off the impeller off button.
[][]To add solution or water open the chamber covers and then transfers the solution or water pneumatically.
[][]To stop the machine immediately, push the EMERGENCY button backward, machine will be stopped immediately.
[][]To check the solution during process OFF the impeller. Lift the lid cover manually and check.
[][]To Transfer or sample the solutions open the discharge valve manually.
[][]Transfer the solution through the Filter Housing control button (manual option is available).
[][]When discharge is complete push the CLOSED button to close the discharge valve.
[][]Transfer the Solution in product to Mixing Vessel (2000L).
[][]Push the OFF button to stop the Machine.

Machine Dismantling

[][]Turn the machine ON/ OFF key to off the machine.
[][]Remove the solution transfer unit.
[][]Remove the Lid Cover and Vision unit.
[][]Remove the Sample Collection unit.
[][]Remove the Filter housing from the Vessel.

Machine Cleaning

Cleaning of Vessel

[][]Fill the Vessel with Potable Water, the inner surface of the vessel well enough to washout the processing materials .Clean the outer surface of the vessel with rubbing & plenty of potable and purified water.
[][]Stir for 5-10 min after sufficient amount of potable water 500L being aggregated at the bottom.
[][]Rub with brush on the top and side walls of the vessel.
[][]Transfer the total wash water to the Manufacturing Vessel 2000L.
[][]Clean the wall and top with the hot potable water.
[][]Rub with brush on the top and side walls of the vessel again.
[][]Fill the Vessel with Purified Water and stir 15 min and then transfer to mixing vessel.
[][]Transfer the total wash water from 500L to the Vessel 2000L, 2000L drainage via filling machine.
[][]Rinse the wall and top of the vessel with hot potable water again.
[][]Clean the top and wall of the vessel with dry lint free cloth.
[][]Rinse the outer and inner wall of the vessel with IPA.
[][]Remove all water from the vessel and pipe line with Compressed air flow.
[][]After final cleaning affix the ‘CLEANED’ label.

Annexure:

N/A

Pre-Mixing Vessel Set Up, Operation and Cleaning Read More »

Domino A-Series A-220 GP Ink Jet Printer Operation

Domino, Purpose:

Domino, To lay down the procedure for operation of ink jet printer (Domino A-Series A-220 GP Printer) in order to comply with cGMP at the Packaging area.

Domino, Scope:

This SOP is applicable for the Packaging Area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows :

Operator

[][]To follow the laid down procedure

Executive, Packaging

[][]To monitor and check the procedure is followed

Manager, Production

[][]To implement this correctly

Head of Plant Operation

[][]To agreed this SOP

Head of Quality Assurance

[][]To approve the SOP

Procedure :

Precaution:

[][]The working person must follow the safety procedures of work.
[][]For any trouble put OFF the main switch first and protect Materials.
[][]Check electric connection and mechanical set up.

Machine Operation

[][]All Operations of machine are controlled by the following different keys/buttons. There are two types of buttons.
[][]Permanent buttons with fixed functions.
[][]Function buttons (soft keys) with functions that change.
[][]To Machine start –up from Power off, Press & hold the Power on/off button for 2 sec.
[][]The green indicator on the power button is lit.LED begins to flash
[][]The status bar at the top will display any faults if got.
[][]The Home screen will display. Icon will show at top right corner.
[][]Press & hold the Jet start/stop button for 2-3 sec.
[][]The green indicator on the start/stop button begins to flash.
[][]The status bar displays faults or jet starting.
[][]The start-up takes approximate 70 sec.
[][]The status indication shows “Start”
[][]The printer is now ready to print message. Icon will show up at top right corner.
[][]To Machine Shut-Down from ready to print or standby, Press the Power on/off button for 2 sec.
[][]The green indicators on the Jet start/stop button & power on/off button begins to flash
[][]A timer is shown on the bottom right screen & display

To write new message from the Home Screen:-

[][]Press the “Message” button.
[][]Press the “New” button.
[][]Enter a “Name” for the message & press “Enter”
[][]Ensure the “Message settings”.
[][]Press “Add field” button.
[][]Select “Text” by cursor button & press “Enter”.
[][]Press “Add field” for 2nd portion & select “User defined”.
[][]Write date or Numbers.
[][]Repeat same procedure for “New” & “Enter” lines.
[][]Once the message is complete, press “Enter”.
[][]Save this message & press “Enter” again to return to main screen.
[][]To print the messages press the “Start Print” button.

To edit message saved in the message store:-

[][]Press “Edit” button .Message settings are highlighted.
[][]Use the keyboard to select the parameters wish to change.”W” for width.
[][]Press “Next Field” one of the message fields will be highlighted
[][]If required press “Next Field” again until the required field is highlighted.
[][]Change the Field settings.
[][]Press the “Edit Text” button. The message text can then be edited.
[][]Press the “Enter” button to “Save as”.

To print Message from the Home screen :-

[][]Press the “Message button”
[][]Use the cursor buttons to move up & down to high light the message to be printed.
[][]Press the “Start Print”.

To Print adjust any print parameters:-

[][]Press “Print adjusts”. When pressed you will see the screen.
[][]Press the relative character to adjust the options.

To insert LOGO from Home Screen:-

[][]Press the “Message” button.
[][]Press the “New” button.
[][]Enter a “Name” for the new message & then press “Enter”.
[][]Set the “message settings” before selecting to the “Add field”
[][]Select “logo” from the “Field select” screen using the cursor buttons & press “Enter”.
[][]From the selection screen select the logo by using the up/down cursor buttons. When the required logo is displayed on the screen press “Enter”.
[][]The logo will now be displayed in message screen. Field settings can be changed at this point. Ensure the correct font size is selected on the message settings. Screen.
[][]Press “Enter” to save the message & then press “Enter” again to return to the store screen. Press “Start Print” to print the highlighted message & return to the Home page.

Annexure:

Annexure-I : Equipment log book

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Digital weighing balance operation, accuracy check & cleaning at packaging Area

Digital weighing balance , Purpose:

Digital weighing balance, To lay down the procedure for operation, accuracy check and cleaning of the weighing balances at the Packaging Area.

Digital weighing balance, Scope:

This SOP is applicable for 510 g weighing balance for weighing of materials at the Packaging Area of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

N/A

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]To follow the laid down procedure

Executive, Packaging

[][]To monitor and check the cleanliness of area

Manager, Production

[][]To implement this correctly

Head of Quality Assurance

[][]To approve the Document

Procedure:

Precaution:

[][]Do not pour liquids on the weighing platform.
[][]Do not use solvents to clean the platform.
[][]Ensure balance is clean before use, including its surrounding area.
[][]Check and ensure the due date of calibration before use.
[][]Check and ensure the level indicator of weighing balance is in the middle, if applicable.
[][]Use hand gloves to hold standard weights for function check and calibration.

Daily Performance Check :

[][]Plug in the power cord.
[][]Level the balance using leveling feet so that air bubble is centered within circle of level indicator.
[][]To turn the balance ON, short pressing the → O/T ← key.
[][]Wait a while so that the stability indicator [*] is displayed.
[][]Zero the balance by pressing the → O/T ← key.
[][]Press the 100 mg mass at the centre of the platform and record the value displayed in the daily balance check logbook.
[][]Press the 100 g mass at the centre of the platform and record the value displayed.
[][]Press the 200 g mass at the centre of the platform and record the value displayed.
[][]Print the results by pressing print ( ) button if necessary.
[][]Record the value of those weights in Log Book for Daily Accuracy Check (As per Form No.: SOP/ PRO/004/I).
[][]If any displayed value is out of acceptable limit, label the balance “DO Not Use” and inform the QA Executive for immediate calibration of the balance.
[][]Balance check must be performed every working day before starting operation.
[][]If the factory remains close for the day(s), put the comments in the remarks column against that day(s) at the day of factory resume.

Operation of 510 gm Balance of OHAUS :

[][]Empty container for Weighing:
[][]Press the zero button.
[][]Place an empty container on the scale platform.
[][]Press the Tare button.
[][]Fill the container with material to be weighed.
[][]The terminal will display the net weight and the NET cursor will light up. Allow the reading to be stable. Write down the reading.
[][]To clear a tare weight (with the scale in the net weight mode and a tare weight previously entered),press the Clear key (C)

Filled container for Weighing:

[][]Press the zero button.
[][]Place the material to be weighed on the scale platform.
[][]The terminal will display the net weight and the NET cursor will light up. Allow the reading to be stable. Write down the reading.
[][]Follow the Daily Accuracy Check

Acceptance Criteria:

[][]The observed weights should be within ± 0.1% of the certified standard weights.
[][]If the acceptance criteria are not satisfied, follow the procedure for Handling of out of calibration for instrument & equipment.

Calibration:

[][]Perform the calibration in every six months. Recalibration is required in the following cases :
[][]After any minor service has been done or replacement of parts.
[][]When the software or firmware has been upgraded or changed.
[][]If daily check fails.

Cleaning:

[][]Place the status label ‘TO BE CLEANED’ on the equipment.
[][]Switch off the balance and unplug from the socket.
[][]Remove all objects from the weighing platform of balance.
[][]Lift up and remove the weighing pan in such a way that there is no damage in weighing system.
[][]Clean the pan including underside using a piece of dry cloth. Use wet cloth and finally clean with disinfection solution
[][]Wipe the display, switch board and cables with dry cloth.
[][]Remove ‘TO BE CLEANED’ and affix ‘CLEANED’label on the equipment after approval from Quality Compliance.
[][]Record the cleaning parameters on the ‘Equipment Log Book’.

Annexure:

N/A

Digital weighing balance operation, accuracy check & cleaning at packaging Area Read More »

Excess Secondary Packaging materials transfer to Warehouse

Excess Secondary Packaging materials, Purpose:

Excess Secondary Packaging materials, To lay down the procedure for transfer of Un-used Secondary Packaging Materials to Ware-House.

Excess Secondary Packaging materials, Scope:

This SOP is applicable for the Packaging Area of XX Pharmaceuticals Limited.

Definition / Abbreviation:

[][]Secondary Packaging Material: That Packaging Material which contains the primary packed product and has the Printed Information.

Responsibilities:

[][]The Roles and Responsibilities are as follows :

Operator

[][]To follow the laid down procedure.

Executive, Packaging

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Manager, Quality assurance

[][]To approve the Document.

Annexure:

N/A.

Procedure:

Precaution:

[][]Only the fresh and un-used parts of Secondary Packaging Materials are to be returned to the Ware-House without any Defective.
[][]Returning of Unused Secondary Packaging Materials
[][]Responsible Person / Supervisor shall take necessary measures to return the un-used part of received Secondary Packaging Materials and Packaging Person shall ensure the return of all the Un-used Secondary Packaging Materials after completion of each Batch Packaging.
[][]Secondary Packaging Materials such as Spoon, Measuring Cup, Plastic Dropper, Sticker Label, Inner Cartons, Inserts, Shipper Cartons which are to be returned shall be counted.
[][]Executive, Packaging shall visually check and ensure that no overprinted Packaging Materials like Sticker Label, Inner Cartons, Shipper Cartons are to be returned to the Ware-House.
[][]Enter all the details like Product Name, Batch No., Batch size, Name of the Material, Material ID, Lab. Control No., Quantity to be Returned on the ‘Stock Return Note’
[][]Operator shall mention all details in Stock Return Note (SRN) and Executive, Packaging shall check all of them accordingly.
[][]The SRN shall have triplicate copy. All the copies shall be moved along with the physical stock to the Ware-House and Executive / In-charge, Ware-House shall return the rest of 02 (Two) copies to the Packaging after duly signed. One copy shall attach with Batch Packaging Record and another copy shall retain in the book as reference copy.

Excess Secondary Packaging materials transfer to Warehouse Read More »

Secondary Packaging materials receiving from ware-house

Secondary Packaging materials receiving , Purpose:

Secondary Packaging materials receiving , To lay down the procedure for Receiving of Batch Required Secondary Packaging Materials from Ware-House.

Secondary Packaging materials receiving , Scope:

This SOP is applicable for the Packaging Area of XX  Pharmaceuticals Limited.

Definition / Abbreviation:

[][]Secondary Packaging Material: Secondary packaging is outside the primary packaging, perhaps used to group primary packages together & giving the best possible protection for products on the way to retail.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]To follow the laid down procedure

Executive, Packaging

[][]To monitor and check the laid down procedure

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure:

Precaution:

[][]Check the Requisition carefully before sending to Ware-House.
[][]Prepared the Secondary Packaging Materials Requisition and sending it to the respective person of the Ware-House after taking approval from the Head of Production.
[][]After receiving the formal requisition from Packaging, In-Charge, Ware-House will check the latest stock position of the required items one by one.
[][]When present stock complies, then go for checking QA Passed stock one by one.
[][]As the Reel Type Packaging Items (e.g. Sticker Label) have the reasonable pack intact, and to be used pack-wise.
[][]When other Packaging Materials (Inner carton, Insert, Label, Cup, Dropper, Shipper carton, Cellulose tape) are available that time In-Charge, Ware-House will issue them and supply them on the basis of the materials requisition by the Ware-House Personnel to the Packaging Area.
[][]After complete delivery from the Ware-House, respective Packaging In-Charge / Supervisor will confirm their receipt of correct item(s) with quantity by signature. Update the ‘Material Issue Record’ register (Annexure-I).
[][]When the schedule batch(s) will consumption, then un-used and fresh part will be kept in their outer pack and send to the respective Ware-House.
[][]Ware-House Personnel keep the Secondary Packaging Materials at the designated Place(s) with sequential order.

Annexure:

Annexure I – Material Issue Record.

Secondary Packaging materials receiving from ware-house Read More »

Ink Jet Printer Set Up & Operation

Ink Jet Printer, Purpose:

Ink Jet Printer, To lay down the procedure for Operation,  in order to comply with cGMP at the Packaging area.

Ink Jet Printer, Scope:

This SOP is applicable for the Packaging Area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows :

Operator

[][]To follow the laid down procedure

Executive, Packaging

[][]To monitor and check the procedure is followed

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Machine Operation

[][]First check the machine physically.
[][]Connect the electrical cable.
[][]Switch ON the power supply.
[][]Enter Password on the PLC.
[][]Select Job form PLC as specified.
[][]Save the select file.
[][]Enter into the setting menu from PLC.
[][]Set and save the Machine parameter from PLC.
[][]Press Counter ON from PLC.
[][]Adjust the cartridge and sensor.
[][]Press PRINT button on the PLC.

Ink Jet Printer Set Up & Operation Read More »

Conveyor Belt Operation and Cleaning

Conveyor Belt , Purpose :

Conveyor Belt , The purpose of this SOP is to describe the operation and cleaning procedure of Conveyor Belt in order to comply with cGMP standard.

Conveyor Belt , Scope :

The scope of the procedure is applicable to the Conveyor Belt at the Packaging area of XX Pharmaceuticals Limited

Definitions / Abbreviation:

N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Operation and cleaning of the Conveyor Belt
[][]Maintaining Equipment Log Book

Executive, Packaging

[][]To monitor and check the laid down procedure

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Annexure:

N/A.

Procedure:
Precautions:

[][]For any troubles/disturbances, put off the main switch first and protect the materials.
[][]For any danger situation ring the bell.
[][]Assurance weekly, monthly and yearly servicing and maintenance in consultation with Engineering Department.

Machine Operation

[][]First Check the machine physically.
[][]Check electric connection and mechanical set up.
[][]Machine switch on.
[][]Light on and blower on.
[][]Open the door.
[][]After completion desired work clean the Laminar Unit properly.
[][]Close the door and switch off main switch.
[][]Check electric connection and mechanical set up.
[][]Check the machine for cleanliness & take cleaning clearance from Quality Compliance.
[][]Main switch ON.
[][]Run the machine.
[][]Machine speed is to be controlled by Inverter.
[][]After finishing the operation switch off machine & main switch.
[][]Record the machine start & end time and other parameters in the ‘Equipment Log Book’.

Machine Cleaning

Remove dusts from the machine body with a vacuum cleaner.
Clean all the machine parts with dry lint free cloth.
Clean the machine body, product contact parts, clamps and other machine parts with wet mop.
Remove the water with lint free cloth.
After final cleaning affix the ‘CLEANED’  label.
Record the cleaning parameters on the ‘Equipment Log Book’

Annexure: 

Annexure I Equipment Use Log Book

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Sticker labeling machine set up, operation & cleaning

Sticker labeling machine, Purpose:

Sticker labeling machine, The purpose of this SOP is to describe the Set up, Operation and Cleaning of Sticker labeling machine in order to comply with cGMP standard.

Sticker labeling machine, Scope:

This SOP is applicable for the Packaging Area of XX  Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Operation and cleaning of the Sticker labeling machine
[][]Maintaining Equipment Log Book.

Executive, Packaging

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Annexure:

N/A.

Procedure:
Precaution :

[][]Always turn OFF the machine before threading the label web through the machine.
[][]Keep hands away from moving machine parts while machine is in operation.

Machine Assembling

[][]Before operation assemble the machine accessories that are necessary for operation.
[][]Set the Batch no. Mfg date and Exp date on the hot stamp Printer.
[][]Set Label and carbon roll.

Machine Operation

[][]Connect the electrical cable and compressed air line.
[][]ON main power switch.
[][]Press ENTER on the PLC.
[][]Select mode form PLC as specified.
[][]Switch ON the turn table.
[][]Press Label ON from PLC.
[][]Press Print ON from PLC.
[][]Press counter ON from PLC.
[][]Adjust label on the label roll of the machine.
[][]Press RUN button on the PLC.
[][]Record the machine operation start time & end time and other parameters on the ‘Equipment Log Book’.

[][]Machine Dismantling

After operation disassemble the machine accessories.
Remove the hot stamp printer for changing Batch no. Mfg date and Exp date.

Machine Cleaning

[][]Remove dusts from the machine with a vacuum cleaner.
[][]Clean all the machine parts with dry lint free cloth then with wet mop.
[][]Swab the machine body and change parts with lint free cloth.
[][]After final cleaning affix the ‘CLEANED’ label.
[][]Record the cleaning parameters on the Equipment Log Book.

Sticker labeling machine set up, operation & cleaning Read More »

Digital Weighing Balance operation, accuracy check at packaging area

Digital Weighing Balance operation, Purpose:

Digital Weighing Balance operation, To lay down the procedure for operation, accuracy check and cleaning of the weighing balances at the Packaging Area.

Digital Weighing Balance operation, Scope:

This SOP is applicable for 820 gm weighing balance for weighing of materials at the Packaging Area of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:\

Operator

[][]To follow the laid down procedure

Executive, Packaging

[][]To monitor and check the cleanliness of area

Manager, Production

[][]To implement this correctly

Head of Quality Assurance

[][]To approve the Document

Annexure:

N/A

Procedure:
Precaution:

[][]Do not pour liquids on the weighing platform.
[][]Do not use solvents to clean the platform.
[][]Ensure balance is clean before use, including its surrounding area.
[][]Check and ensure the due date of calibration before use.
[][]Check and ensure the level indicator of weighing balance is in the middle, if applicable.
[][]Use hand gloves to hold standard weights for function check and calibration.

Daily Performance Check :

[][]Plug in the power cord.
[][]Level the balance using leveling feet so that air bubble is centered within circle of level indicator.
[][]To turn the balance ON, short pressing the → O/T ← key.
[][]Wait a while so that the stability indicator [*] is displayed.
[][]Zero the balance by pressing the → O/T ← key.
[][]Press the 100 mg mass at the centre of the platform and record the value displayed in the daily balance check logbook.
[][]Press the 100 g mass at the centre of the platform and record the value displayed.
[][]Press the 200 g mass at the centre of the platform and record the value displayed.
[][]Print the results by pressing print ( ) button if necessary.
[][]Record the value of those weights in Log Book for Daily Accuracy Check (As per Form No.: SOP/ PRO/004/I).
[][]If any displayed value is out of acceptable limit, label the balance “DO Not Use” and inform the QA Executive for immediate calibration of the balance.
[][]Balance check must be performed every working day before starting operation.
[][]If the factory remains close for the day(s), put the comments in the remarks column against that day(s) at the day of factory resume.

Operation of 820 g Balance of Mettler Toledo :

Empty container for Weighing:

[][]Press the zero button.
[][]Place an empty container on the scale platform.
[][]Press the Tare button.
[][]Fill the container with material to be weighed.
[][]The terminal will display the net weight and the NET cursor will light up. Allow the reading to be stable. Write down the reading.
[][]To clear a tare weight (with the scale in the net weight mode and a tare weight previously entered),press the Clear key (C)

Filled container for Weighing:

[][]Press the zero button.
[][]Place the material to be weighed on the scale platform.
[][]The terminal will display the net weight and the NET cursor will light up. Allow the reading to be stable. Write down the reading.
[][]Follow the Daily Accuracy Check.

Acceptance Criteria:

[][]The observed weights should be within ± 0.1% of the certified standard weights.
[][]If the acceptance criteria are not satisfied, follow the procedure for Handling of out of calibration for instrument & equipment.

Calibration:

[][]Perform the calibration in every six months. Recalibration is required in the following cases :
[][]After any minor service has been done or replacement of parts.
[][]When the software or firmware has been upgraded or changed.
[][]If daily check fails.

Cleaning:

[][]Place the status label ‘TO BE CLEANED’ on the equipment.
[][]Switch off the balance and unplug from the socket.
[][]Remove all objects from the weighing platform of balance.
[][]Lift up and remove the weighing pan in such a way that there is no damage in weighing system.
[][]Clean the pan including underside using a piece of dry cloth. Use wet cloth and finally clean with disinfection solution
[][]Wipe the display, switch board and cables with dry cloth.
[][]Remove ‘TO BE CLEANED’ and affix ‘CLEANED’  label on the equipment after approval from Quality Compliance.
[][]Record the cleaning parameters on the ‘Equipment Log Book’ .

Annexure:

Annexure I Equipment Use Log Book

Digital Weighing Balance operation, accuracy check at packaging area Read More »

Line Clearance at Packaging Area Procedure

Line Clearance , Purpose:

Line Clearance , To lay down the Procedure for Line Clearance at the Packaging Area.

Line Clearance , Scope:

This SOP is applicable for the Packaging Area of XX Pharmaceuticals Limited.

Definition / Abbreviation:

Line Clearance : Line Clearance is a method of assuring components, labels, and documents have been removed and accounted from the previous work order for before starting a new work order and to make certain the line is properly prepared for the next work order.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]To follow the laid down procedure

Executive, Packaging

[][]To monitor and check the laid down procedure

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure:

Precautions:

[][]Ensure the proper safety instructions are followed.
[][]Ensure that no previous product is available in the area.
[][]Line Clearance during Product to Product Changeover
[][]Clean all utility lines like compressed air line, air inlet ducts and return air risers with dry mop to remove loose dust from the floor.
[][]Clean the door, floor, walls and ceiling with dry cloth & finally wet mop.
[][]Area cleaning activity is recorded in ‘Room Cleaning Log book’
[][]Clean all equipment in the area according to their respective SOPs and no traces of previous product are visible within the equipment.
[][]Check and ensure that equipment cleaning activity is recorded in respective ‘Equipment Log Book’
[][]Ensure that Span between equipment usage and cleaning is not more than seventy two hours.
[][]Balances, if available in the packaging area, are cleaned and accuracy check is done before use.
[][]Fresh set of gowns are issued to concerned operators.
[][]Proper environmental condition is maintained in the area and the records of the same are maintained in the specified formats.
[][]Ensure the correctness of Batch Packaging Record.

Line Clearance during Batch to Batch Changeover

[][]Ensure that previous batch material is removed from the packaging area.
[][]Ensure that all equipment and their spares are cleaned according to their respective SOPs.
[][]Ensure that equipment cleaning activity is recorded in respective ‘Equipment Log Book’.
[][]Ensure that floor is cleaned using vacuum cleaner and no visible traces of the previous batch materials on the floor.
[][]Proper environmental condition is maintained in the area and the records of the same are maintained in the specified formats.
[][]Ensure the correctness of Batch Packaging Record.

Annexure:

Annexure I Equipment Use Log Book

Line Clearance at Packaging Area Procedure Read More »

Temperature and Relative Humidity Monitoring at Packaging Area

Temperature and Relative Humidity Monitoring, Purpose:

Temperature and Relative Humidity Monitoring, To lay down the procedure for monitoring of Temperature & Relative Humidity (%) at the Packaging area.

Temperature and Relative Humidity Monitoring, Scope:

This SOP is applicable for the Packaging Area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows :

Operator

[][]To follow the laid down procedure

Executive, Packaging

[][]To monitor and check the procedure is followed

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Annexure:

N/A.

Procedure :

Precaution :

[][]Do not use a new hygrometer unless it is calibrated.
[][]When any hygrometer is shifted from one location to another, allow to stabilize the device prior to record the temperature / Relative Humidity (%).
[][]Check the due date of calibration of the hygrometer and magnehelic gauge before taking reading.
[][]Ensure that temperature and Relative Humidity (%) readings are taken before going to operation.
[][]Temperature and Relative Humidity (%) (using Digital Hygrometer)
[][]Ensure that no dust is accumulated over the sensor.
[][]Read the temperature and relative humidity (%) values displayed on the screen of digital hygrometer and record.

Area

[][]Packing Hall, Waste, Cleaner’s, Printing, IPC Room, Office Executive and Packing Material Staging.

Temperature

[][]NMT 25°C

Relative Humidity (%)

[][]NMT 60 %

Frequency

[][]Twice in a shift, first before starting the operation and second after four hours.
[][]If the reading is not within limit at any time of operation, inform the Engineering department immediately.

Temperature and Relative Humidity Monitoring at Packaging Area Read More »

Packaging Area Cleaning Procedure

Packaging Area Cleaning, Purpose:

Packaging Area Cleaning, To lay down the procedure for effective cleaning at the Packaging Area.

Packaging Area Cleaning, Scope:

This SOP is applicable for the Packaging Area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]To follow the laid down procedure

Executive, Packaging

[][]To monitor and check the cleanliness of area

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure:

Precaution:

[][]Do not clean/disinfect the area when the packing is running.
[][]Keep the cleaning agents at the designated place only with proper labels.
[][]Ensure that after usage the wet mops are washed and hanged in hanger in cleaner store & allowed to dry. Ensure other cleaning tools are also hanged in hanger after use.
[][]After use of cleaning agent wash hands, feet and fingers thoroughly with soap & plenty of water.
[][]Ensure that during cleaning all the product containers are closed.
[][]Check and ensure that disinfectant solution prepared is not stored for use for the next day and the residue is discarded by pouring into drain.
[][]At least two different disinfectants are to be used alternatively on weekly basis..
[][]Do not mop the floor after keeping Cleaned equipment in clean equipment storage room.

Cleaning Tools / Agents

[][]Portable vacuum cleaner
[][]Cloth & wiper
[][]Potable water
[][]Glass Cleaning agent: ‘Clear View’ (Brand Name).
[][]Disinfectant (Savlon/ Dettol/ Chlotec).
[][]Floor cleaning agent Perfect 7/Enviro Care
[][]Preparation of 2.5 % v/v Chlorhexidine Gluconate Solution
[][]To make 10 L disinfectant solution take 2.5 L Chlorhexidine Gluconate in freshly collected purified water to make up volume up to 10 L).
[][]Stir well to mix the solution properly.
[][]Prepare the disinfectant solution separately in separate bucket for use in different floor.
[][]Maintain the ‘Disinfectant Solution Preparation Record’.

Product to Product Cleaning Procedure (Type-A Cleaning) for Secondary Packaging Area

[][]Type – A cleaning is defined as cleaning procedure followed during product to product changeover.
[][]If the unit/equipment is used for same product it has to be cleaned after 72 hours.
[][]Place the status label ‘TO BE CLEANED’  in the Area.
[][]Clean the ceiling, walls, light fixtures, supply diffusers (SD) and return grills (RG) first with portable
[][]Vacuum cleaner to remove loose dust using a platform trolley, then with wet mop.
[][]Clean the machine/Equipment in packaging are As per SOP.
[][]Clean the doors, windows, compressed air lines and other service lines with dry cloth and then wet mop.
[][]Clean the glasses with ‘Clear View’ solution and wipe.
[][]Clean the control panels, electrical wires with dry cloth.
[][]Clean toolbox, table, log books, SOP folders, hygrometer, stool / chair with dry Cloth.
[][]Clean the floor first with dry mop, then with Perfect 7/Enviro Care and finally with potable water.
[][]Ensure after inspection for absence of any residue of previous product. If any residue of previous product or extraneous matter is found, re-clean the area using above procedure until the area is free of any residue/ extraneous matter.

[][]Remove ‘TO BE CLEANED’ and affix ‘CLEANED’ label in the cleaned area.
[][]Record the cleaning activity in ‘Room Cleaning Log Book’.

Frequency of Cleaning

[][]During product to product change over.
[][]If 72 hours time exceeds after cleaning and the equipment or area is not used, use the equipment or area after performing B-type cleaning.

Batch to Batch Cleaning (Type-B Cleaning) for Secondary Packaging area

[][]Type – B cleaning is defined as cleaning procedure followed during batch to batch changeover of a particular product.
[][]Place the equipment status label ‘PARTIALLY CLEANED’  in the area.
[][]First Clean the floor, ceiling, walls, light fixtures, supply diffusers (SD), return grills (RG) doors, windows and equipment with portable vacuum cleaner to remove the loose dust. Finally clean the floor with wet mop.
[][]Remove ‘PARTIALLY CLEANED’ label and affix ‘CLEANED’ label in the area.
[][]Record the cleaning activity in ‘Room Cleaning Log Book’.

Frequency of Cleaning

[][]During batch to batch change over.

Cleaning at the End of Day’s Operation

[][]Clean external parts of the machine, and operating panel with dry cloth.
[][]Clean the floor first with dry mop and finally with disinfectant solution.
[][]Frequency of Cleaning
[][]At the end of the day’s work.

Packaging Area Cleaning Procedure Read More »

Transfer of Finished Goods to the Finished goods storage area

Transfer of Finished Goods, Purpose:

Transfer of Finished Goods, To lay down the procedure for to the Finished Goods Storage Area.

Transfer of Finished Goods, Scope:

This SOP is applicable for the Packaging Area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]N/A

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]To follow the laid down procedure

Executive, Packaging

[][]To monitor and check the laid down procedure

Manager, Production

[][]To implement this correctly

Head of Quality Assurance

[][]To approve the Document

Annexure:

Annexure I – Finished Goods Transfer Note.
Annexure II – Weight Checking Record of Inner Carton
Annexure III – Weight Checking Record of Shipper Carton

Procedure:

Precautions:

[][]Do not transfer finished goods to the Finished Goods Storage area without Quality Compliance (QCOM) approval.
[][]Warehouse personnel should not receive finished goods from Production without any ‘Finished Goods Transfer Note’.
[][]Ensure that proper labels are on shipper carton & pallet.
[][]Check the weight of individual inner carton and keep record at 30 minutes interval in Annexure-II (Weight Checking Record of Inner Carton).
[][]Attach the Transparent Hologram Sticker on inner carton.
[][]Place the inner cartons in shipper carton and seal the shipper carton using gum tape.
[][]Check and ensure that ‘PRODUCT LABEL’  of shipper carton (Product name, Batch No., Mfg. Date, Exp. Date, Pack Quantity, Sr. No., Packed by, Storage Condition) is legible and clear.
[][]Check the weight of individual shipper carton and keep record of every shipper carton’s weight in Annexure-III (Weight Checking Record of Shipper Carton).
[][]Seal on every shipper carton as the following using rubber stamp (L-3.25 inch X W-2.0 inch) and record the relevant information which corresponds with Annexure-III.

SHIPPER CARTON NO.:………………….

WEIGHT:……………………………………….

NAME:…………………………………………..

SIGNATURE AND DATE:……………….

[][]Keep the shipper cartons on a clean pallet. Use more than one pallet if required to keep shipper cartons on it.
[][]In case of Loose shipper carton affix ‘LOOSE LABEL’  on two sides of shipper carton (Front & Back).
[][]Prepare a ‘Finished Goods Transfer Note’ after completion of packing of a batch as per format (Annexure – I).
[][]QCOM shall affix ‘QUARANTINED’ label on pallet.
[][]When the batch is approved by Quality Compliance (QCOM), hand over the batch along with Finished Goods Transfer Note to warehouse personnel.
[][]Maintain batch details in ‘Finished Goods Register’ Production personnel will sign as ‘Transferred by’ and warehouse personnel as ‘Received by’ in the Finished Goods Register.

Annexure:

Annexure I – Finished Goods Transfer Note.
Annexure II – Weight Checking Record of Inner Carton
Annexure III – Weight Checking Record of Shipper Carton

Transfer of Finished Goods to the Finished goods storage area Read More »

Material Drying Machine Set Up, Operation & Cleaning

Material Drying Machine , Purpose :

Material Drying Machine , The purpose of this SOP is to describe the setting, operation and cleaning procedure of Material Drying Machine (Model: Standard) in order to comply with cGMP standard.

Material Drying Machine , Scope :

The scope of the procedure is applicable to the Material Drying Machine (Model: Standard) at the Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Sep Up, Operation and cleaning of the Material Drying Machine (Model: Standard)
[][]Maintaining Equipment Log Book

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure

Precautions :

[][]Make sure that the main power switch is OFF position before and after operation.
[][]Use face mask, rubber gloves and protective clothing during handling of materials.
[][]Check the cleanliness of individual tray and machines inner part during assembling of machine.
[][]Booth side doors are in lock position during operation.
[][]Check the air outlet damper position before and after completion of operation.

Machine Assembling

[][]Keep the necessary change parts near the material dryer machine before assembling.
[][]Assemble the dryer by opening the front side door of the dryer.
[][]Load the tray with material and place into the tray holding rack.
[][]Then set the rack carrying trolley.
[][]Then place the tray holding rack into the machine.
[][]After that closed the door accurately with the help of door locking handle.
[][]Then closed the air outlet damper and tight the screw accurately.

Machine Operation

[][]Switch ON the main power switch.
[][]Open the plastic cover and set the desire temperature of the machine.
[][]Then open the plastic cover and set the desire time of the machine.
[][]At first switch ON the blower of the machine.
[][]Then switch ON the heater of the machine.
[][]After completed the drying time open the air outlet damper for material cooling and check the LOD.
[][]After operation switch OFF the heater and then blower. Unload the tray holding rack from the machine.
[][]Finally switch OFF the main power of the machine.
[][]Record the machine operation parameters in the ‘Equipment Log Book’.

Machine Dismantling

[][]Open the both side door of the machine.
[][]Unload the tray holding rack from the machine with the help of carrying trolley.
[][]Remove the tray from the rack.

Machine Cleaning

[][]Remove dusts from the machine body and other necessary parts with a vacuum cleaner.
[][]Clean all the machine parts with dry lint free cloth.
[][]Use potable water to clean the machine body, product contact parts, tray and other machine parts.
[][]Use hot water to clean all the trays.
[][]Finally rinse the machine body, product contact parts, trays and other machine parts with purified water.
[][]Remove the water with lint free cloth.
[][]After final cleaning affix the ‘CLEANED’ label.
[][]Record the cleaning parameters in the ‘Equipment Log Book’.

Annexure:

Annexure I Equipment Use Log Book

Material Drying Machine Set Up, Operation & Cleaning Read More »

Material Pulverization Machine Set Up, Operation & Cleaning

Material Pulverization Machine, Purpose :

Material Pulverization Machine, The purpose of this SOP is to describe the setting, operation and cleaning procedure of the Material Pulverization Machine (Model: 30B) in order to comply with cGMP standard.

Material Pulverization Machine, Scope :

The scope of the procedure is applicable to the Material Pulverization Machine (Model: 30B) at the Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Sep Up, Operation and cleaning of the Material Pulverization Machine (Model: 30B)
[][]Maintaining Equipment Log Book

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Manager, Quality Assurance

[][]To approve the Document.

Procedure
Precautions :

[][]Make sure that the main power switch is OFF position before and after operation.
[][]Use face mask, rubber gloves and protective clothing during handling of materials.
[][]Check the cleanliness of sieves, ss container, tray and gasket before assembling of machine.
[][]Check the sieve for its integrity before and after completion of operation.

Machine Assembling

[][]Keep the necessary change parts near the machine before assembling.
[][]Assemble the machine by opening the front side cover of the machine.
[][]Adjust the sieve into the ring with the help of screw.
[][]Then set the sieve ring into the machine.
[][]Close the cover of the machine properly.
[][]Set the filter bag of the machine with the help of spring and clamp.
[][]Place the tray under the filter bag.

Machine Operation

[][]Switch ON the main power switch.
[][]Switch ON the blower by pressing green button of the machine.
[][]Then switch ON the motor by pressing green button of the machine.
[][]Input the material through the hopper of the machine manually.
[][]Sieve the material and collect sieved material through the cover discharge opening.
[][]After operation first switch OFF the motor then switch OFF the blower by pressing red button.
[][]Record the machine operation parameters in the ‘Equipment Log Book’.

Machine Dismantling

[][]Open the front cover of the machine.
[][]Remove the sieve ring of the machine.
[][]Remove the filter bag of the machine.
[][]Remove the tray of the machine.

Machine Cleaning

[][]Remove dusts from the machine body and other necessary parts with a vacuum cleaner.
[][]Clean all the machine parts with dry lint free cloth.
[][]Use potable water to clean the machine body, product contact parts, tray, container, sieve & filter bag.
[][]Use hot water to clean all the product contact parts such as sieve ring.
[][]Finally rinse the machine body, product contact parts, trays and other machine parts with purified water.
[][]Remove the water with lint free cloth.
[][]After final cleaning affix the ‘CLEANED’ label.
[][]Record the cleaning parameters in the ‘Equipment Log Book’.

Annexure:

Annexure I Equipment Use Log Book

Material Pulverization Machine Set Up, Operation & Cleaning Read More »

Bottle Drying Machine Set Up, Operation & Cleaning

Bottle Drying Machine, Purpose :

Bottle Drying Machine, The purpose of this SOP is to describe the setting, operation and cleaning procedure of the Glass Bottle Drying Machine (Model: Standard) in order to comply with cGMP standard.

Bottle Drying Machine, Scope :

The scope of the procedure is applicable to the Glass Bottle Drying Machine (Model: Standard) at the Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Sep Up, Operation and cleaning of the Glass Bottle Drying Machine (Model: Standard)
[][]Maintaining Equipment Log Book

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure
Precautions :

[][]Make sure that the main power switch is OFF position before and after operation.
[][]Use face mask, rubber gloves and protective clothing during handling of materials.
[][]Check the cleanliness of individual tray and machines inner part during assembling of machine.
[][]Booth side doors are in lock position during operation.
[][]Check the air outlet damper position before and after completion of operation.

Machine Assembling

[][]Keep the necessary change parts near the material dryer machine before assembling.
[][]Assemble the dryer by opening the front side door of the dryer.
[][]Load tray with glass bottle and place into the tray holding rack.
[][]Then set the rack carrying trolley.
[][]Then place the tray holding rack into the machine.
[][]After that closed the door accurately with the help of door locking handle.
[][]Then closed the air outlet damper and tight the screw accurately.

Machine Operation

[][]Switch ON the main power switch.
[][]Open the plastic cover and set the desire temperature of the machine.
[][]Then open the plastic cover and set the desire time of the machine.
[][]At first switch ON the blower of the machine.
[][]Then switch ON the heater of the machine.
[][]After completed the drying time open the air outlet damper for bottle cooling and check the bottle.
[][]After operation switch OFF the heater and then blower. Unload the tray holding rack from the machine.
[][]Finally switch OFF the main power of the machine.
[][]Record the machine operation parameters in the ‘Equipment Log Book’.

Machine Dismantling

Open the both side door of the machine.
Unload the tray holding rack from the machine with the help of carrying trolley.
Remove the tray from the rack.

Machine Cleaning

Clean all the machine parts with dry lint free cloth.
Use potable water to clean the machine body, product contact parts, tray and other machine parts.
Use hot water to clean all the trays.
Finally rinse the machine body, product contact parts, trays and other machine parts with purified water.
Remove the water with lint free cloth.
After final cleaning affix the ‘CLEANED’ label.
Record the cleaning parameters in the ‘Equipment Log Book’.

Annexure:

Annexure I Equipment Use Log Book

Bottle Drying Machine Set Up, Operation & Cleaning Read More »

Bottle Washing Machine Set Up, Operation And Cleaning

Bottle Washing Machine, Purpose :

Bottle Washing Machine, The purpose of this SOP is to describe the setting, operation and cleaning procedure of Glass Bottle Washing Machine (Model: IRW-16) in order to comply with cGMP standard.

Bottle Washing Machine, Scope :

The scope of the procedure is applicable to the Glass Bottle Washing Machine (Model: IRW-16) at the Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Set up, operation and cleaning of the Washing Machine (Model: IRW-16)
[][]Maintaining Equipment Log Book

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure

Precautions :

[][]Make sure that the main power switch is OFF position before and after operation.
[][]Use face mask, rubber gloves and protective clothing during handling of materials.
[][]Check the cleanliness of individual water reserve tank and machines inner part during assembling of machine.
[][]Do not touch the hot water tank during operation.
[][]Check the individual bottle washing nozzle working properly.

Machine Assembling

[][]Keep the necessary change parts near the bottle washing machine before assembling.
[][]Assemble the washing machine by bottle holder.
[][]Load the pump 1 with tap water and pump 2 with hot water.
[][]Load the bottle holder with glass bottle.
[][]Set the nozzle’s spray rate of tap water and purified water depending on the glass bottle size.

Machine Operation

[][]Switch ON the main power switch.
[][]Switch ON the heater switch of the machine and wait 20 minutes for hot water (60ºC).
[][]Then press the START button of the main motor.
[][]After press the START button of the pump 1.
[][]Then press the START button of the pump 2.
[][]Open the valve of compressed air line.
[][]After completing the glass bottle washing procedure close the valve of tap water, purified water & compressed air line.
[][]After operation switch OFF the heater, pump 2, pump 1 and then main motor.
[][]Finally switch OFF the main power of the machine.
[][]Record the machine operation parameters in the ‘Equipment Log Book’.

Machine Dismantling

[][]Open the cover of the machine.
[][]Remove the bottle holder of the machine.
[][]Drainage the water of pump 1 & pump 2.

Machine Cleaning

[][]Remove dusts from the machine body and other necessary parts with a vacuum cleaner.
[][]Use potable water to clean the machine body, product contact parts and other machine parts.
[][]Use hot water to clean all the parts.
[][]Finally rinse the machine body, product contact parts and other machine parts with purified water.
[][]Remove the water with lint free cloth.
[][]After final cleaning affix the ‘CLEANED’  label.
[][]Record the cleaning parameters in the ‘Equipment Log Book’.

Annexure:

Annexure I Equipment Use Log Book

Bottle Washing Machine Set Up, Operation And Cleaning Read More »

Blister Packaging Machine Set Up, Operation & Cleaning

Blister Packaging Machine, Purpose :

Blister Packaging Machine, The purpose of this SOP is to describe the setting, operation and cleaning procedure of the Blister Packaging Machine (Model: HM-V3) in order to comply with cGMP standard.

Blister Packaging Machine, Scope :

The scope of the procedure is applicable to the Blister Packaging Machine (Model: HM-V3) at the Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Set Up, Operation and cleaning of the Blister Packaging Machine (Model: HM-V3)
[][]Maintaining Equipment Log Book

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Manager, Quality Assurance

[][]To approve the Document.

Annexure:

N/A.

Procedure

Precautions :

Safety

[][]Never run the machine with its door open.
[][]Use face mask, rubber gloves and protective clothing during handling of materials.
[][]Keep the switches “OFF” during break-time and at the end of the job.
[][]Care must be taken to ensure that the drive units and accessory parts cannot be switched on inadvertently after servicing or maintenance work.

Special Instruction

[][]Be sure that the power switches are “OFF” position.
[][]Beware of the high temperature of “Sealing top mold” during cleaning and if possible, allow it to cool down completely.
[][]Should not use methanol or other organic solvent like ethanol, carbon tetrachloride, thinner, benzene etc. to clean plastic doors and other parts of the machine.
[][]Water should not be used to clean metal parts of the machine.
[][]Care should be taken to ensure that no water enters inside the motor.
[][]Corrosive materials should not be used to clean the machine.
[][]Heavy parts should not dismantle alone, always taken help from others.
[][]Machine chiller purified water level should be check fifteen days interval and purified water should be change every three months interval.
[][]Carefulness should be taken about heavy parts handling.

Machine Assembling

[][]Switch on the main power supply of the machine.
[][]Check the draw in of the base film and the lid foil.
[][]Check Compressed air valve open and air pressure above 6 bars.
[][]Turn control panel key “ON”.
[][]Push reset button and press main button.
[][]Press setup button to show password for entering product list.
[][]Select Specific product from product list and press main button.
[][]Adjust draw off length by pressing inching switch according to advance length.
[][]Check the emergency push buttons, safety switches of the safety guards/glass doors.
[][]Press Main button and enter into information and positioning the machine according to following parameter-
[][]Forming station
[][]Sealing station
[][]Embossing
[][]Cooling station
[][]Perforation / Slitting station.

[][]Set following change parts by push inching switch-
Forming
Perforation / Slitting
Cutter
[][]Set following change parts carefully-
Pre-heating
Guide rail
Sealing upper-lower plate.
Embossing
Cooling Plate
Pulling Station
Feeding Tray

[][]Push reset button and checks the machine accurately by inch the inching switch press.
[][]Set bottom foil & lid foil and cutting shall be adjusted by inching switch on manual mode with press-
Heater.
Chiller.
Draw off.
Sealing lift.
[][]Press “Start” button and run machine to check the pocket forming and batch code embossing.
[][]Insert tablets or capsules on the pocket of PVDC/PVC/ALU film on the guide rail and perform a leak test operation of those strips to ensure proper sealing.
[][]Press manual mode and “OFF” all button only the following button shall “ON”
Heater.
Chiller and
Sealing lift.
[][]Convert manual mode to auto mode for running the machine.
[][]After completed the all parts setting, check that every parts are setting properly & proper place.
[][]Ensure that every screw nuts are tight properly.
[][]Set batch code with the respective digit.
[][]Emboss batch code and show Quality Assurance Officer for approval.

Machine Operation

[][]Ensure that area and equipment are clean and suitable to start the operation.
[][]Before starting the blister machine use surgical gloves, nose mask etc.
[][]Set different change parts like forming plate, sealing plate, code embossing, guid rail, cooling plate etc. in proper position.
[][]Set the top Foil (Alu foil) & Bottom Foil (PVC, PVDC & Alu foil) correctly.
[][]Open the compressed air valve & ensure that the air pressure is above 6 bars. Check & ensure that the compressed air is free from moisture.

[][]Temperature for PVDC preheating 110-140ºc and sealing 150-180ºc and for slitting are 60-80ºc & embossing Alu 70-80 ºc, temperature for Alu sealing 160-180 ºc and embossing 70-90 ºc maintained .
[][]Tablets and Capsules are placed manually to the PVDC forming or Alu forming pocked. Different packs are produced for different products by forming, feeding, sealing, punching and discharging.
[][]Machine should be observed very carefully during blistering operation.
[][]Press the stop button in machine after completes the blister operation.
[][]Record the machine operation start time and end time & other parameters in the ‘Equipment Log Book’ .

Dismantling of Change Parts

[][]Change parts should be removed sequentially from the machine with the help of others.
[][]Feeding Tray should be removed by loosing screw nuts.
[][]Guide Rail should be removed by loosing nuts.
[][]Forming Set (Upper & Lower Plate) should be removed by loosing screw nuts.
[][]Cutter should be removed by loosing nuts.
[][]Sealing Upper Plate should be removed by loosing clamp lock.
[][]Sealing Lower Plate should be removed by loosing screw nuts.
[][]Cooling Plate should be removed by loosing screw nuts.
[][]Perforation/ Slitting should be removed by loosing screw nuts.
[][]Heating Plate (In-case of Alu-PVC) should be removed by loosing nuts.
[][]Embossing Plate should be removed by loosing screw nuts and clamp lock.
[][]Change parts should be kept on clean pallets with “TO BE CLEANED” label.

Machine Cleaning

[][]All documents, previous product container and any materials should be removed from the room.
[][]The dust should be cleaned around the machine with the help of vacuum cleaner.
[][]The surface of the machine should be cleaned with lint free cloths with Purified Water or defined cleaning solution starting from top to downwards sequentially at first ceiling, wall, machine and floor.
[][]Safety covers (Door) should be cleaned by the use of wetted smooth lint free cloth with purified water.
[][]Glass and plastic materials should be cleaned by lint free smooth cloth with purified water.
[][]The machine should be moped with a lint free cloth using purified water.
[][]Finally, the machine should be moped with dried lint free cloth.
[][]Record should be taken in equipment machine log book.
[][]Machine accessories should be transferred to the wash room.
[][]“CLEANED” label should be attached to the machine.
[][]Change parts should be dismantled and kept on a clean trolley or pallets with status label and kept the trolley on the washing room for the cleaning at the end of product run.
[][]After cleaning completion the change parts should be stored in tool store with “CLEANED” label.

Annexure:

Annexure I Equipment Use Log Book

Blister Packaging Machine Set Up, Operation & Cleaning Read More »

ROPP Cap Sealing Machine Set Up, Operation & Cleaning

ROPP Cap Sealing Machine, Purpose :

ROPP Cap Sealing Machine, The purpose of this SOP is to describe the Operation and cleaning procedure of ROPP Cap Sealing Machine (Model: PPM-35) in order to comply with cGMP standard.

ROPP Cap Sealing Machine, Scope :

The scope of the procedure is applicable to the ROPP Cap Sealing Machine (Model: PPM-35) at the Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Setting, operation and cleaning of the Cap Sealing Machine (Model: PPM-35)
[][]Maintaining Equipment Log Book.

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure:

Precaution:

[][]Ensure that area & equipment are clean and suitable to start the operation.
[][]Use protective suit, surgical gloves, head gear, cotton mask, and safety goggles during sealing operation.
[][]In case of emergency, press the emergency switch to stop the machine.

Machine Assembling

[][]Set the base of the machine by specific nut and attach the bottle adjuster.
[][]Set the sealing wheel according to the neck diameter of the bottle.
[][]Fix the bottle size by moving the base.

Machine Operation

[][]Load the bottle on the SS table.
[][]Fix the plastic stopper and aluminum cap on the empty bottle.
[][]Turn on the main switch of the machine.
[][]Take a bottle on the base.
[][]Seal it by the moving sealing wheel.
[][]Check the leakage by leak test apparatus.
[][]If sealing is accurate then another eight empty bottle have to seal.
[][]Take them again for leak test.
[][]Continue the sealing operation if sealing is accurate.
[][]Turn off the all switch gradually after complete the sealing operation.
[][]Record the machine start & end time and other parameters in the ‘Equipment Log Book’

Machine Dismantling

[][]Turn the main switch off.
[][]Dismantle the parts like moving sealing wheel, bottle adjuster unit and transfer them to the wash bay.

Machine cleaning

[][]Remove dusts from the machine with a vacuum cleaner. Collect dust from machine body.
[][]Clean all the machine parts with dry lint free cloth.
[][]Use potable water to clean the machine body and holding screw.
[][]Use hot water to clean all the product contact parts & finally rinse with purified water.
[][]Clean and swab all the parts with lint free cloth to remove water.
[][]After final cleaning affix the ‘CLEANED’ label.
[][]Record the cleaning parameters on the ‘Equipment Log Book’.

ROPP Cap Sealing Machine Set Up, Operation & Cleaning Read More »

Auger Filling Machine Set Up, Operation & Cleaning

Auger Filling Machine, Purpose :

Auger Filling Machine, The purpose of this SOP is to describe the setting, operation and cleaning procedure of Auger filling Machine (Model: GZF30B) in order to comply with cGMP standard.

Auger Filling Machine, Scope :

The scope of the procedure is applicable to the Auger filling machine (Model: GZF30B) at the Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]PLC = Programmable Logic Controller.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Setting, operation and cleaning of the Auger filling Machine (Model: GZF30B)
[][]Maintaining Equipment Log Book

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure:

Precaution:

[][]Ensure that area & equipment are clean and suitable to start the operation.
[][]Before entering the filling room use protective suit, surgical gloves, head gear, cotton mask, and safety goggles during filling operation.
[][]Do not insert hands inside the hopper during operation; keep the hopper closed after loading.
[][]Make sure that powder is not deposited in hopper, dosing unit and other parts of the machine that must be observed very carefully.
[][]In case of emergency, press the emergency switch to stop the machine.

Machine Assembling

[][]Set the dosing unit by specific nut and attach the supporting parts of dosing unit.
[][]Set the powder hopper with its supporting parts.
[][]Fix the size of the bottle on the machine.
[][]Set the parameters of the machine such as Set Quantity, Actual Quantity and Output on the PLC.

Machine Operation

[][]Load the bottle on the SS table.
[][]Load the powder in hopper and close the lid of hopper.
[][]Turn on the main switch of the machine.
[][]Turn on the vibrator switch.
[][]Mix the powder in the hopper by rotating stick.
[][]Set the filled weight on the PLC.
[][]Adjust the filled weight by pressing leg punch in the empty glass bottle.
[][]Check the fill weight of eight bottles after setting the volts in dose wheel.
[][]Continue the filling operation if fill weight is accurate.
[][]Turn off the all switch gradually after complete the filling operation.
[][]Record the machine start & end time and other parameters in the ‘Equipment Log Book’

Machine Dismantling

[][]Turn the main switch off.
[][]Collect the powder from the hopper and dosing unit by vacuum cleaner.
[][]Dismantle the parts like hopper, auger and dosing unit and transfer them to the wash bay.

Machine cleaning

[][]Remove dusts from the machine with a vacuum cleaner. Collect dust from the hopper, dosing unit, operation panel and machine body.
[][]Clean all the machine parts with dry lint free cloth.
[][]Use potable water to clean the machine body, all product contact parts and holding screw.
[][]Use hot water to clean all the product contact parts.
[][]Finally rinse the machine body, all product contact parts, holding screw and other parts with purified water.
[][]Clean and swab all the parts and the machine body with lint free cloth to remove water.
[][]After final cleaning affix the ‘CLEANED’ label.
[][]Record the cleaning parameters on the ‘Equipment Log Book.

Annexure:

Annexure I Equipment Use Log Book

Auger Filling Machine Set Up, Operation & Cleaning Read More »

Capsule Polishing Machine Set Up, Operation And Cleaning Procedure

Capsule Polishing Machine, Purpose :

Capsule Polishing Machine, The purpose of this SOP is to describe the setting, operation and cleaning procedure of the Capsule Polishing Machine (Model: SF-40N) in order to comply with cGMP standard.

Capsule Polishing Machine, Scope :

The scope of the procedure is applicable to the Capsule Polishing Machine (Model: SF-40N) at the Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Set up, operation and cleaning of the Polishing Machine (Model: SF-40N)
[][]Maintaining Equipment Log Book

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Annexure:

N/A.

Procedure

Precautions :

[][]Make sure that the main power switch is OFF position before and after operation.
[][]Ensure that area & equipment are clean and suitable to start the operation.
[][]Before entering the capsule polishing room use protective suit, surgical gloves, head gear, cotton mask, and safety goggles during polishing operation.
[][]Do not insert hands inside the hopper during operation.
[][]Make sure that capsule is not deposited in hopper and other parts of the machine that must be observed very carefully.
[][]In case of emergency, press the emergency switch of the main encapsulation machine to stop the machine.

Machine Assembling

[][]Set the capsule polishing brush by specific nut and attach the SS cover of the machine.
[][]Set the capsule hopper.
[][]Fixed the empty capsule shell feeder on the machine.
[][]Set the air pressure of the machine.

Machine Operation

[][]Turn ON the main switch of the machine. Then turn ON the switch of the capsule polishing machine.
[][]Turn on the air pressure valve and adjust the air pressure 0.15 to 0.2 bars.
[][]Load the capsule on the hopper.
[][]Check the capsule is polishing accurately.
[][]Continue the polishing operation if capsule polishing is accurate.
[][]Turn OFF all switch gradually after complete the polishing operation.
[][]Record the machine operation parameters in the ‘Equipment Log Book’

Machine Dismantling

[][]Turn the main switch OFF.
[][]Collect the dust from the hopper by vacuum cleaner.
[][]Dismantle the parts like hopper, machine cover, brush and empty shell feeder and transfer them to the wash bay.

Machine Cleaning

[][]Remove dusts from the machine with a vacuum cleaner. Collect dust from the hopper machine body.
[][]Clean all the machine parts with dry lint free cloth.
[][]Use potable water to clean the machine body, all product contact parts and holding screw.
[][]Use hot water to clean all the product contact parts like capsule polishing brush.
[][]Finally rinse the machine body, all product contact parts, holding screw and capsule polishing brush with purified water and dry the brush properly after cleaning.
[][]Clean and swab all the parts and the machine body with lint free cloth to remove water.
[][]After final cleaning affix the ‘CLEANED’  label.
[][]Record the cleaning parameters in the ‘Equipment Log Book.

Annexure:

Annexure I Equipment Use Log Book

Capsule Polishing Machine Set Up, Operation And Cleaning Procedure Read More »

Capsule Filling Machine Set Up, Operation and Cleaning

Capsule Filling Machine , Purpose :

Capsule Filling Machine , The purpose of this SOP is to describe the setting, operation and cleaning procedure of the Capsule Filling Machine (Model: SF-40N) in order to comply with cGMP standard.

Capsule Filling Machine , Scope :

The scope of the procedure is applicable to the Capsule Filling Machine (Model: SF-40N) at the Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Set up, operation and cleaning of the Capsule Filling Machine (Model: SF-40N)
[][]Maintaining Equipment Log Book

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Manager, Quality Assurance

[][]To approve the Document.

Procedure :

Precautions :

Safety

[][]Never run the machine with its door open.
[][]Use face mask, rubber gloves and protective clothing during handling of materials.
[][]Keep the switches “OFF” during break-time and at the end of the job.

Special Instruction

[][]Ensure the Capsule Filling machine is properly cleaned.
[][]Compressed air pressure should be set at 6 kg/cm².
[][]Filters on the dry vacuum must be cleaned regularly. Vacuum should be used for cleaning.
[][]Do not use water or a solvent to wash filters on the vacuum.
[][]Never wash filters with water.
[][]Lubricate all moving parts as per schedule.
[][]Use correct lubricants for all moving parts.
[][]Never repair, adjust, clean or lubricate any moving parts while the machine is in motion.

Machine Assembling

[][]Open the site glass of all sides
[][]Set the desired side pusher and tighten the set screws.
[][]Set the desired race way and tighten the set screws.
[][]Set the desired feeder and tighten the set screws.
[][]Set the block and tighten the set screws.
[][]Adjust the side pusher and down pusher.
[][]Press “up” button on the display and make powder hopper in maximum height.
[][]Install the desired dose filling plate.

Adjust the dosing device.

Align the stop plate with the tamping pin holes. Insert the tamping pins and pull the stop plate to lock around the neck of the pins. Tighten the four set screws.
For alignment of dosing disk with set plate-
Loosen the dosing disk set screws.
Insert six adjustment bars through the holes on the set plate.
Adjust the position of the dosing disk until all six adjustment bars fall freely into the disk holes
[][]Tighten set screws without moving the disk.
[][]Check the alignment with six adjusting bars to see if all bars fall freely without touching the disk hole wall.
[][]Turn the machine 2-3 revolutions by the hand wheel to see the adjustment bars fall freely at all six points.
[][]Adjust the tamping pins into the set plate holes and adjust set screws.
[][]Adjust the closing pin holder and joint plate depending on the capsules size.
[][]Adjust height of dosing disk (0.5mm).
[][]Check the correct setting of change parts listed below
Upper capsule segment
Lower capsule segment
Capsule feeder
Race way
Side pusher
Capsule stopper plate
Size ring
Dose filling plate (for pellet)
Tamping pins (for powder)
Dosing disk (for powder).

Machine Operation

[][]Check the cleanliness of the filling machine. Give clearance to run the machine.
[][]Switch ON the main power switch.
[][]Open compressed air supply valve.
[][]On the control power of automatic data controller.
[][]Race machine through a few steps via the hand wheel of the main drive.
[][]Charge capsule hopper with empty capsule shell.
[][]Clear capsule locking at capsule magazine.
[][]Turn key switch MANUAL MODE to INCHING.
[][]Switch on vacuum Press the illuminated pushbutton VACUUM

Powder Station

[][]Charge powder container with powder
[][]Adjust powder height mechanical tamping pin adjustment
[][]Adjust powder filling level height on dosing disk
[][]Run machine in inch mode for 6-7 turnings until all segments are filled with capsules Press the pushbutton START Subsequent check capsule weight.
[][]If necessary, adjust the capsule weight by adjusting the tamping pin and the powder height.

Pellet Filling Station

[][]Charge pellet hopper with pellet.
[][]Open the shutter > moving it upwards
[][]Start operation of the pellet station.
[][]Run machine through several cycles in inch mode >press the pushbutton START and then check capsule weight with pellets.
[][]Let the machine running >Press the pushbutton START
[][]Check again capsule weight and correct if necessary.
[][]Start machine in automatic mode.

Control machine running

[][]Stop automatic mode > Press key STOP.
[][]Shut Off compressed air supply.
[][]Clean the machine as per current version of SOP.

Machine Cleaning

[][]Take the main switch to OFF position.
[][]Remove the pellet hopper by removing four screws.
[][]Remove pellet doser by removing four nuts.
[][]Remove the discharge chute by removing two nuts.
[][]Rotate the hand wheel, situated at the lower portion of right side of the machine, to bring capsule segment no. 1 to backside of the machine.
[][]Remove the upper capsule segment one by one by removing two nuts using allen key. Clean them with dry cloth, then tape water & finally rinse with purified water and keep them in their respective box.
[][]Remove the lower capsule segment one by one by removing two nuts using allen key from the two centering pins. Clean them with dry cloth, then tape water & finally rinse with purified water and keep them in their respective box.
[][]Loosen two set screws and remove the block of shell doser.
[][]Loosen two set screws and remove the feeder. Clean using compressed air.
[][]Loosen two set screws and remove the race way. Clean using compressed air.
[][]Loosen two set screws and remove the side pusher. Clean using compressed air.
[][]Keep the shell feeder, race way and side pusher in their respective box.
[][]Remove the capsule stopper plate by removing two nuts.
[][]Remove size ring, clean and set the desired size ring.
[][]Remove any loose powder inside the cleaning segment holes by blowing compressed air and by applying vacuum.
[][]Disassemble the upper part of the granules doser, dose controller and dose filling plate. Clean them with organic solvent like isopropyl alcohol. (For pellets).
[][]Loosen the coupling for the agitator screw and driving shaft. (For powder)
[][]Remove dust from the agitator screw, driving shaft and powder tank with clean cloth. Wash them 2-3 times with potable water then rinse with purified water. Wipe them with dry clean cloth. Allow drying in air conditioned room.
[][]Loosen the set screws and remove the fastening plate by lifting and tilting. Clean the fastening plate with cloth, then tape water & finally rinse with purified water and keep them in their respective box
[][]Loosen the set screws and remove the dosing disk and chamber. Clean the dosing disk and chamber with cloth, then tape water & finally rinse with purified water and keep them in their respective box
[][]Loosen the lock screws, turn the adjusting screws all the way up and lift the pin holder to remove thirty pins with the holder.
[][]To remove pins from the holder, loosen the set screws, pull the stop plate forward, and remove pins. Clean them with tape water & finally rinse with purified water and keep them in their respective box
[][]After final cleaning affix the ‘CLEANED’  label.
[][]Record the cleaning parameters in the ‘Equipment Log Book’

Annexure:

Annexure I Equipment Use Log Book

Capsule Filling Machine Set Up, Operation and Cleaning Read More »

Tablet Coating Machine Set Up, Operation & Cleaning

Tablet Coating Machine, Purpose:

Tablet Coating Machine, The purpose of this SOP is to describe the setting, operation and cleaning procedure of Tablet Coating Machine (Model: FC-39) in order to comply with cGMP standard.

Tablet Coating Machine, Scope:

The scope of the procedure is applicable to the Tablet Coating Machine (Model: FC-39) at the Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]PLC : Programmable Logic Controller.
[][]CIP : Clean In Place.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Setting, operation and cleaning of the Tablet Coating Machine (Model: FC-39)
[][]Maintaining Equipment Log Book

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure: Tablet Coating Machine

Precaution:

[][]Ensure the outlet duct is open.
[][]Ensure the inlet duct is open.
[][]Keep the doors closed during operation and after completion of job.
[][]Check air pressure.
[][]Use face mask, rubber gloves and protective clothing during handling of materials.

Machine Assembling

[][]Before operation assemble the machine accessories that are necessary for operation.
[][]Place the spray gun at the holding arm. Then, enter the spray gun holding arm into the coating pan.
[][]Connect the peristaltic pump with the spray gun.
[][]Test whether coating pan rotates smoothly without any abnormal noise after activation. Check that rotation direction is correct.

Machine Operation.

[][]Switch on the Machine.
[][]Unlock and open the inlet port cover of the machine.
[][]Load tablets into the coating pan. Total tablet load should not exceed the maximum working load and should not be less than the minimum working load.
[][]Securely close the coating pan chamber cover and clamp.
[][]Pan motor ‘‘ON/OFF’ from the PLC.
[][]Warm up the tablets without spraying on the tablet bed.
[][]Start spraying phase by pressing the pump start button in manual mode or Spray key in Auto mode. Adjust dosing volume by changing the rpm of the peristaltic pump.
[][]After spraying, stop the Spray by pressing Pump ON/OFF button. Dry the tablets until required.
[][]Unload the tablets from the coating pan when desired tablet temperature is attained.
[][]Record the machine operation start time & end time and other parameters on the ‘Equipment Log Book’

Machine Dismantling

[][]Remove the spray system and dismantle.
[][]Remove the pan outlet dumber.

Machine Cleaning: Tablet Coating Machine

[][]Switch off outlet damper, outlet blower, pan motor.
[][]Open all safety doors.
[][]Switch on the peristaltic pump by pressing “Switch on button”.
[][]Wash the inside of tube by spraying with hot water.
[][]Then wash the tube with purified water.
[][]Pass compressed air through tube to dry inside of tube.
[][]Clean the Spray gun nozzle with hot water and soft brush.
[][]Now discharge the water with dissolved materials.
[][]Now hot water is applied inside the chamber through CIP system to remove materials fixed hardly on the chamber surface.
[][]Re-wash the machine with purified water as required through CIP system.
[][]Wash the machine with lint free cloth.
[][]Clean inlet ports, discharge port, mixing chamber and external surface with potable water, hot water & purified water.
[][]Wipe the water droplets with lint free cloth, and dry the machine with compressed air.
[][]After final cleaning affix the ‘CLEANED’ label.
[][]Record the cleaning parameters on the ‘Equipment Log Book’

Annexure:

Annexure I Equipment Use Log Book

Tablet Coating Machine Set Up, Operation & Cleaning Read More »

Tablet Metal Detector Set Up, Operation And Cleaning

Tablet Metal Detector ,Purpose:

Tablet Metal Detector , The purpose of this SOP is to describe the setting, operation and cleaning procedure of MET 30+ Pharmaceutical Metal Detector Machine in order to comply with cGMP standard.

Tablet Metal Detector , Scope:

The scope of the procedure is applicable to the MET 30+ Pharmaceutical Metal Detector Machine at the Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Operation and cleaning of the MET 30+ Pharmaceutical Metal Detector
[][]Maintaining Equipment Log Book

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the document

Procedure:

Precaution :

[][]Use face mask, rubber gloves and protective clothing during handling of materials.
[][]Ensure Electric line is properly connected.

Machine Assembling

[][]Set the discharge chute into the main body of the machine.
[][]Set the rejected tablet containing bucket in the lower part of the machine.
[][]Adjust the alignment of the machine with respect to main machine.
[][]Ensure all the settings are properly done.

Machine Operation

[][]Connect electrical cable to the machine.
[][]Switch ON the main power of the machine.
[][]Set the programs from the control panel of the machine.
[][]Pass the tablet through the discharge chute and reject the tablet having metallic content.
[][]Record the machine start & end time and other parameters in the ‘Equipment Log Book’

Machine Dismantling

[][]Switch OFF the main power of the machine.
[][]Remove the discharge chute.
[][]Remove the bucket from the lower part of the machine.

Machine Cleaning

[][]Remove dusts from the machine with a vacuum cleaner.
[][]Clean all the machine parts with dry lint free cloth.
[][]Use potable water to clean the machine body.
[][]Use hot water to clean all the product contact parts.
[][]Finally rinse the machine body, all product contact parts.
[][]Clean and swab all the parts and the machine body with lint free cloth to remove water.
[][]After final cleaning affix the ‘CLEANED’ label.
[][]Record the cleaning parameters on the ‘Equipment Log Book’

Annexure:

Annexure I Equipment Use Log Book

Tablet Metal Detector Set Up, Operation And Cleaning Read More »

Spare Parts Cleaning, Labeling And Storage

Spare Parts , Purpose:

Spare Parts , To lay down the procedure for Cleaning, Labeling & Storage of spares in spare parts room at the Production Area.

Spare Parts , Scope:

This SOP is applicable for the Production Area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows :

Operator

[][]To follow the laid down procedure

Executive, Production

[][]To monitor and check the procedure is followed

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure :

General Instructions

[][]Store all the clean and dry spare parts in the lockers or on the racks in separate polythene bags. Never keep any parts in the spare parts room without covering them.
[][]All the equipment parts stored in the spare parts room must be affixed with properly filled status label to identify the parts and its cleaning status.
[][]Production supervisor must regularly check the status label to avoid any error in the labeling.

Storing of utensils and accessories

[][]Store all the clean utensils and accessories in the lockers or in the racks in the separate polythene bags. Never keep any parts in the spare parts room without covering them.
[][]All the equipment parts stored in the spare parts room must be affixed with properly filled status label to identify the parts and its cleaning status.
[][]Record the use of utensils and accessories in the ‘Spares Use Register Book’ (Annexure I).
[][]Production supervisor must regularly check the status label to avoid any error in the labeling.

Storing of Dies and punch boxes

[][]Wipe the outside of the boxes with clean duster, then with 70% IPA solution (if necessary). Clean the dies and punches according to the Tablet Compression Machine SOP.
[][]Record the use of dies and punches in the ‘Spares Use Register Book’ for using dies and punches. Check the condition of punches before issuing and receiving.
[][]Storing of different size change parts of capsule filling machine
[][]Keep the clean and dry machine parts in the spare parts room in separate polybag and affix with properly filled status label.
[][]Record the use of Capsule Filling Machine change parts (e.g. Cutter, forming channel etc.) in the ‘Spares Use Register Book’.

Storing of blister change parts

[][]Wipe the outside of the boxes with clean cloth, then with 70% IPA solution (if necessary).
[][]Keep the clean and dry blister change parts in the locker dedicated for blister change parts.
[][]If there is no spare space in the locker keep the change parts in a polybag with proper status label and then place in clean pallet.
[][]Record the use of Blister parts (e.g. Cutter, forming channel etc.) in the ‘Spares Use Register Book’. Check the condition of blister parts before issuing and receiving.

Annexure:

Annexure I Spare Parts Usage Log Register

Spare Parts Cleaning, Labeling And Storage Read More »

Tablet Dedusting Machine Set Up, Operation & Cleaning

Tablet Dedusting Machine, Purpose:

Tablet Dedusting Machine, The purpose of this SOP is to describe the setting, operation and cleaning procedure of SEJONG Tablet Dedusting Machine in order to comply with cGMP standard.

Tablet Dedusting Machine, Scope:

The scope of the procedure is applicable to the SEJONG Tablet Dedusting Machine at the Production area  of XX  Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Setting, operation and cleaning of the Machine
[][]Maintaining Equipment Log Book

Executive, Production

[][]To monitor and check the laid down procedure

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Annexure:

N/A

Procedure:

Precaution :

[][]Use face mask, rubber gloves and protective clothing during handling of materials.
[][]Ensure electric and air line are properly connected.
[][]Machine Assembling
[][]Set the perforated plate in machine.
[][]Fixed the upper lid properly by holding screw.
[][]Ensure all the screws are connected properly.

Machine Operation

[][]Connect electrical cable of Dedusting Machine to the main compression machine.
[][]Connect compressed air line to Dedusting Machine.
[][]Switch ON the main power of Dedusting Machine.
[][]Adjust the vibration level by tuning volume.
[][]During tablet compression tablet passes through the discharge chute of compression machine to the Dedusting machine.
[][]Record the machine start & end time and other parameters in the ‘Equipment Log Book’

Machine Dismantling

[][]Switch OFF the main power of the Dedusting Machine.
[][]Remove the compressed air line from the Dedusting Machine.
[][]Open the upper lid of the machine.
[][]Remove the perforated plate of the machine.

Machine Cleaning

[][]Remove dusts from the machine with a vacuum cleaner.
[][]Clean all the machine parts with dry lint free cloth.
[][]Use potable water to clean the machine body, all product contact parts and holding screw.
[][]Use hot water to clean all the product contact parts.
[][]Finally rinse the machine body, all product contact parts, holding screw and other parts with purified water.
[][]Clean and swab all the parts and the machine body with lint free cloth to remove water.
[][]After final cleaning affix the ‘CLEANED’ label.
[][]Record the cleaning parameters on the ‘Equipment Log Book’

Tablet Dedusting Machine Set Up, Operation & Cleaning Read More »

Tablet Compression Machine Set Up, Operation & Cleaning

Tablet Compression Machine, Purpose :

Tablet Compression Machine, The purpose of this SOP is to describe the setting, operation and cleaning procedure of SEJONG Tablet Compression Machine (Model: MRC-30N) in order to comply with cGMP standard.

Tablet Compression Machine, Scope :

The scope of the procedure is applicable to the SEJONG Tablet Compression Machine (Model: MRC-30N) at the Production area of of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]PLC : Programmable Logic Controller.
[][]RPM : Rotation Per Minute.

Responsibilities:

[][]The roles and responsibilities are as follows:

Operator

[][]Setting, operation and cleaning of the SEJONG Tablet Compression Machine (Model: MRC-30N).
[][]Maintaining Equipment Log Book.

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Manager, Quality Assurance

[][]To approve the Document.

Annexure:

N/A.

Procedure:

Precaution:

[][]Check for leakage of oil & the connection state.
[][]Check for proper locking of the dies with die setting pin.
[][]Check the assembling of die & punch set.
[][]The cover doors must be kept in close position during operation.
[][]Check the setting components like thickness, weight, hardness & other parameters.
[][]Use face mask, rubber gloves and protective clothing during handling of materials.

Machine Assembling

[][]Open the site doors of all side.
[][]Keep available all the dies, punches & other necessary parts near the machine.

Setting of Die

[][]Ensure that the die pockets are cleaned.
[][]Smear the die with food grade oil and place in the die pocket.
[][]Press the die down with finger to locate accurately in the die pocket.
[][]Once the die is located, enter the die insert bar through the upper punch guide hole and allow dropping.
[][]The die will enter in the pocket; apply additional force through die insert bar until the die is fully down on the die pocket.
[][]In order to set the shaped die enter the upper punch first and align the die bore with the upper punch tip and gently push the die with the punch to enter in the die pocket, then apply additional force through die insert bar to fully down the die in the die pocket.
[][]Ensure that the top face of the die is perfectly flash with the die table.
[][]Tighten the die setting pin with the torque after greasing the tip of die setting pin. Ensure that the die is flash with the die table after tightening. Do not run the machine if die setting pin is not properly tightened.
[][]Set all blank dies (D tooling) in respective die pocket in the same procedure by rotating the turret manually with the help of hand wheel.

Setting of lower punch

[][]Take out the change rail and put the lower punch through the lower space of the change rail. At this time grease thinly on the head of punch.
[][]Move the disk (turret) to the next station through rotating with hand wheel. Make the punch movement smoothly not to be stuck in the down rail.
[][]Assemble every punch with same method.
[][]Assemble the change rail.

Setting of upper punch

[][]Ensure that the punch guide holes and punches are clean.
[][]Take out the change rail and put the upper punch through the upper space of the change rail.
[][]Place all the punches in the punch holes by rotating the disk (turret) with the hand wheel and check that each punch is free to move in its guide and capable of dropping in to the cam track by its own weight.
[][]Rotate the turret at least one full turn by hand wheel to recheck to ensure that the upper punches enter the die bores without any friction and they run freely throughout the cam system.
[][]Install the mechanical force feeder, scrapers & other parts of the machine. Ensure that no part is in touch with the main disk (turret). Tighten the bolts of mechanical force feeder. Rotate the machine manually through hand wheel to ensure machine rotates without hindrance.
[][]Install the tablet ejection chute of the machine. Ensure that no part of the machine is in contact with the turret. Tighten the screw of the ejections chute.
[][]Install the side covers.
[][]Install the hopper above the mechanical force feeder.
[][]Connect the coupling with the feeder drive, shaft. Lock the coupling.
[][]Connect the powder sensor with the hopper.
[][]Check that all nut bolts are tightened correctly.
[][]Close all side doors. The machine is ready to use.

Machine Operation

[][]Rotate the machine through hand wheel and check that there is no abnormal sound in the machine.
[][]Ensure the connection of air supplying line.
[][]Switch on the main power on the back of machine.
[][]Again switch on the key of the operation box bottom part by turning the key clockwise.
[][]Login the password.
[][]If the screen is touched and there is no alarm in the machine the screen will be conversed into OPERATION PANEL mode. When the alarm is working, the screen will show SAFETY MESSAGE mode.
[][]Rotate the machine through hand wheel and check that there is no abnormal sound in the machine.
[][]Ensure the connection of air supplying line.
[][]Switch on the main power on the back of machine.
[][]Again switch on the key of the operation box bottom part by turning the key clockwise.
[][]Login the password.
[][]If the screen is touched and there is no alarm in the machine the screen will be conversed into OPERATION PANEL mode. When the alarm is working, the screen will show SAFETY MESSAGE mode.

Operation Panel Setting

Operation condition

[][]FEEDER CONTROL (select AUTO/HAND/INCH mode)
[][]FEEDER CONTROL (RPM control for HAND mode)
[][]DUST COLLECTOR (ON/OFF switch)
[][]TARGET QUANTITY (ON/OFF switch)
[][]POWDER ALARM (powder sensor ON/OFF switch)
[][]BUZZER (ON/OFF switch)
[][]MAIN MOTOR CONTROL (disk RPM control)

Set Panel Setting

[][]In order to set the product condition converse into SET PANEL mode through touching SET PANEL button in bottom of the screen.

Product condition

[][]PRETHICKNESS (Thickness setting in the pre-pressure station)
[][]FILLING DEPTH (Tablet weight setting)
[][]MAIN THICKNESS (Tablet thickness setting)
[][]SELECT CAM (Cam selection)
[][]FEEDER RPM % (In AUTO mode, RPM setting)
[][]POWDER SUPPLY TIME (Time setting from powder shortage alarm to machine stop)
[][]TARGET QUANTITY (Target quantity setting)
[][]OIL LUBRICATION SETTING (Punch lubrication setting)
[][]HELP MODE (Description of touch screen function)

Tablet weight control

[][]In case that the weight is not accurate, generally the weight is adjusted through the touch screen. But, besides of that the small amount of powder filling can be adjusted with the speed of mechanical feeder agitator, also Tablet thickness control
[][]Tablet thickness is adjusted by lower roll’s height and it is operated through touch screen.

Hardness control

[][]Hardness is adjusted by following methods-
[][]Control compressing force in pre & main pressure section

Inch operation

[][]Before starting the production, INCH operation is recommended though the operation box.
[][]Control pre & main thickness with the maximum value.
[][]Set pre & main thickness according to the production data.
[][]If every configuration is ready, check SAFETY MESSAGE screen.
[][]If there is any problem in the machine, solve the problem with proper method.
[][]After setting variables like filling cam selection, pressure, filling depth, penetration depth, tablet thickness and etc run the machine. Especially, for the safety, before starting the product, inching operation should be done.
[][]Inch the mechanical feeder for a few seconds to distribute the granules uniformly within the die bore.
[][]Off the manual mode.
[][]On the auto mode.

[][]Inch the machine one revolution & check the weight.
[][]Adjust the filling depth to get the required weight. (If necessary).
[][]Adjust the thickness controller to get the required hardness and thickness.
[][]Record the machine start & end time and other parameters in the ‘Equipment Log Book’

Machine Dismantling

[][]Open the site doors of the machine.
[][]Place a poly bag on powder outlet; remove the material lock from the mechanical force feeder, and on the mechanical force feeder, excess materials will be flown in to the poly bag.
Switch off the machine.
[][]Adjust the filling depth wheel and thickness adjustment wheel at the lowermost position.
[][]Loosen the ejection chute holding screw and remove the ejection chute.
[][]Remove the hoper and powder sensor carefully.
[][]Unlock the feeder drive shaft from the coupling and keep aside. Loosen the mechanical force feeder holding screw then remove the mechanical force feeder.
[][]Remove the upper punch change rail.
[][]Remove the upper punches.
[][]Remove the lower punch change rail.
[][]Punch will automatically come out of the cavity, if required press gently downward and collect the punch.
[][]Remove all the lower punch in the same manner.
[][]Loosen all the die setting pins up to maximum limit.
[][]Enter the die insert bar through the lower punch loading cavity. Then gently apply pressure upward to remove the die. Die will come out of the die pocket. Remove all the dies in the same manner.

Machine Cleaning

[][]Remove dusts from the machine with a vacuum cleaner. Collect dust from the turret, punch holding cam, operation panel and machine body.
[][]Clean all the machine parts with dry lint free cloth. Clean the die bore, die pocket & die table with a flush brush. Use brush to clean any material sticking in the machine parts, pin and knobs.
[][]Use potable water to clean the turret, machine body, cam, punch holding cavity, die, die setting pin and other parts.
[][]Use hot water to clean all the above mentioned body parts & finally rinse with purified water.
[][]Clean and swab all the parts with lint free cloth to remove water.
[][]Close site doors and affix a ‘CLEANED’ label in the machine.

Cleaning of die and punches

[][]Clean the die and punch with lint free cloth to remove any particle in the die and punch.
[][]Flash the die bore with flash brush and use brush to clean any particle sticking with the die and punch.
[][]Clean the die and punch with potable water, use brush if necessary.
[][]Clean the die and punch with hot water and finally rinse with purified water.
[][]Remove any water present in the die and punch with lint free cloth.
[][]Smear the die and punches with food grade oil and store in the die punch cabinet.

Cleaning of mechanical force feeder

[][]Remove the screws of mechanical force feeder and open the cover of feeder housing
[][]Remove the paddle and paddle key from the machine and collect dust particle from the feeder housing with vacuum cleaner.
[][]Clean all the parts with lint free cloth.
[][]Clean all the parts with potable water, use Teflon brush if necessary
[][]Clean all machine parts with hot water and then rinse with purified water.
[][]Remove any water from the parts with lint free cloth.
[][]Assemble the paddle and cover in the feeder housing and take in a poly bag. Attach a ‘CLEANED’ label in the bag and store in the machine parts cabinet

Cleaning of hopper and ejection chute

[][]Clean all the powder with lint free cloth
[][]Use potable water to clean the hopper and the ejection chute, use Teflon brush where necessary.
[][]Clean the mentioned parts with hot water and then rinse with purified water.
[][]Clean and remove out any water remaining in the machine parts with lint free cloth.
[][]Wrap the change parts with poly bag, attach ‘CLEANED’ label in the poly bag and store in the machine parts cabinet.
[][]Record the cleaning parameters on the ‘Equipment Log Book’

Tablet Compression Machine Set Up, Operation & Cleaning Read More »

Cone Blender Set up, Operation & Cleaning

Cone Blender, Purpose:

Cone Blender, The purpose of this SOP is to describe the setting, operation and cleaning procedure of Cone Blender Machine (Model: DB-150) in order to comply with cGMP standard.

Cone Blender, Scope:

The scope of the procedure is applicable to the Cone Blender Machine (Model: DB-150) at the Production area of General block of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Operation and cleaning of the Cone Blender Machine (Model: DB-150)
[][]Maintaining Equipment Log Book

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Annexure:

N/A.

Procedure:

Precaution:

[][]The cone is in lock position.
[][]Keep the hydraulic trolley near to the machine.
[][]Keep the doors of lower chamber closed during operation and after completion of job.
[][]Use face mask, rubber gloves and protective clothing during handling of materials.

Machine Assembling

[][]Lock the double cone.
[][]Change the sieve of dry granulator as specified in Batch Manufacturing Record (BMR).
[][]Open the lid of double cone.
[][]Move the dry granulator to the open end of the double cone.
[][]Ensure the proper adjustment of dry granulator and double cone.
[][]Lift the product container with hydraulic trolley to adjust with the container holder.
[][]Lock the product container with the container holder.
[][]Lift the product container to the granulator head.
[][]Move the product bowl and granulator out to the normal position.
[][]Close double cone cover lid.

[][]Unlock double cone and rotate it.

Machine Operation

[][]Set the parameters such as time & rotation per minute.
[][]Start granulator and transfer the product by passing through the granulator with desired sieve to double cone.
[][]After completion of milling close the lid
[][]Unlock double cone and rotate it.
[][]When the Process stops, the double cone will incline because of product. User have to press “JOG” button to swing or arrange double cone to straight in lock position and then lock it.
[][]Open guard bar and remove lower cone by trolley then move product out.
[][]Record the machine operation start time & end time and other parameters on the ‘Equipment Log Book

Machine Dismantling

[][]Remove lower cone from the machine.
[][]Remove the dry granulator.

Machine Cleaning

[][]Remove dusts from the machine with a vacuum cleaner. Collect dust from the product cone, dry granulator and operation panel and machine body.
[][]Clean all the machine parts with dry lint free cloth.
[][]Use potable water to clean the machine body, all product contact parts and holding screw.
[][]Use hot water to clean all the product contact parts.
[][]Finally rinse the machine body, all product contact parts, holding screw and other parts with purified water
[][]Clean and swab with lint free cloth all the parts and the machine body to dry any water.
[][]After final cleaning affix the ‘CLEANED’ label.
[][]Record the cleaning parameters on the ‘Equipment Log Book’

Cone Blender Set up, Operation & Cleaning Read More »

Filter Bag Washing & Storage System

Filter Bag, Purpose :

Filter Bag, The purpose of this SOP is to describe the washing and storage procedure of Filter Bag in order to comply with cGMP standard.

Filter Bag, Scope :

The scope of the procedure is applicable to the Filter Bag at the Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Washing & Storage of Filter Bag.

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Manager, Quality Assurance

[][]To approve the Document.

Annexure:

[][]N/A.

Procedure

Filter Bag Washing

[][]First wash with potable water.
[][]Clean the filter bag by rubbing.
[][]Soak the filter bag in hot water.
[][]Add 1 % sodium lauryl sulfate (in case of sticky material) with potable water and then soak the filter bag for 30 minutes.
[][]Then wash the filter bag by rubbing with potable water.
[][]Finally wash with purified water.
[][]Hang the filter bag and then allow to dry in wash bay.

Filter Bag Storage

[][]After drying take the filter bag in a cleaned poly bag.
[][]Store the filter bag in HDPE drum.
[][]Place the drum in FBD store room.
[][]Then affix the ‘CLEANED’ label on the drum.

Filter Bag Washing & Storage System Read More »

Rapid Mixer Granulator Set Up, Operation & Cleaning

Purpose :

The purpose of this SOP is to describe the setting, operation and cleaning procedure of Rapid Mixer Granulator Machine (Model: M-150) in order to comply with cGMP standard.

Scope :

The scope of the procedure is applicable to the Rapid Mixer Granulator Machine (Model: M-150) at the Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

PLC : Programmable Logic Controller
CIP : Clean In Place

Responsibilities:

The roles and responsibilities are as follows:

Operator

Operation and cleaning of the Rapid Mixer Granulator Machine (Model: M-150).
Maintaining Equipment Log Book.

Executive, Production

To monitor and check the laid down procedure.

Manager, Production

To implement this correctly.

Manager, Quality Assurance

To approve the Document.

Rapid Mixer Granulator Set Up, Operation & Cleaning Read More »

Vibratory Sifter Set Up, Operation and Cleaning

Vibratory Sifter, Purpose :

Vibratory Sifter, The purpose of this SOP is to describe the setting, operation and cleaning procedure of Vibratory Sifter Machine (Model: BT-800-3S) in order to comply with cGMP standard.

Vibratory Sifter, Scope :

The scope of the procedure is applicable to the Vibratory Sifter Machine (Model: BT-800-3S) at the Production area of General block of Labaid Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A.

Responsibilities:

The Roles and Responsibilities are as follows:

Operator

Operation and cleaning of the Vibratory Sifter Machine (Model: BT-800-3S)
Maintaining Equipment Log Book

Executive, Production

To monitor and check the laid down procedure.

Manager, Production

To implement this correctly

Manager, Quality Assurance

To approve the Document

Procedure

Precautions :

[][]Make sure that the power cable is separated from the socket before and after operation.
[][]The sifter covers and lid are in lock position during operation.
[][]Use face mask, rubber gloves and protective clothing during handling of materials.
[][]Check the cleanliness of sifter, sieves and gasket before assembling of machine.
[][]Check the sieve for its integrity before and after completion of operation.

Machine Assembling

[][]Keep the necessary change parts near the sifter machine before assembling.
[][]Assemble the sifter by putting cover with discharge opening on top of body of sifter.
[][]Then set the clamp to tighten the cover.
[][]Then place required sieve.
[][]On the top of first cover set the second cover with discharge opening.
[][]Set the clamp to tighten the second cover.
[][]Place the required sieve.
[][]Set the third cover with discharge opening.
[][]Set the clamp.
[][]Set the lid cover of sifter.
[][]Set the clamp.

Machine Operation

[][]Connect the power cable to the socket for power supply.
[][]Switch on the machine by pressing green button on the lower part of the machine.
[][]Input the material through the lid opening.
[][]Sieve the material and collect sieved material through the cover discharge opening.
[][]After operation switch off the sifter machine by pressing red button on the lower part of machine.
[][]Record the machine operation parameters in the ‘Equipment Log Book’

Machine Dismantling

[][]Remove the clamp of lid cover.
[][]Remove the lid cover.
[][]Remove the clamp of third cover.
[][]Remove the third cover.
[][]Remove the clamp of second cover.
[][]Remove the second cover.
[][]Remove the sieve.
[][]Remove the clamp of first cover.
[][]Remove the cover.
[][]Remove the sieve.

Machine Cleaning

[][]Remove dusts from the machine body and other necessary parts with a vacuum cleaner.
[][]Clean all the machine parts with dry lint free cloth.
[][]Use potable water to clean the machine body, product contact parts, clamps and other machine parts.
[][]Use hot water to clean all the product contact parts.
[][]Finally rinse the machine body, product contact parts, clamps and other machine parts with purified water.
[][]Remove the water with lint free cloth.
[][]After final cleaning affix the ‘CLEANED’ label.
[][]Record the cleaning parameters in the ‘Equipment Log Book’

Vibratory Sifter Set Up, Operation and Cleaning Read More »

Dispensing Booth Operation and Cleaning

Dispensing Booth, Purpose :

Dispensing Booth, The purpose of this SOP is to describe the operation and cleaning procedure of Dispensing Booth (Model: Standard) in order to comply with cGMP standard.

Dispensing Booth, Scope :

The scope of the procedure is applicable to the Dispensing Booth (Model: Standard) at the Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Operation and cleaning of the Dispensing Booth (Model: Standard)
[][]Maintaining Equipment Log Book

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Annexure:

[][]N/A.

Procedure

Precautions:

[][]The working person must follow safety procedures of works.
[][]For any trouble, disturbance switch OFF the Dispensing Booth.

Machine Operation

[][]Check the machine first physically.
[][]Check electric connection and mechanical set up.
[][]Machine switch on.
[][]Light on and blower on.
[][]Open the door.
[][]After completion desired work clean the Laminar Unit properly.
[][]Close the door and switch off main switch.
[][]Switch ON Dispensing Booth.
[][]Switch ON Light.
[][]Switch ON the Laminar Air Flow.
[][]Increase or decrease air flow by pressing up/down button.
[][]Warm up the Dispensing Booth for 30 minutes before starting dispensing.
[][]Record the machine operation start time & end time and other parameters on the ‘Equipment Log Book’

Machine Cleaning

[][]Remove dusts from the dispensing booth with a vacuum cleaner and then clean with lint free cloth.
[][]Use wet cloth to clean the booth.
[][]Wipe the water with lint free cloth.
[][]After final cleaning affix the ‘CLEANED’ label.
[][]Record the cleaning parameters in the ‘Equipment Log Book’

Dispensing Booth Operation and Cleaning Read More »

Dust Collector Set Up, Operation & Cleaning

Dust Collector , Purpose:

Dust Collector , The purpose of this SOP is to describe the setting, operation and cleaning procedure of Dust Collector in order to comply with cGMP standard.

Dust Collector , Scope:

The scope of the procedure is applicable to the Dust Collector at the Production area of of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]N/A

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Setting, operation and cleaning of the it
[][]Maintaining Equipment Log Book

Executive, Production

[][]To monitor and check the laid down procedure

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure:

[][]Machine Assembling
[][]Open dust collectors lid.
[][]Set the filter bag inside the Machine.
[][]Set the upper lid cover of the Machine.
[][]Connect the dust collecting hose pipe.

Machine Operation

[][]Connect electrical cable of it.
[][]Connect ithose pipe with Tablet Compression Machine.
[][]Switch ON the main power of it from the PLC of the compression machine.
[][]Record the operation start time & end time and other parameters on the ‘Equipment Log Book’

Machine Dismantling

[][]Switch OFF the compression Machine.
[][]Remove electrical connection.
[][]Remove dust collecting hose pipe from compression Machine.
[][]Remove the upper lid of the it.
[][]Remove the filter bag.

Machine Cleaning :

[][]Remove dusts from the machine with a duster.
[][]Use potable water to clean the machine body and filter bag.
[][]Finally clean with purified water.
[][]Clean and swab with lint free cloth all the parts and the machine body to dry any water.
[][]After final cleaning affix the ‘CLEANED’ label.
[][]Record the cleaning parameters on the ‘Equipment Log Book’

Annexure:

Annexure I Equipment Use Log Book

Dust Collector Set Up, Operation & Cleaning Read More »

Water Handling System at the Production Premises

Water Handling System, Purpose:

Water Handling System, To lay down the procedure of Water handling system at the Production premises.

Water Handling System, Scope:

This SOP is applicable for the Production Area of XX Pharmaceuticals Limited.

Definition / Abbreviation:

[][]N/A

Responsibilities:

[][]The Roles and Responsibilities are as follows :

Operator

[][]To follow the laid down procedure.

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Head of Quality Assurance

[][]To approve the Document.

Annexure:

[][]N/A

Procedure:

Precaution :

[][]During collection of hot water, wear heat resistance gloves.
[][]Before collection check all the point of connection & ensure that no one is open.
[][]Keep all inlet and outlet of circulating loop / storage tank and open ends of S.S. pipelines closed at the day end of work
[][]Always keep the water off-take valves closed at every use point after use.
[][]At the end of the day, ensure that no flexible hose pipe remains attached with the use point.
[][]Potable water should not be use in manufacturing process.

Types :

[][]Three types of water used in Manufacturing area.
Potable Water
Hot Water
Purified Water
Potable Water
[][]Connect pipe with the potable water system.
[][]Check availability of potable water in the line.
[][]Collect potable water from potable water mark water line.
[][]Use Pharma grade container to collect potable water for cleaning purpose.
[][]Transfer potable water to the respective production area by using SS trolley.
[][]After completion of work hang the pipe on the hanger.
[][]Keep both ends close with Alu foil after drain out of remaining water from pipe at the end of the day work.

Hot Water

[][]Connect pipe with the hot water system.
[][]Check availability of hot water in the line.
[][]Collect hot water from hot water mark water line.
[][]Use Pharma grade container to collect hot water for cleaning purpose.
[][]Transfer hot water to the respective production area by using SS trolley.

Purified Water

[][]Before Collection of purified water from the main re-circulation loop of purified water, connect the pipe with 50 Liter storage tank and main loop.
[][]Collect the purified water into the storage tank by turning the valve open.
[][]Circulate the water through the sectional circulation loop for 5 minutes and drain through use points and storage tank outlet.
[][]Transfer purified water to the respective production area by using SS trolley.
[][]After completion of work, disconnect the pipe between the pipe storage tank and main circulating loop and hang the pipe on the hanger.
[][]Keep both ends close with Alu foil after drain out of remaining water from pipe at the end of the day work

Water Handling System at the Production Premises Read More »

Rework Residue Handling Procedure

Rework Residue , Purpose:

Rework Residue , To lay down a procedure for Handling of Rework Residues from Batch Processed Material /Intermediate product.

Rework Residue , Scope:

This SOP is applicable for the Production Area of XX  Pharmaceuticals Limited.

Definition / Abbreviation:

[][]N/A

Responsibilities:

[][]The Roles and Responsibilities are as follows :

Operator

[][]To follow the laid down procedure.

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Manager, Quality Assurance

[][]To approve the Document.

Procedure:

Precaution:

[][]Do not add any rework unless it is authorized beforehand by Head of Quality Assurance.
[][]Do not add the rework of a batch to other batch (es) until packing of the batch is completed.
[][]Ensure that rework of different products is not stored in the same container.
[][]Do not store any rework which is less than 0.25 % of the actual batch size.

Rework Residue :

[][]Following stated defects can be considered for storage and addition as rework in a batch leftover granules, chipping / capping defects, lamination, tablets with variations in physical parameters like weight, hardness, thickness, friability or edge broken tablets at the time of compression, coating and inspection. Residue after compression, encapsulation & PFS is also be considered as rework.
[][]Prepare a ‘Rework Residue Addition Note’ as per format (Annexure-I). The rework addition note shall be approved beforehand by Head of Production or his designate and authorized by Head of Quality Assurance.

[][]Process the rework as per Batch Manufacturing Record (BMR) of the specific product from the declared necessary step(s).
[][]Maximum allowable amount for addition of rework in a fresh batch is 5 % of actual batch size.
[][]Rework bulk shall be free from any foreign matter, objectionable color and / or odor.
[][]First batch of any product in which rework is added shall be kept for stability study.

Non-Rework :

[][]Any amount of tablets / capsule(s) which is collected as ‘Rework’ but is less than 0.25 % of the actual batch size shall be considered as ‘non-rework’.
[][]‘Non-rework’ shall be destroyed as per Quality Assurance SOP.

Storage of Rework :

[][]Store the rework in tightly closed double lined polybag with “REWORK’ Label in a container on a pallet in WIP Tablet/Capsule store.
[][]Rework of more than one batch of the same product can be stored in one container with proper status label.
[][]Record the rework generated from the batch(es) and their addition history in ‘Rework Residue
[][]Register’ as per (Annexure II). The register shall be kept in production Executive.
[][]Issue rework residues for use only in the presence of Production Executive.
[][]Rework generated from a batch shall be added to the batch(es) which are manufactured within the next three months. For example, rework generated from a batch manufactured in January shall be added to only the fresh batch manufactured within April, not to be added to the batch manufactured in May and so on. But in that case expiry of the fresh batch where rework is added shall be same as expiry of rework batch. In such cases rework shall not be stored for more than 90 days. If any rework amount is left after the said period, destroy the left over with prior approval of Quality Assurance (QA).

Annexure:

Annexure I – Rework Reside Addition Note.
Annexure II – Rework Residue Register.

Rework Residue Handling Procedure Read More »

Additional Materials Return procedure to Warehouse

Additional Materials Return procedure, Purpose:

Additional Materials Return procedure, To lay down the procedure for return of Additional Part of Raw (Excipient) and Primary Packaging materials to Ware-House.

Additional Materials Return procedure, Scope:

This SOP is applicable for the Production Area  of the XX Pharmaceuticals Limited.

Definition / Abbreviation:

[][]N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows :

Operator

[][]To follow the laid down procedure.

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Manager, Quality Assurance

[][]To approve the Document.

Procedure:

Precaution:

[][]Ensure weighing and counting of the materials is correct.
[][]Returning of Unused Raw Materials (Excipient)
[][]After dispensing unused Raw Material (Excipient) can return to store.
[][]Enter all the details like Product Name, Batch No., Batch size, Name of the material, Quantity to be returned, Material ID No., Lab. Control No. on the ‘Stock Return Note’ (Annexure – I).
[][]Operator shall mention all details in Stock Return Note (SRN) and Executive, Production shall check all of them accordingly.
[][]The SRN shall have triplicate copy. All the copies shall be moved along with the physical stock to the Ware-House and Executive / In-charge, Ware-House shall return the rest 02 (Two) copies to the Packaging after duly signed. One copy shall attach with Batch Manufacturing Record and third copy shall retain in the book as reference copy.

[][]Returning of Unused Primary Packaging Materials
[][]After dispensing unused Primary Packaging Material can return to store.
[][]Individual rolls of Aluminum foil, PVDC and Alu bottom film which is return shall weigh and glass bottle, stopper and Alu cap shall count.
[][]Enter all the details like Product Name, Batch No., Batch size, Name of the material, Quantity to be returned, Material ID No., Lab. Control No. on the ‘Stock Return Note’ (Annexure – I).
[][]Operator shall mention all details in Stock Return Note (SRN) and Executive, Production shall check all of them accordingly.

[][]The SRN shall have triplicate copy. All the copies shall be moved along with the physical stock to the Ware-House and Executive / In-charge, Ware-House shall return the rest 02 (Two) copies to the Packaging after duly signed. One copy shall attach with Batch Manufacturing Record and another copy shall retain in the book as reference copy.

Returning of Raw Materials (Excipient) / Primary Packaging Materials Rejecting Online

[][]When the raw materials (excipient) / primary packaging materials are observe to be defective on-line such as having lumps or foreign materials in case of raw materials (excipient) and sealing problem or pinholes in case of foils keep aside the material.
[][]On line rejected material shall return to warehouse as per handling of on line rejection guideline of QA.

Annexure:

Annexure I – Stock Return Note.

Additional Materials Return procedure to Warehouse Read More »

Machine Handling During Breakdown

Machine Handling, Purpose :

Machine Handling, To lay down the procedure for handling of machine during breakdown.

Machine Handling, Scope :

This SOP is applicable for the Production Area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]To follow the laid down procedure.

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Manager, Quality Assurance

[][]To approve the Document

Procedure:

Precaution :

[][]Ensure that proper safety instructions are followed.

Activities:

[][]Shut OFF the main switch of the electric connection.
[][]Inform working Exe. / Sr. Exe., Production about the break-down status of the machine and In-charge is needed to confirm the extent of break-down priority basis.
[][]After checking the nature of break-down, he will intimate Engineering department through ‘Maintenance Request Form’ ( Annexure – I ) Send it to the General Manager, Engineering or his nominee for immediate course of action.
[][]Put off others utility line immediately one by one, so that, the machine turns neutral.
[][]Collect all the processing materials / intermediates and also product into the air-tight container being available before break-down of the machine.
[][]Clean the machine surface and outside by the vacuum cleaner and also the lint free cloth.
[][]Display the label ‘Under Maintenance’ on the front side of the machine for declaring its status.
[][]Involve machine Operator(s) throughout the Maintenance Process for speed up the Engineering job.
[][]Record the total down time of the Machine in the ‘Equipment Log Book along with it’s cleaning for next processing.
[][]Inform Quality Compliance Personnel to verify the extent of machine cleaning for next processing.

Annexure:

Annexure I – Maintenance Request Form 

Machine Handling During Breakdown Read More »

Material Requisition Procedure to Ware-House

Material Requisition Procedure, Purpose:

Material Requisition Procedure, To lay down the procedure for raising Requisition of Material to the Ware-House.

Material Requisition Procedure, Scope:

This SOP is applicable for the Production Area  of the XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]N/A

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]To follow the laid down procedure

Executive, Production

[][]To monitor and check the laid down procedure

Manager, Production

[][]To Implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure:

[][]Material Requisition shall be raised in following cases.
[][]On line rejection: If approved raw material or packing material issued for the batch is rejected on line due to quality defects like black particles in raw material, hard lumps, smudged printing or no  printing on printed materials like foil, carton, insert, label and shipper and color variation beyond acceptable shade.
[][]Material consumed more than standard: In case dispensed raw material is compensated due to spillage, spray pipe leakage during coating, excess coating material and packaging materials required for recovery addition, excess foil consumption during blister pack machine setting, excess carton consumption during manual cartooning, printing problem of carton, catch cover, insert and shipper carton.
[][]Production Executive shall raise ‘Material Requisition’ (Annexure-I) by writing all details with reason in the ‘Remarks’ column and shall sign in ‘Requisitioned by’ row.
[][]Material Requisition (MR) shall have duplicate copy. First copy shall be mentioned as ‘Ware-House Copy’ at right top corner of Material Requisition form. Second copy shall be mentioned as ‘Batch Record Copy’ at right top corner of Material Requisition form.
[][]Head of Quality Assurance (QA) or his/her designate shall justify the reason for MR and will approve accordingly.
[][]Approved Material Requisition shall be sent to dispensing for Issuance.
[][]After Issuance of materials ‘Batch Record’ copy shall be attached with Batch Manufacturing Record (BMR) & Batch Packaging Record (BPR) and ‘Ware-House Copy’ shall be sent to Ware-House for stock adjustment purpose.

Annexure:

Annexure I –Material Requisition.

Material Requisition Procedure to Ware-House Read More »

Equipment Logbook, how to use it?

Equipment Logbook, Purpose:

Equipment Logbook, To lay down the procedure for Maintaining Record of Equipment Usage, break-down, cleaning and change over functions during all Manufacturing Activities.

Equipment Logbook, Scope:

This SOP is applicable for the Production Area of General Block of the XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]Equipment : The implement, which is used at an Operation or Activity.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]To follow the laid down procedure

Executive, Production

[][]To monitor and check laid down procedure

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure:

Use of Equipment Log Book :

[][]Equipment Log Book is to record equipment usage maintenance and cleaning record. The records are maintained to trace back the previous history.
[][]Maintain individual ‘Equipment Log Book’ (Annexure-I) for each equipment.
[][]Equipment log book format is divided in 05 parts
[][]Product Information
[][]Equipment usage details
[][]Cleaning details
[][]Change Over details
[][]Inspection and Approval
[][]Product Information
[][]Product name, Batch no., Batch size shall be recorded in log book.
[][]Each book is dedicated for each equipment
[][]Equipment usage details
[][]Product start time and end time shall be recorded in log book.
[][]This is applicable for each batch activity.
[][]Record the activity / batch operations shift wise in log book.

[][]All break times like Lunch time, Tea time, machine stoppage due to breakdown, machine stoppage at the end of the shift or day and machine stoppage due to power failure, only if restart time is more than 5 minutes.

Equipment cleaning details

[][]The equipment cleaning is applicable in following events.
[][]Batch changeover of the same product and different product.
[][]After cleaning if cleaned equipment is kept idle for more than defined hold time which shall be studied and incorporated in respective equipment SOP.
[][]If equipment is relocated /shifted within the facility as well as for new equipment.
[][]In case of cleaning after maintenance activity.
[][]In case of cleaning after area fumigation.
[][]After usage of equipment, clean it as per the procedure defined in respective equipment SOP.
[][]The type of cleaning shall be mentioned in specified column in log book.
[][]After cleaning is completed, inform QA (Quality Assurance) to inspect and approve for next activity.

Change Over Details :

[][]Change Over is applicable in following events.
[][]Change over is done for product to product change.
[][]Start and end time shall be mentioned in specified column in log book.
[][]After change over is completed, Executive, Production check setting of machine & will take step for next activity.

Inspection and Approval before usage

[][]Before usage Equipment, it is to be checked for its suitability for next activity by Executive, Production and then inspected and approved by Executive, Quality Compliance.
If production is on campaign basis, after every 10th batch, cleaning activity is carried out and details are recorded.
[][]During campaign of same product, equipment shall be cleaned as per respective equipment SOP but prior to start next batch approval shall be taken by Executive, Quality Compliance.

Additional Information at the Remarks Column

[][]Throughout the working day operation, if the operating machine turns ‘Stop’ by either mechanical or electrical reasons, note the total down time for a day at the Remarks column.

Annexure:

Annexure I – Equipment Log Book.

Equipment Logbook, how to use it? Read More »

Micro-dose Dilution Technique for the low API content products

Micro-dose Dilution Technique, Purpose:

Micro-dose Dilution Technique, To ensure the confirmation of content uniformity of the lower quantity of Active Pharmaceuticals Ingredient (lower than 10 mg per unit) presents in the selective products of the XX pharmaceuticals Limited.

Micro-dose Dilution Technique, Scope:

This SOP is applicable for the selective products (API content less tha10 mg per unit) processes at the
Production Unit of the XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]Micro-Dose: Smaller quantity with respect to the Processing Batch Size.
[][]BMR: Batch Manufacturing Record.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Machine Operator

[][]To follow the laid down procedure.

Executive, Product Development

[][]To establish the steps of dilution as parts of total mixing

Executive, Production

[][]To monitor the steps of dilution as parts with described timeline throughout the Mixing Process.

Manager, Production

[][]To implement this correctly.

Manager, Quality Assurance

[][]To approve the Document.

Annexure:

N/A.

Procedures:

Precautions:

[][]To check all the Materials for the involved batch must be available at the beginning of the process.
[][]First sort out the Active Pharmaceutical Ingredient (API) and excipients from the supplied batch materials.
[][]Divide the API(s) to make them three parts.
[][]First step
[][]Take one third of API (1st part of API) and equal quantity of excipients in a poly bag.
[][]Mix them for 3-5 minutes.(premix-1)
[][]Take premix-1 and equal quantity of excipients (Filler) in the poly bag.
[][]Mix them for 3-5 minutes. (premix-2)
[][]Take premix-2 and equal quantity of excipients (Filler) in the poly bag.
[][]Mix them for 3-5 minutes. (premix-3)
[][]Second Step: Repeat the same process  for the second part of API
[][]Third Step: Repeat the same process for the third part of API
[][]Mix first, second and third part of premix respectively for 2-3 minutes clockwise manually.
[][]Calculate the active premix from step  into two part A & B.
[][]Take the remaining excipients of batch quantity and pass through Vibratory Sifter or manually sieve.
[][]Then take part A of active premix into Vibratory Sifter.
[][]Take the remaining excipients of 2nd part  & pass through Vibratory Sifter or manually sieve.
[][]Then take part B and pass through the Vibratory Sifter or manually sieve.
[][]Now take all the parts to the Cone Blender.
[][]Seal the Cone Blender with its upper part & start dry mixing all the parts as a whole for up to 30 minutes.
[][]Stop the Cone Blender and allow the In-Process Quality Compliance (IPQC) Person to take the required quantity of sample for checking the content uniformity of the Micro-Dose API as of the calculation basis.
[][]If the IPQC person declares the dry mixing status satisfactory, then start the next process as mentioned in the BMR.
[][]If the dry mixing status found unsatisfactory, then go for Cone Blender operation for another 15 minutes. Then follow  as mentioned above satisfactory for the next process.
[][]Proceed for next operation as per the BMR.

Micro-dose Dilution Technique for the low API content products Read More »

Line Clearance at Production Area

Line Clearance , Purpose:

Line Clearance , To lay down the procedure for Line Clearance at Production Area during Product to Product changeover and Batch to Batch changeover.

Line Clearance , Scope:

This SOP is applicable for the Production Area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]To follow the laid down procedure.

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document.

Procedure:

Precautions:

[][]Ensure the proper safety instructions are followed.
[][]Ensure that no previous product is available in the area.

Line Clearance during Product to Product Changeover

[][]Ensure that all utility lines like compressed air line, steam line, electrical fixtures, air inlet ducts, return air risers, potable water and purified water lines are cleaned and no visible traces of product are present.
[][]Ensure that door, floor, walls and ceiling are cleaned.
[][]Ensure that area cleaning activity is recorded in ‘Room Cleaning Log book’
[][]Ensure that all equipments in the area are cleaned according to their respective SOPs and no traces of previous product are visible within the equipment.
[][]Check and ensure that equipment cleaning activity is recorded in respective ‘Equipment Log Book’
[][]Ensure that Span between equipment usage and cleaning is not more than seventy two hours.
[][]Ensure that Balances in the production area are cleaned and accuracy check is done once daily.
[][]Ensure that production utensils like scoops, spatula, pallets, BMR table, tool boxes etc. are cleaned as per procedure.
[][]Ensure that all equipments are labeled as ‘CLEANED’
[][]Ensure that fresh set of gowns are issued to concerned operators.
[][]Ensure that proper environmental condition is maintained in the area and the records of the same are maintained in the specified formats.
[][]Ensure the correctness of Batch Manufacturing Record / Batch Packaging Record.

Line Clearance during Batch to Batch Changeover

[][]Ensure that previous batch material is removed from the production area.
[][]Ensure that all the equipment and their spares are cleaned according to their respective SOPs.
[][]Ensure that equipment cleaning activity is recorded in respective ‘Equipment Log Book’.
[][]Ensure that floor is cleaned using vacuum cleaner and no visible traces of the previous batch material on the floor.

Annexure:

[][]N/A

Line Clearance at Production Area Read More »

Raw & Primary Packaging Materials Dispensing

Raw & Primary Packaging Materials, Purpose:

Raw & Primary Packaging Materials, To lay down the procedure for Dispensing of Raw and Primary Packaging Materials used for Manufacturing of Products.

Raw & Primary Packaging Materials, Scope:

This SOP is applicable for the Production Area of General Block of the XX Pharmaceuticals Limited.

Definitions / Abbreviation:

Dispensing: To Prepare and Distribute Medicine.

Responsibilities:

[][]The Roles and Responsibilities are as follows :

Operator

[][]To follow the laid down procedure

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Annexure:

[][]N/A.

Procedure:

Precautions:

[][]Ensure the cleanliness of Dispensing Area, Weighing Balances, Dispensing Booth, Waste Bin, Pallets before commencing the dispensing activity.
[][]Ensure that Balances are Calibrated and checked for daily accuracy.
[][]Ensure that Dispensing Booth should be switched ‘ON’ 30 minutes before starting dispensing activity.
[][]Ensure that Pressure Differential, Temperature and Relative Humidity of Raw Material (RM) Store, Dispensing and Post Dispensing area are within the specified range. Record details of the same in specified log books.
[][]Executive, Production should obtain Line Clearance from Executive, In-Process Quality Control(IPQC) before dispensing of Batch.
[][]Use separate scoop / spoon for Active Pharmaceutical Ingredient (API) & excipients.
[][]Use hand gloves, mask and eye protector (if required) during weighing and handling of materials.

Dispensing of Raw & Primary Packaging Materials:

[][]Production Personnel shall send the Bill of Material (BOM) along with Batch Manufacturing Record & Batch Packaging Record of respective batch / batches of Product to dispensing unit for dispensing of Raw & Primary Packaging Materials 24 hours in advance.
[][]Upon receipt of BOM Production Personnel shall calculate the quantity of active material for a batch on the basis of potency and other excipient as required.

[][]Operator shall arrange to transfer the required materials from RM & PM Store to ‘Material Staging’ through Air lock corridor.

Material Entry to Dispensing Booth:

[][]Dispensing operator will bring raw materials from ‘Material Staging Area’ to Dispensing Booth through material entry one by one.
[][]Only one raw material shall be dispensed at a time.
[][]Excipients shall be dispensed first and then Active Pharmaceuticals Ingredients (API).

Man Entry to Dispensing Booth:

[][]Dispensing execution team, Executive Quality Compliance, Executive Production and Production Operator will enter in the Dispensing booth through man entry with proper gowning.
[][]Operator shall take the required number of clean and dried Stainless Steel (SS) Scoops/Spatula/ Spoon for dispensing of materials.

Dispensing of Raw Materials :

[][]Obtain Line Clearance approval from Executive, Quality Compliance before starting the dispensing activity.
[][]Operator shall check status labels affixed on the container & simultaneously checked by Executive, Production and Executive, Quality Compliance.
[][]Keep the clean container/drum & polybag in the room.
[][]Fresh double polybags shall be used for holding dispensed materials.
[][]In case of spillage of any raw material during dispensing, collect and weigh the quantity of spillage and destroy.
[][]During weighing of each material, ensure zero on weighing scale before proceeding for dispensing.
[][]Weight the empty Polybag and tare the weight by pressing ‘Tare’ button. Then record in ‘MATERIAL DISPENSING SLIP’

[][]Loose container/ bag should be taken first for dispensing.
[][]Transfer the required quantity of material into tare polybag as per BOM and record the weight in ‘MATERIAL DISPENSING SLIP’.
[][]Remove the issued material of polybag from the weighing balance and keep them on the respective material holding SS Cage Trolley.
[][]After completion of weighing of all materials transfer into the ‘Dispensed Material Staging’ Area & keep the room locked.
[][]In case any quantity of the material is left in original container / bag, affix ‘LOOSE LABEL’  on container/bag.
[][]Keep the Loose bags or containers in ‘Broken Bulk’ room. Send back them to RM Store through Airlock corridor except active material.
[][]At the time of Dispensing, Operator shall fill the details of each dispensed material in the BOM and simultaneously cross checked by Executive, Production and Executive, Quality Compliance.
[][]Dispensing operator shall prepare ‘MATERIAL DISPENSING SLIP’ for each dispensed Materials and which shall be simultaneously checked by Executive, Production and verified by Executive, QA.
[][]Operator shall sign in the column marked as ‘Dispensed by’ in BOM after issue of each and every raw material at the time of dispensing.
[][]Executive, Production shall sign in the column marked as ‘Checked by’ in BOM against each and every raw material.
[][]Executive, Quality Compliance shall sign in the column marked as ‘Checked by’ in BOM against each and every raw material.
[][]In case of any adverse observation, report to Executive, In-Process Quality Compliance (IPQC) for corrective action.
[][]Deface all the labels of empty containers / polybags / boxes / plastic tie with cross marking and transfer them to the scrap area through designated route.

[][]On completion of Dispensing, clean the dispensing area, booth, balances, and utensils as per respective cleaning procedures & record the same in log book. Hang the status label ‘CLEANED’  outside the door.

Dispensing of Primary Packaging Materials :

[][]Obtain Line Clearance approval from Executive, Quality Compliance before starting the dispensing activity.
[][]Operator shall bring required primary packaging materials from ‘Material Staging Area’ and transfer them one by one to dispensing area.
[][]Operator shall check status labels affixed on the container & simultaneously checked by Executive, Production and Executive, Quality Compliance.
[][]In case of spillage of any primary packaging material during dispensing, collect and weigh the quantity of spillage and destroy.
[][]During weighing of each material, ensure zero on weighing scale before proceeding for dispensing.
[][]Weight the empty Polybag and tare the weight by pressing ‘Tare’ button. Then record in ‘MATERIAL DISPENSING SLIP’.
[][]Loose container/ bag should be taken first for dispensing.
[][]Transfer the required quantity of material into tare polybag as per BOM and record the weight in ‘MATERIAL DISPENSING SLIP’.
[][]Remove the issued material from the weighing balance and keep them on the respective material holding SS Cage Trolley.
[][]After completion of weighing of all materials transfer into the ‘Dispensed Material Staging’ Area & keep the room locked.
[][]In case any quantity of the material is left in original container / bag, affix ‘LOOSE LABEL’ on container/bag.
[][]Keep the Loose bags or containers in ‘Broken Bulk’ room. Send back them to PM Store through Airlock corridor.
[][]At the time of Dispensing, Operator shall fill the details of each dispensed material in the BOM and simultaneously cross checked by Executive, Production and Executive, Quality
Assurance
[][]Operator shall prepare ‘MATERIAL DISPENSING SLIP’ for each dispensed Materials and which shall be simultaneously checked by Executive, Production and verified by Executive, QA
[][]Operator shall sign in the column marked as ‘Dispensed by’ in BOM after issue of each and every primary packaging material at the time of dispensing.
[][]Executive, Production shall sign in the column marked as ‘Checked by’ in BOM against each and every primary packaging material.
[][]Executive, Quality Assurance  shall sign in the column marked as ‘Checked by’ in BOM against each and every primary packaging material.
[][]In case of any adverse observation, report to Executive, Assurance for corrective action.
[][]Deface all the labels of empty containers / polybags / boxes with cross marking and transfer them to the scrap area through designated route.
[][]On completion of Dispensing, clean the dispensing area, booth and balances as per respective cleaning procedures & record the same in log book. Hang the status label ‘CLEANED’ outside the door.

Raw & Primary Packaging Materials Dispensing Read More »

Digital Weighing Balance Operation, Cleaning at Production Area

Digital Weighing Balance, Purpose:

Digital Weighing Balance, To lay down the procedure for operation, accuracy check and cleaning of the weighing balances at the Production Area.

Digital Weighing Balance, Scope:

This SOP is applicable for 320 g & 60 Kg weighing balance for weighing of materials at the Production Area of XX Pharmaceuticals Ltd.

Definition / Abbreviation:

N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]To follow the laid down procedure

Executive, Production

[][]To monitor and check the cleanliness of area

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure:

Precaution:

[][]Do not pour liquids on the weighing platform.
[][]Do not use solvents to clean the platform.
[][]Ensure balance is clean before use, including its surrounding area.
[][]Check and ensure the due date of calibration before use.
[][]Check and ensure the level indicator of weighing balance is in the middle, if applicable.
[][]Use hand gloves to hold standard weights for function check and calibration.

Daily Performance Check :

[][]Plug in the power cord.
[][]Level the balance using leveling feet so that air bubble is centered within circle of level indicator.
[][]TO turn the balance ON, short pressing the <O/T> key.
[][]Wait a while so that the stability indicator [*] is displayed.
[][]Zero the balance by pressing the >O/T> key.
[][]Press the 100 mg mass at the centre of the platform and record the value displayed in the daily balance check logbook.
[][]Press the 100 g mass at the centre of the platform and record the value displayed.
[][]Press the 200 g mass at the centre of the platform and record the value displayed.
[][]Print the results by pressing print ( ) button if necessary.
[][]Record the value of those weights in Log Book for ‘Daily Accuracy Check’ (Annexure – I).
[][]If any displayed value is out of acceptable limit, label the balance “DO Not Use” and inform the QA Executive for immediate calibration of the balance.
[][]Balance accuracy check must be performed at the starting of the day.

[][]If the factory remains close for the day(s), put the comments in the remarks column against that day(s) at the day of factory resume.

Operation of 320 g Balances of Mettler Toledo :

To start up:

[][]Level and adjust at each time it is moved to a new location. The balance is exactly horizontal when the air bubble is in the middle of the level glass. Adjust the two front leveling feet appropriately until the air bubble comes to rest exactly in the middle of the glass.
[][]Plug the AC adapter and connect the power supply. Connect the printer to the balance (if available).
[][]Switch on the printer using I/O switch.
[][]Press On/Off ( ) button to on the Electric Analytical Balance. Display will show 0.000g.
[][]Convert the weighing unit from g into mg, press scroll down ( ) button if necessary.
[][]Allow the balance to warm up to enable it to adapt itself to the ambient condition.
[][]Long press for menu ( ) button and select ‘BASIC’ by single press Enter button ( ).
[][]Set date, time and unit using – /+ keys and Enter button ( ) and save the settings using ( ) button.
[][]Press cancel (C) button to return come out of that ‘BASIC’ option and return to its main menu.

[][]Perform the ‘Daily Accuracy Check’ (Annexure – I) at the starting of the day.

Weighing:

[][]Check the machine is clean and calibrated. Then remove all loads from weighing pan.
[][]When zero (0.000 g) reading is displayed, the balance is ready for operation. If the display shows greater than or less than zero, press tare ( O/T ) button to tare the balance.
[][]If the balance is not in the weighing mode, press and hold the ( ) key down until ‘WEIGHING’ in the display.

[][]Use handle/coupling element for the operation of the draft shield door of the both side of the instrument.
[][]Open right/left/upper sliding window of the instrument.
[][]Place empty container/weighing paper on the pan of the balance. Close the sliding window.
[][]The weight is displayed. Allow the reading to stabilize and wait until the instability detector (O) disappears from the left side of the display and the stability beep sounds.
[][]Press tare ( O/T ) button to tare the balance. When zero (0.000 g) reading is displayed, the balance is ready for weighing.
[][]The weighing-in aid is a dynamic graphic indicator which shows the used amount of the total weighing range. It can be recognized at a glance when the load on the balance approaches the maximum load.
[][]Add weighing sample (Maximum 320g) on the container/weighing paper using weighing spoon. Close the sliding window. The net weight is now displayed.
[][]Allow the reading to stabilize and wait until the instability detector (O) disappears for the display and the stability beep sounds.
[][]To get printout of the weight, press print ( ) button.

[][]For performing another weighing press tare ( O/T ) button to tare the balance and follow steps from previous steps To increase or decrease digit, press display resolution ( ) button.
[][]Finally, press and hold On/Off button ( ) button until ‘SHUT OFF’ shows on the display.

Calibration:

Internal Calibration:

[][]Manual Adjustment with Internal weight:
[][]Long press menu ( ) button and press scroll down ( ) button to go to ‘ADVANCED’ option.
[][]Select ‘ADVANCED’ by pressing Enter ( ) button.
[][]Press scroll down ( ) button once to select ‘CAL’ option by pressing Enter ( ) button.
[][]Then select ‘ADJ. INT’ using scroll down ( ) button and then press Enter ( ) button.
[][]Press cancel (C) twice and save the settings if required by scrolling down ( ) button and press Enter ( ) button and then return to its main menu.
[][]Unload weighing pan Press and hold calibration ( ) button to execute ‘Internal Adjustment’.
[][]The balance adjusts itself automatically. The adjusting is finished when the message “ADJ.DONE” appears briefly on the display. The balance returns to the last active application and is ready for operation.

[][]After adjustment, the result of the calibration will be printed out automatically or press print ( ) button for print copy.

External Calibration:

[][]Manual Adjustment with External weight:
[][]Follow the instruction from previous steps
[][]Select ‘ADJ. EXT’ by using scroll down ( ) and then press Enter ( ) button.
[][]Set the adjustment weight (100g) by using -/+ key for External Calibration and press Enter ( ) button.

[][]Then press cancel (C) button twice and save the settings if required by using -/+ key and press Enter ( ) button and then return to its main menu.
[][]Unload weighing pan Press and hold calibration ( ) button to execute ‘External Adjustment’.
[][]The required predefined adjustment weight value flashes on the display.
[][]Place adjustment certified weight on the center of pan. The balance adjusts itself automatically.
[][]When ‘0.00 g’ flashes, remove the adjustment weight.
[][]The adjustment is finished when the message ‘ADJ DONE’ appears briefly on the display. The balance returns to the last active application and is ready for operation.
[][]After adjustment, the result of the calibration will be printed out automatically or press print ( ) button for print copy.

Operation of 60 kg Balances of Mettler Toledo:

[][]Using an Empty container for Weighing:
[][]Press the zero button.
[][]Place an empty container on the scale platform.
[][]Press the Tare button.
[][]Fill the container with material to be weighed.

[][]The terminal will display the net weight and the NET cursor will light up. Allow the reading to be stable. Write down the reading.
[][]To clear a tare weight (with the scale in the net weight mode and a tare weight previously entered), press the Clear key (C).

Without using an Empty container for Weighing:

[][]Press the zero button.
[][]Place the material to be weighed on the scale platform.
[][]The terminal will display the net weight and the NET cursor will light up. Allow the reading to be stable. Write down the reading.
[][]Perform the ‘Daily Accuracy Check’ (Annexure – I) at the starting of the day.

Acceptance Criteria:

[][]The observed weights should be within ± 0.1% of the certified standard weights.
[][]If the acceptance criteria are not satisfied, follow the procedure for Handling of out of calibration for instrument & equipment.

Calibration:

[][]Perform the routine calibration half year. Recalibration is required in the following cases :
[][]After any minor service has been done or replacement of parts.
[][]When the software or firmware has been upgraded or changed.
[][]If daily check fails

Cleaning:

[][]Place the status label ‘TO BE CLEANED’  on the equipment.
[][]Switch off the balance and unplug from the socket.
[][]Remove all objects from the weighing platform of balance.
[][]Lift up and remove the weighing pan in such a way that there is no damage in weighing system.
[][]Clean the pan including underside using a piece of dry cloth. Use wet cloth and finally clean with disinfection solution
[][]Wipe the display, switch board and cables with dry cloth.
[][]Remove ‘TO BE CLEANED’ and affix ‘CLEANED’  label on the equipment after approval from Quality Compliance.
[][]Record the cleaning parameters on the ‘Equipment Log Book’

Annexure: Digital Weighing Balance

Annexure I – Daily Accuracy Check.

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Monitoring of Room Condition at Production Area.

Monitoring of Room Condition, Purpose:

Monitoring of Room Condition, To lay down the procedure for monitoring of Temperature, Relative Humidity (%) and Pressure Gradient at the Production Area.

Monitoring of Room Condition, Scope:

This SOP is applicable for the Production Area of General Block of the XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows :

Operator

[][]To follow the laid down procedure

Executive, Production

[][]To monitor and check the procedure is followed

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure :

Precaution :

[][]Do not use a new hygrometer unless it is calibrated.
[][]When any hygrometer is shifted from one location to another, allow to stabilize the device prior to record the temperature / Relative Humidity (%).
[][]Check the due date of calibration of the hygrometer and magnehelic gauge before taking reading.
[][]Ensure that temperature and Relative Humidity (%) readings are taken before going to operation.

[][]Temperature and Relative Humidity (%) (using Digital Hygrometer)
[][]Ensure that no dust is accumulated over the sensor.
[][]Read the temperature and relative humidity (%) values displayed on the screen of digital/analog hygrometer and record in ‘Temperature, Relative Humidity (%) & Pressure Gradient Records’ (Annexure-I).
[][]Acceptance Criteria:

AreaTemperatureRelative Humidity (%)
Dispensing, Material Staging, Dispensed Material Staging, D Corridor, Wash Bay, Clean Equipment, Broken Bulk, FBD Bag Store, Solution Preparation, Clean Equipment, Encapsulation, WIP Granules, WIP Tablet & Capsules, Coating, Tools Storage, Office Room, Coating Solution Preparation, D Dress Washing & Drying, Foil/Film Staging, Blister Packaging and Dry Syrup Filling & Sealing.Not more than (NMT) 25°CNot more than (NMT) 60 %
Granulation, Blending, Tablet Compression.Not more than (NMT) 25°CNot more than (NMT) 45%

Pressure Gradient

[][]Read the pressure differential from magnehelic gauge provided and record.
[][]If the reading is not within limit, check whether all the doors are closed.
[][]Observe the second reading.
[][]Even if the second reading is not within the limit, inform the Engineering department for corrective action.

AreaPressure Differential
Processing Units
Negative with respect to corridor (i.e. Air Flow is from corridor to processing unit)
10 – 20 Pascal
Wash Bay
Positive with respect to Corridor (i.e. Air Flow is from Wash Bay to Corridor)
10 – 20 Pascal

Frequency

[][]Twice in a shift, first before starting the operation and second after four hours.
[][]If the reading is not within limit at any time of operation, inform the Engineering department immediately and take following steps in different areas.
[][]At Dispensing area stop weighing process, close the bags / high density polyethylene (HDPE) drums of raw materials.
[][]At Granulation area, stop transfer process of materials if running and close the SS / HDPE container with lid.
[][]Do not discharge if temperature and relative humidity (%) or pressure gradient are not within limit.
[][]At Blending area, continue blending process if already running.
[][]At Compression area, stop operation and close the tablet SS/HDPE container lid. Do not keep the granules in the hopper during overnight.
[][]Empty the hopper and close the lid of SS / HDPE container.
[][]At Encapsulation area, stop operation and close the capsule SS/HDPE container lid. Do not keep the granules / pellets in the hopper during overnight. Empty the hopper and close the lid of SS/ HDPE container.

[][]At Coating area, continue operation if already running, otherwise stop operation. Do not unload if temperature and relative humidity (%) or pressure gradient are not within limit.
[][]At Powder filling area, stop the operation. Do not keep the granules in the hopper during overnight.
[][]Empty the hopper and close the lid of SS / HDPE container.
[][]At Blister Packing area, close the lid of tablet / capsule container, close the hopper with lid and stop further operation.

Annexure:

Annexure I – Room Condition Monitoring Logbook

Monitoring of Room Condition at Production Area. Read More »

Utensils Cleaning & Storage for Production are & Dispensing

Utensils Cleaning & Storage, Purpose:

Utensils Cleaning & Storage, To lay down the procedure for Cleaning and Storage of Dispensing and Production Utensils.

Utensils Cleaning & Storage, Scope:

This SOP is applicable for the Production Area of  XX Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]To follow the laid down procedure

Executive, Production

[][]To monitor and check the laid down procedure

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Annexure:

[][]N/A.

Procedure:

Precaution :

[][]Do not clean/disinfect the area when the process is running.
[][]Do not touch the cleaned equipment/utensils without wearing hand gloves.
[][]Always store small items like dispensing scoop, spatula, spoon, mug etc. in polythene bags in
[][]closed condition in clean equipment store after cleaning
[][]If clean equipments/ utensils remain unused for more than three days or 72 hours clean them again before use.
[][]Unclean equipments/ utensils must be cleaned after completion of work on regular basis.

Cleaning Tools / Agents

[][]Cloth & wiper
[][]Potable water and Purified water
[][]Nylon brush

Cleaning of Utensils

[][]Place all unclean production utensils on a trolley or in a polythene bag and label it as
[][]‘TO BE CLEANED’ and transfer them to washing area for cleaning.
[][]First wiping with dry cloth to remove loose dust. Clean them using cloth and potable water. Use hot water and nylon brush if required.
[][]After cleaning with potable water, finally rinse them with purified water. Then wipe with clean lint free cotton cloth to remove water.
[][]After final cleaning let them drying by dryer.
[][]After drying take them separately in closed polythene bag and then keep them in an equipment
[][]cabinet & label with ‘CLEANED’  status label.
[][]Clean hoses/pipes first with potable water and cloth and finally with purified water. Use hot water if required. After cleaning wrap them with polythene. Removal of water then label as ‘CLEANED’status label.
[][]These cleaned items will directly be taken for processing purpose.
[][]Frequency of Cleaning
[][]During product to product change over.
[][]Dispensing scoop, spatula, spoon used in production area to be cleaned during batch to batch change over.

Cleaning of Containers (SS/HDPE)

[][]Clean the containers used for holding intermediate bulk products after each stages of manufacturing activities by following below mentioned procedure. For holding coated tablets, use the same containers holding compressed tablets after wiping with dry cloth to remove loose dust.
[][]Transfer unclean container with a label ‘TO BE CLEANED’ to washing area for cleaning.
[][]Clean the container and lid with dry cloth to remove loose dust then with potable water.
[][]Finally clean with purified water and wipe with clean lint free cloth to remove water.
[][]Remove the ‘TO BE CLEANED’ label and label as ‘CLEANED’ status label.
[][]Frequency of Cleaning
[][]During product to product change over.
[][]Dry clean during batch to batch change over.

Utensils Cleaning & Storage for Production are & Dispensing Read More »

Production area Cleaning Procedure

Production area Cleaning Procedure, Purpose:

Production area Cleaning Procedure, To lay down the procedure for effective Cleaning of Production area during Product to Product change over, Batch to Batch change over and at the end of day’s operation.

Production area Cleaning Procedure, Scope:

This SOP is applicable for the Production Area of  XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]To follow the laid down procedure

Executive, Production

[][]To monitor and check the cleanliness of area

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure:

Precaution :

[][]Do not clean/disinfect the area when the process is running.
[][]Keep the cleaning agents at the designated place only with proper labels.
[][]Ensure that after usage the wet mops are washed and hanged in hanger in cleaner store &allowed to dry. Ensure other cleaning tools are also hanged in hanger after use.
[][]After use of cleaning agent wash hands, feet and fingers thoroughly with soap & plenty of water.
[][]Ensure that during cleaning all the product containers are closed.
[][]Check and ensure that disinfectant solution prepared is not stored for use for the next day and the residue is discarded by pouring into drain.
[][]At least two different disinfectants are to be used alternatively on weekly basis.
[][]Do not mop the floor after keeping ‘Cleaned’ equipment in clean equipment storage room.

Cleaning Tools / Agents

[][]Portable vacuum cleaner
[][]Cloth & wiper
[][]Potable water and Purified water
[][]Glass Cleaning agent: ‘Clear View’ (Brand Name)
[][]Disinfectant Savlon (Cetrimide + Chlorhexidine Gluconate) / Dettol (Chloroxylenol) / Clotec (Hypochloride).

Preparation of 2.5 % v/v Savlon/ Dettol/Clotec

[][]To make 10 L disinfectant solution take 0.250 L Cetrimide + Chlorhexidine Gluconate/ Chloroxylenol / Hypochloride in freshly collected purified water to make up volume up to 10 L.
[][]Stir well to mix the solution properly.
[][]Prepare the disinfectant solution separately in separate bucket for use in different floor.
[][]Maintain the ‘Disinfectant Solution Preparation Record’ (Annexure – I).

Product to Product Cleaning Procedure (Type – A Cleaning) for Production Area

[][]Type – A cleaning is defined as cleaning procedure followed during product to product changeover.
[][]If the unit/equipment is used for same product it has to be cleaned after 72 hours.
[][]Place the status label ‘TO BE CLEANED’ (As per Form No. SOP/QCOM/008/XI) in the Area.
[][]Clean the ceiling, walls, outer surface of light fixtures, supply diffusers (SD) and return grills (RG) first with portable Vacuum cleaner to remove loose dust using a platform trolley, then with wet mop.
[][]Clean the machine/equipment in Production area as per SOP.
[][]Clean the doors, compressed air lines and other service lines with dry cloth.
[][]Clean the glasses with ‘Clear View’ solution and wipe.
[][]Clean the control panels, electrical wires with dry cloth.
[][]Clean toolbox, Batch Manufacturing Record table, log books, SOP holders, hygrometer, stool / chair with dry cloth.
[][]Clean the floor first with dry mop, then with potable water and mop with disinfectant solution. Finally clean with purified water.
[][]Ensure after inspection for absence of any residue of previous product. If any residue of previous product or extraneous matter is found, re-clean the area using above procedure until the area is free of any residue/ extraneous matter.

[][]Remove ‘TO BE CLEANED’ and affix ‘CLEANED’ (As per Form No. SOP/QCOM/008/IX) label in the cleaned area after approval from Quality Compliance.
[][]Record the cleaning activity in ‘Room Cleaning Log Book’ (Annexure – II).

Frequency of Cleaning

[][]During product to product change over.
[][]After 3 days or 72 hours from the date of use of the equipment or area. If any batch is running and 72 hours time exceeds during the batch running period, cleaning shall be done after the batch is finished. If 72 hours time exceeds after cleaning and the equipment or area is not used, use the equipment or area after performing B-type cleaning.

Batch to Batch Cleaning (Type-B Cleaning) for Production area

[][]Type – B cleaning is defined as cleaning procedure followed during batch to batch changeover of a
same product.
[][]Place the equipment status label ‘PARTIALLY CLEANED’ (As per Form No. SOP/QCOM/008/X) in the area.
[][]First clean the floor, ceiling, walls, outer surface of light fixtures, supply diffusers (SD), return grills, (RG) doors and equipment with portable vacuum cleaner to remove the loose dust. [][]Finally clean the floor with wet mop.
[][]Remove ‘PARTIALLY CLEANED’ and affix ‘CLEANED’ (As per Form No. SOP/QCOM/008/IX) label in the area.
[][]Record the cleaning activity in Room Cleaning Log Book.
[][]Frequency of Cleaning
[][]During batch to batch change over

[][]Cleaning at the End of Day’s Operation
[][]Clean external parts of the machine, and operating panel with dry cloth.
[][]Clean the floor first with dry mop, then with potable water and mop with disinfectant solution. Finally clean with purified water.

Annexure:

Annexure I – Disinfectant Solution Preparation Record.
Annexure II – Room Cleaning Log Book.

Production area Cleaning Procedure Read More »

Calibration of Friability Tester With Operation & Cleaning

Calibration of Friability Tester, Purpose :

Calibration of Friability Tester, The purpose of this SOP (Standard Operating Procedure) is to describe the operation, calibration and cleaning of friability tester.

Calibration of Friability Tester, Scope :

This procedure is applicable for friability tester (Model: Electrolab, EF-1W ) used in Product Development Laboratory of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]PD: Product Development

Responsibilities:

[][]The roles and responsibility is as follows:

Executive, PD

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Sr.Executive, PD

[][]To ensure that this procedure is kept up to date.
[][]To arrange training on the SOP to all concerned personnel.
[][]To ensure implementation of the SOP after training.

Manager, Quality Assurance

[][]Approval of the SOP.

Procedure:

Precaution(s):

[][]Make sure the knob is properly fitted on the shaft to assure the drum is held in position.
[][]Do not hold the drum while they are rotating.
[][]Do not use abrasive, aggressive material or solvents to clean the drum and the tray. If required use mild detergent.
[][]Do not use wet drum. Make sure the drum is dry when in use.
[][]Replace the fuse with the correct rating whenever required.

Operating Procedure:

[][]Turn on the power switch of Friabilator.
[][]After power on, the drum would initialise itself to the loading position and the instrument will initialise the weighing scale and the following display will be shown:

ELECTROLAB
EF 1 W FRIABILATOR

[][]The instrument is then ready for the setting of test parameter and to run the test and following display will be shown on the screen:

ELECTROLAB EF 1 W
SET = menu, START = run
[][]Press SET key to set the test parameter as the following way.
[][]The first parameter for the test is MODE selection. Select the Time or Count mode using the MODE key on the front panel. The desired value for the selected mode can be set using or & DIGIT SCROLL keys. Set Count 100 and Time 4 minutes. Press the ENTER key to go to the next parameter.
[][]The next parameter is RPM setting. The desired value from 20 RPM to 50 RPM can be set using the key or and DIGIT SCROLL keys. Set 25 RPM. Press the ENTER key to go the next parameter.
[][]The next parameter is for drum selection. Using the or keys the Friability or the Abrasion drum can be selected. Select the Friability drum. Press the ENTER key to go the next parameter.
[][]The next parameter is for selecting the Scale Connection Option. This option can be enabled (Y) or disabled (N) using or key. If no printer is connected select disabled (N) mode. Press the ENTER key to go to the next parameter.
[][]The next menu is for Clock setting. The default setting for this menu would be the current time. The Time can be adjusted using or key & DIGIT SCROLL key. Press the ENTER key to go to the next parameter.
[][]The next menu is for Date setting. The default setting for this menu would be the current date. The Date can be adjusted using or key & DIGIT SCROLL key. Press the ENTER key to go to the next parameter.
[][]The next menu is for the selection of the option to the last test result. Select No (N) by using or key. Press the ENTER key to go to the next parameter.
[][]The next menu is for the Sound option. Select Yes (Y) using or key.
[][]Press the SET key to exit from the SET menu.
[][]After weighing the test samples as per specific Standard Test Procedure, slide them gently into the drum through the side slit and press START key, input the weight of tablets, press ENTER to run the test.
[][]After the test is over, the drum rotates in the reverse direction, discharging all the test samples into the tray located below the drum.

[][]The drum would now initialize itself to the loading position. Carefully slide the tray out and remove the loose dust from the test samples, i.e. deduct the test samples. After deducting weight the sample, input the weight of deducted tablets, press ENTER, % friability will be displayed on the screen.
[][]Press SET key for performing a new test.

Calibration procedure:

[][]Ensure that the instrument is clean before use, including surrounding area.
[][]Check and ensure due date of calibration.
[][]Switch ON the power supply.
[][]Set the time 4.0 minutes by selecting TIMER key and start the machine and calibrated stopwatch simultaneously.
[][]Note the actual time shown by a calibrated stopwatch.
[][]Take three such readings and calculate the mean time.
[][]Set 100 counts (rotation) by selecting COUNT key (some tablets may be placed into the drum for ease of counting) and start the instrument.
[][]Record the number of rotation.
[][]Take three such readings and calculate the mean of rotation per minute.
[][]Record the observations in the Calibration report (Annexure –II).
[][]After completion of calibration switch ‘OFF’ the main supply.
[][]After completion of the calibration activity, affix the duly filled and signed calibration status label on the instrument.
[][]Calibration Frequency: Every three-month ±07 days of due date and after maintenance job.

Cleaning procedure:

Remove the knob by pressing gray colored button and open the drum.
Clean the drum with suitable dry duster or cloth.
If required use water and dry in air.
Place the drum properly and replace the knob.

Annexure:

Annexure-I: Log Book Of Friability Tester.
Annexure-II: Calibration Report Of Friability Tester

Calibration of Friability Tester With Operation & Cleaning Read More »

Calibration of Moisture Analyzer with Operation, and Cleaning

Calibration of Moisture Analyzer, Purpose :

Calibration of Moisture Analyzer, The purpose of this SOP (Standard Operating Procedure) is to describe the operation, calibration and cleaning of Moisture Analyzer.

Calibration of Moisture Analyzer, Scope :

This procedure is applicable for Moisture Analyzer (Model: METTLER TOLEDO, MJ33) used in the Product Development of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A

Responsibilities:

The roles and responsibility is as follows:

Operator / Supervisor, Product Development

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Executive / Senior Executive, Product Development

[][]To ensure that this procedure is kept up to date.
[][]To arrange training on the SOP to all concerned personnel.
[][]To ensure implementation of the SOP after training.

Manager, Quality Assurance

[][]Approval of the SOP.

Procedure:

Precaution(s):

[][]Keep sufficient free space around the instrument to avoid heat accumulation and over- heating.
[][]Never cover, plugged, taped over or tampered with any way the vent over the sample.
[][]Do not place any combustible material on, under or next to the instrument during operation.
[][]Be very careful to touch sample, sampling pan, sampling pan holder and heating module just after the operation.

Operating Procedure:

[][]Switch on the main power. Instrument shows “OFF” in display.
[][]Press the “ON/OFF” key to switch the instrument on.
[][]The instrument performs a self-test. Wait until the display shown 0.000 g.

Temperature setting

[][]Press the temperature setting key
[][]In display temperature reading shall be blinking.
[][]Select the desire temperature by pressing scroll button
[][]Press enter key to conform the temperature.
[][]Open the heating module (Top lid) for tare and close the heating module.
[][]Again open the heating module and put the sample on sample pan as mentioned in BMR or test procedure.
[][]Close the heating module and wait for buzzed.
[][]Record the moisture content from the display.
[][]Press the “ON/OFF” key to switch off the instrument.
[][]Wait sufficient time to cool down the instrument in ambient temperature before cleaning.

Calibration Procedure:

Balance calibration

[][]Ensure that the sample pan is in position.
[][]Switch ON the power supply. The display shows “OFF”.
[][]Press the “ON/OFF” key to start the instrument.
[][]The instrument performs a self-test. Wait until the display shown 0.000 g.
[][]Select standard weight of 1g, 5g and 10 g for calibration.
[][]Open the heating chamber and place 1g standard weight on the balance pan at center position.
[][]Repeat previous step no.for 5g. & 10 g.
[][]Record the observations in the calibration report (Annexure–II)

Temperature calibration

[][]Press menu key twice. Display shows “Temperature adj.”
[][]Select “Yes” using scroll keys.
[][]Press “enter” key to start process. Display shows “Remove pan holder”
[][]Open the heating chamber and Remove the sample pan holder from the sample chamber.
[][]Display shows “Insert adjustment kit”. Place the temperature adjustment kit (standard thermometer) in the sample chamber.
[][]Close the heating module to start heating to temperature 100deg. C. The display shows the temperature.
[][]Wait 15 minutes, instrument gives audio signal sound.
[][]Note down the actual temperature on standard thermometer in calibration report (Annexure-II)
[][]Press enter key. The heating module automatically starts calibration at 160deg. C.
[][]Again wait for 15 minutes, instrument gives audio signal sound.

Acceptance Criteria

[][]For balance calibration ± 0.1 % & for temperature calibration ± 30 C.
[][]After completion of calibration switch “OFF” the main supply.
[][]After completion of the calibration activity, affix the duly filled and signed calibration status label on the instrument.
[][]Calibration Frequency
[][]Every six month ± 10 days of due date and after maintenance job.

Cleaning Procedure:

[][]Disconnect the instrument from the power supply before cleaning.
[][]Open the heating module and remove the sampling pan by sampling pan holder.
[][]Clean the sampling pan with soft brush.
[][]Clean exteriors of the instrument by clean dry cloth.
[][]Set the parts of weighing pan carefully and close the heating module

Annexure:

Annexure-I: Log Book Of Moisture Analyzer.
Annexure-II: Calibration Report of Moisture Analyzer.

Calibration of Moisture Analyzer with Operation, and Cleaning Read More »

Semi Automatic Disintegration Tester Operation, Calibration and Cleaning

Semi Automatic Disintegration Tester , Purpose:

Semi Automatic Disintegration Tester , The purpose of this SOP (Standard Operating Procedure) is to describe the operation, calibration and cleaning of Disintegration tester.

Semi Automatic Disintegration Tester , Scope:

This procedure is applicable for Semi Automatic Disintegration tester (Electrolab, Model: ED-2 SAPO) at the Product Development area of XX Pharmaceuticals Limited. This procedure is applicable for Core, Uncoated, Coated tablets and capsules.

Definitions / Abbreviation:

Disintegration Test: The disintegration test is a measure of the time required under a given set of conditions for a group of tablets, Capsule and Other solid dosage forms to disintegrate into particles which will pass through a 10 mesh screen.

Responsibilities:

[][]The roles and responsibility is as follows

Executive, Product Development

[][]To follow the procedure as per SOP.
[][]To maintain the Calibration records.
[][]To ensure cleaning of Disintegration tester maintaining safety rules.

Manager, Quality Assurance

[][]To ensure training and implementation of SOP in department.

Procedure:

Precaution:

[][]Do not switch on the mains if water in the tank is not up to mark.
[][]While placing and removing the basket assemblies do not apply excessive force.
[][]Do not bend the heater while cleaning the water bath.
[][]Do not clean the bath with any strong solvent. Use mild detergents for cleaning.
[][]Lift the machine from the base while lifting or installing.
[][]The external probe should be handled carefully.
[][]To prevent algae propagation in the bath replaces water in the bath at least once in a week.
[][]Remove the external probes when baskets are parked out or removed.
[][]Switch OFF the power supply of the instrument before removing water from the bath.
[][]Do not hold the stirrer while in operation.

Operation: Semi Automatic Disintegration Tester

[][]Ensure the cleanliness of area and the instrument.
[][]Fill the bath with purified water up-to the graduated mark.
[][]Connect the power cord of the instrument to the main power supply.
[][]Check the calibration status of the instrument
[][]Insert the test vessel (jar) in the water bath. Fill the test vessels with purified water / desired media up to 800 ml.
[][]Turn on the power switch provided on the rear side of disintegration tester.
[][]After power on, the instrument will initialize by displaying a power flash screen which will flash twice

DISINTEGRATION
TESTER
ED2-SAPO
VER-1.1

[][]After the power flash screen an idle will be displayed showing the last Mode. Protocol selected for basket A and basket B and the temperature of Jar A, Jar B, and Bath temperature.

Mode: Dual Timer
Proto A: # # Proto B: # #
BATH/ Jar A/ Jar B
# #. /ºC # #. /ºC # #. º

[][]Selection of Registration Mode (For Unknown Disintegration time)
[][]There are two modes: Registration Mode & Dual Timer Mode. Select Registration mode with or keys

Mode: Registration
Proto A: # # Proto B: # #
BATH/ Jar A/ Jar B
# #. /ºC # #. /ºC # #. ºC

[][]Press TEMP key from the front panel a screen will be displayed. Using // key set the temperature to 37.7ºC.
[][]Press TEMP key from the front panel a screen will be displayed. Using // key set the temperature to 37.7ºC.
[][]Press F1 to switch ON the heater. Press TEMP key to register the temperature and come out of the TEMP mode. An idle screen will be displayed. Wait to raise the bath and the jar temperature to desired level.
[][]Assemble the basket-rack.

Operation in Registration Mode

[][]Place six test samples in six tubes. Place the disks if stated in the monographs or in the case of floating products / tablets. Place the disk guides properly to prevent floating of samples.
[][]Press RUN/ HALT key of the respective A or B Jar to run the operation. In Registration mode two separate samples can be tested in two separate jars simultaneously.
[][]Observe the test in each of the tube. If the sample in any of the tube is disintegrated completely just press the key of the respective number. For example if the sample in the number 4 tube of Basket A is disintegrated at first press the number 4 key. Same procedure is followed for all the tubes of each basket.
[][]When Disintegration Time of 6 tablets in one Jar is registered the basket will park out of the media automatically. Press ENTER to return to initial screen.
[][]Observe the disintegration time. To see the time press TIME key. Press F1 to scroll to View Timing mode. Press ENTER. The screen will show the disintegration time of all the six samples. Press F1 key to scroll the screen downward.
[][]To come back into idle screen press ENTER key and press F2 key.

Selection of Dual Timer Mode (For Known Disintegration Time)

[][]When we know the disintegration time of any sample the operation can be done in DUAL TIMER MODE. In this mode there are 10 protocols. An individual sample with its known disintegration time is assigned against each protocol. Select Dual Timer Mode using UP or DOWN keys.
[][]Press TEMP key from the front panel a screen will be displayed. Using BACWARD/UP /DOWN key set the temperature to 37.7ºC.
[][]Press F1 to switch ON the heater. Press TEMP key to register the temperature and come out of the TEMP mode. An idle screen will be displayed. Wait to raise the bath and the jar temperature to desired level.
[][]Press TIME key from the front panel to set the time of a protocol.
[][]When (ARROW) indicates SET TIMER press ENTER button. Using BACWARD/UP /DOWN key adjust the required protocol and time. Press ENTER button to register the time and protocol and come out of the screen.
[][]Press F2 and return to the idle screen.
[][]Assemble the basket-rack.

Operation in Dual Timer Mode

[][]By using BACWARD/UP /DOWN key select different protocols for either jar A or jar B.
[][]Place six test samples in six tubes. Place the disks if stated in the monographs or in the case of floating products / tablets. Place the disk guides properly to prevent floating of samples / disks.
[][]Press RUN/ HALT key of the respective A or B Jar to run the operation.
[][]When the set Time for respective Jar is end up, the basket will park out of the media automatically. Press ENTER to return to initial screen.

Halting / Aborting the Test

[][]Press Run / Halt key to the respective test to be halted.
[][]The respective basket will park out of the media and the display will show the elapse cumulative halt time of the test being halted.

[][]To continue or abort test press Run / Halt key again a screen will be displayed for resuming or aborting the test.
[][]To resume test Press F1.
[][]To abort the test press F2. Press ENTER.

Operation Log Book

[][]Record the information’s in the operational log book- “Operation Log Book of Disintegration Tester (MODEL: ED2-SAPO)”
[][]Calibration of Temperature for Jar A and Jar B
[][]Press TEMP key. Use ▲/◄/▼Key to set the temperature at 37ºC.
[][]Press F1 to switch on the heater. The temperature light will blink.
[][]Press TEMP key to register the temperature and come out of the TEMP mode. An idle screen will display. Wait to raise the temperature at 37.7ºC in the both jars.
[][]When the screen displays a fixed temperature for Jar A and Jar B from temperature sensor, measure the temperature of both Jars by a calibrated thermometer.
[][]Keep the records of calibration as per Annexure-I.
[][]Acceptance Range: ± 2ºC of the display temperature.
[][]Calibration of Timer for Basket-A
[][]Select the Dual Timer mode by pressing ▼/▲key.
[][]Use ◄ key to select Proto A.[START OF SECTION ONE]
[][]Press the option menu.
[][]Press F1 (scroll) key to select set protocol. Press Enter key.
[][]Press ▼/▲ key to set a specific protocol no. (e.g. 01, 02, 03 …) under Proto A.
[][]Press F1 (scroll) key to enter the Timer option.
[][]Set the timer (5 minutes) by using ▲/◄/▼key.
[][]Press F2 key twice to return to the idle screen.
[][]Press the Run key in the front panel and start the calibrated stop watch to compare the time.

[][]After completion of the specified time (5 minutes) ‘Test is over’ is appeared on the screen with beeping sound.
[][]Press Enter key to return to the idle screen.
[][]Keep the records of calibration as per Annexure-I.
[][]Acceptance Range: 5 minutes.[END OF SECTION ONE]

Calibration of Timer for Basket-B

[][]Use ◄ key to select Proto B.
[][]Follow previous steps [START OF SECTION ONE] TO [END OF SECTION ONE]
[][]Calibration of Stroke/min. for Basket-A
[][]Check the jar temperature. If temperature is not in the desired level, wait for raising the temperature (37.7°C) in the jar.
[][]Follow previous steps
[][]Press the RUN key and start the stop watch to count the no. of strokes per minute.
[][]Press the Halt key twice and then Test A is displayed.
[][]Press F2 to abort. The screen will display ‘Test is over’.
[][]Press Enter key to return to the idle screen.
[][]Keep the records of calibration as per Annexure-I.
[][]Acceptance Range: 29 to 32 Stroke/min.
[][]Calibration of Stroke/min. for Basket-B
[][]Follow previous steps(In case of Proto B, Use ◄ key to select Proto B).
[][]Calibration of Traveling Distance for Basket-A
[][]Follow previous steps
[][]Press Run key to travel the Basket A in upward and downward stroke.

[][]When the basket is in the downward stroke position, Press the power switch (Rear side of the instrument) to off quickly.
[][]Now Mark the position (Xa) of the basket holder by a pencil.
[][]Press the power switch on.
[][]Press the TEMP key.
[][]Press F1 to on the heater. The temperature light will blink.
[][]Press TEMP key to return to the idle screen position.
[][]Wait for the desired setting temperature (37°C). When it reaches to the desired level, Press the Run key. The basket will travel upward and downward stroke.
[][]When it comes to the upward stroke position, Press the power switch (Rear side of the instrument) to off quickly.
[][]Mark the position (Ya) of the basket holder by a pencil.
[][]Now measure the traveling distance between Xa and Ya by a standard certified scale.

Xa – Ya= ## mm.
[][]Keep the records of calibration as per Annexure-I.
[][]Acceptance Range: 55 ± 2 mm.
[][]Calibration of Traveling Distance for Basket-B
[][]Press the power switch (Rear side of the instrument) to on.
[][]Press the TEMP key. Use ▲/◄/▼key to set the temperature at 37ºC.
[][]Press F1 to switch on the heater. The temperature light will blink.
[][]Press TEMP key to return to the idle screen position.
[][]Wait for the desired setting temperature (37.7°C). When it reaches to the desired level Press the Option Key.
[][]Follow steps  (In case of Proto B, Use ◄ key to select Proto B).
[][]Follow steps

Calibration of Basket A to Beaker Bottom Height

[][]Unscrew Basket A from the bottom and remove the basket bottom plate.
[][]Remove one tube (with Blue or Brown indication) and engage the basket to the basket holder.
[][]Insert the measuring scale (6 inch) into the disc from where the tubing has been removed. Care should be taken that the scale touches the bottom of the beaker.
[][]Press the power switch (Rear side of the instrument) to on.
[][]Press the TEMP key.
[][]Press F1 to on the heater. The temperature light will blink
[][]Press TEMP key to return to the idle screen position.
[][]Wait for the desired setting temperature (37°C). When it reaches to the desired level, Follow steps
[][]Press the Run key to travel the Basket A in upward and downward stroke.
[][]When the basket is in the downward stroke position, Press the power switch (Rear side of the instrument) to off quickly.
[][]Measure the Basket A to bottom height during the downward stroke by certified measuring scale.
[][]Keep the records of calibration as per Annexure-I.
[][]Acceptance Range: 25 ± 2 mm.

Calibration of Basket B to Beaker Bottom Height

[][]Follow steps

[][]Set the parts of the instrument and clean the instrument.
[][]Calibration Frequency: 3 months ± 10 days.

Cleaning

[][]After completion of a test clean the basket-rack assembly with potable water and if required with a mild detergent.
[][]Whenever required use a suitable brush to remove any residue of the previous sample from the mesh screen.
[][]Use potable water to clean the jar and bath.
[][]Finally rinse the basket rack assembly, jar & bath with purified water and dry in air.
[][]Cleaning frequency of basket rack assembly & jar : After every test
[][]Cleaning frequency of water bath: Once in a week.
Note: In between when water become dirty change water
[][]After cleaning of the disintegration test apparatus water bath, record it as per Annexure-III

Annexure: Semi Automatic Disintegration Tester

Annexure-I: Operation log book of Disintegration Tester(Model: ED2-SAPO)
Annexure –II: Calibration report of disintegration tester.
Annexure-III: Cleaning record for Disintegration water bath.

Semi Automatic Disintegration Tester Operation, Calibration and Cleaning Read More »

Electric Stirrer Operation, Cleaning and Maintenance Procedure

Electric Stirrer , Purpose :

Electric Stirrer,  The purpose of this SOP is to describe the Operation, cleaning and maintenance procedure of Electric Stirrer (Model: ES) in order to comply with cGMP standard.

Electric Stirrer , Scope :

The scope of the procedure is applicable to the Electric Stirrer (Model: ES) at the Product Development area of XX Pharmaceuticals Pvt. Limited.

Definitions / Abbreviation:

[][]None

Responsibilities:

The roles and responsibility is as follows:

Operator/Supervisor Product Development

[][]Operation and cleaning of the Electric Stirrer (Model: ES)
[][]Maintaining operation and cleaning log book

Executive/ Sr. Executive Product Development

[][]Checking and ensuring that the operation and cleaning is performed according to the SOP.
[][]Checking the log book.
[][]Preparation and timely review of the SOP.

Manager Engineering

[][]Preparation of maintenance schedule and maintenance of the machine.

Manager, Quality Assurance

[][]Ensure that the SOP reflects actual operation, cleaning and maintenance procedure.
[][]Approve the SOP against XX Pharmaceuticals Ltd. Master documents and current regulatory requirements.
[][]Implementation of the SOP.

Procedure:

Machine Assembling

[][]Attach required sieve in the sieve holding clamp of the machine.
[][]Attach bolts and tighten the knobs to ensure that the sieve is properly installed in the machine.
[][]Rotate the shaft clamp to loosen the main shaft.
[][]Push the shaft downward to lower the main shaft and pull the shaft upward to rise the main shaft holding the propeller and sieve.
[][]Rotor the shaft clamp anticlockwise to tighten the main shaft.
[][]Ensure that the main shaft is properly tightened before running the machine. Donot run the machine if the shaft is not properly tightened.
[][]Check for all the bolts to be tightened properly.

Machine Operation

[][]Connect the main electric supply with the socket.
[][]Three lights (Red, Green and Yellow) illuminates to show the proper functioning of the three phase connection of the machine.
[][]Adjust the secondary propeller according to the need of the liquid to be stirred. If secondary propeller is not required adjust it higher than the liquid lavel.
[][]Make sure that both propeller is submerged in the liquid to be stirred.
[][]Push the Forward button to rotate the propeller clockwise and push the backward button to rotate the propeller anticlockwise.
[][]To stop the machine instantly push the stop button.
[][]To switch from forward rotation to backward rotation first push the stop button and when the machine is stop then push the backward button.
[][]Do not switch directly from one rotational direction to another direction.
[][]Display will show the RPM of the machine, do not change any parameter in the inverter. Changing parameters in the inverter will stop the machine immediately.
[][]To change or adjust the machine speed use the speed controlling regulator. Clockwise rotation will increase the RPM and anticlockwise rotation will decrease the RPM.
[][]When the display shows 60 in the screen the machine tends to rotate in 2800 RPM. Do not run the machine more than 1400 RPM that is 30 in the screen.
[][]To stop the machine push the stop button and the machine will stop automatically.

Machine Dismantling

[][]Disconnect the machine from the main electric supply.
[][]Rise the main shaft from the liquid. Remove the remaining liquid(if any) from the sieve holding clamp and remove the solution preparation mug.
[][]Loosen the sieve holding bolts, remove the sieve and take in a poly bag
[][]Loosen the primary propeller with the help of a range, and remove from the machine.

Machine Cleaning

[][]If the machine doesn’t used within 15 days after cleaning, then the machine should be cleaned on the 15th day.
[][]Clean the sieve holding clamp, secondary propeller and the main shaft of the machine with lint free cloth wiped in potable water.
[][]Repeat the procedure twice to remove all solution from the machine.
[][]Clean the secondary propeller and the clamp with brush to remove any part of the solution adhering to the machine.
[][]Rub gently with lint free cloth to remove any solution adhering to the machine.
[][]Wipe the cloth in hot water and rub the machine, Clean all the machine parts with hot water, then finally rinse with purified water.
[][]Clean the motor covering , Main shaft and the base of the machine with potable water, Rub the parts with lint free cloths wipe din potable water than rinse with purified water.
[][]Wipe the machine with dried lint free cloth to remove water from the machine. Use compressed water to remove water as necessary.
[][]Submerge the sieve and the primary propeller in potable water for 10 minutes.
[][]Clean the parts with tap water to remove any part of the solution.
[][]Use brush and lint free cloth to properly clean the parts.
[][]Submerge the parts in hot water, Clean the parts with hot water finally rinse with purified water.
[][]Rub the machine parts with lint free cloths and compressed air to remove water.
[][]Take the dried sieve and the sieve holding bolts in a poly bag attach a cleaned label and store in the cabinet.
[][]Install the propeller in the main shaft. Attach a Cleaned label in the machine.

Annexure:

Annexure – I: Operation and cleaning log book.

Electric Stirrer Operation, Cleaning and Maintenance Procedure Read More »

Hand Capsule Filling Machine Operation, Cleaning and Maintenance Procedure

Hand Capsule Filling Machine, Purpose :

Hand Capsule Filling Machine, The purpose of this SOP is to define the operation, cleaning and maintenance procedure of manual capsule filling machine. Model: PCF 300

Hand Capsule Filling Machine, Scope :

This SOP is applicable for operation, cleaning and maintenance procedure of manual capsule filling machine in product development laboratory of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]None

Responsibilities:

[][]The roles and responsibility is as follows:

Operator/Supervisor Product Development

[][]Operation and cleaning of the Manual Capsule Filling Machine
[][]Maintaining operation and cleaning log book

Executive/ Sr. Executive Product Development

[][]Checking and ensuring that the operation and cleaning is performed according to the SOP.
[][]Checking the log book.
[][]Preparation and timely review of the SOP.

Assistant Manager Engineering

[][]Preparation of maintenance schedule and maintenance of the machine.

Manager, Quality Assurance

[][]Ensure that the SOP reflects actual operation, cleaning and maintenance procedure.
[][]Approve the SOP against XX Pharmaceuticals Ltd. master documents and current regulatory requirements.
[][]Implementation of the SOP.

Procedure:

Machine Assembling

[][]Before operation assemble the machine change parts that are necessary for certain type of operation.
[][]Attach the required type of change parts for the expected operation in the machine

Machine Setup

[][]Tag the filling machine with a Machine Label before use.
[][]Arrange empty capsule shell on the loading tray.
[][]Place the loading tray with empty capsule on the machine.
[][]Grip cam lever and pull towards the front.
[][]Push the inner slide knob.
[][]Depress the lifting plate lever.
[][]Lift the loading tray up.
[][]Separate the capsule bottom half (Bodies) from the cap.
[][]Check the entire cap and bodies are separated.
[][]Keep the loading tray with separated cap on the table carefully.
[][]Release the lever to drop down the bodies to sit in level with the top section.
[][]Place the filling tray on the machine. Ensuring the tray is properly located in holes provided in the top section.
[][]Pour the pre-weighed Powder /Pellet

Machine Operation for powders

[][]Spread the powder using Teflon dispenser over the top section to fill the body uniformly.
[][]If any powder remains on the tray, take aside the excess powder with the powder dispenser on to the platform provided on the right of the tray. Lower the pin plate assembly and lock it in position using pin plate locking lever to compact the powder.
[][]Unlock the lever, open the pin plate and spread the remaining powder (if necessary follow further step: 10.4.1. and 10.4.2.).
[][]Remove the filling tray. Place the loading tray with separated cap on the top section.
[][]Pull out the inner slide knob.
[][]Lower the pressure plate and lock in position with locking lever.
[][]Move the lifting plate lever downward for proper locking of the capsule.
[][]Unlock the pressure plate and take it back to its original position.
[][]Push the inner slide knob.
[][]Depress the lifting plate lever.
[][]Lift the loading tray up with locked capsule.

[][]Empty the locked capsule into a suitable container
[][]Remove the product container. Use plastic bag to wrap under the discharge chute. Clean the sieve to remove the materials that cannot pass though the sieve (If product is very sticky, the sieve might require to be removed for a thorough cleaning with brush and cleaning agent).
[][]Clean the machine after completing the operation of the day or before changing to process other products.

Machine operation for pellets.

[][]Spread the pellets using Nylon brush over the top section to fill the body uniformly.
[][]Remove the filling tray. Place the loading tray with separated cap on the top section.
[][]Pull out the inner slide knob.
[][]Lower the pressure plate and lock in position with locking lever.
[][]Move the lifting plate lever downward for proper locking of the capsule.
[][]Unlock the pressure plate and take it back to its original position.
[][]Push the inner slide knob.
[][]Depress the lifting plate lever.
[][]Lift the loading tray up with locked capsule.
[][]Empty the locked capsule into a suitable container
[][]Clean the machine after completing the operation of the day or before changing to process other products.

Machine Dismantling

[][]Remove the powder tray.
[][]Open the cam lever.
[][]Remove the eccentric pin.
[][]Remove the top section by loosening four screws.
[][]Pull out sliding sheet from the top section.

Machine Cleaning

[][]If the machine doesn’t used within 15 days after cleaning, then the machine should be cleaned on the 15th day.
[][]Wash the powder tray, cam lever, top section with sliding sheet, nylon brush, powder dispenser and the main body (lifting plate assembly, pin plate assembly and pressure plate assembly) with potable water.
[][]Wipe with damp markin cloth by rubbing to remove any adhering materials
[][]Wash with potable water again
[][]Wash with hot water using damp cloth to remove any insoluble material
[][]Wash with hot water and then with purified water.
[][]Wipe with clean, dry markin cloth to remove any water
[][]Dry with compressed air where necessary
[][]Wrap with poly bag, attach “CLEANED” label and store in the accessories cabinet.
[][]Clean eccentric pin with cotton cloth and lubricate it.
[][]Push the sliding sheet into the top section.
[][]Mount the top section onto the main body by four screws.
[][]Assemble the eccentric pin and cam lever.
[][]Keep the loading tray and powder tray with attached “CLEAN” label in accessories cabinet.
[][]Attach “CLEANED” label in the machine in store in the Table.

Annexure: Hand Capsule Filling Machine

Annexure – I: Operation and cleaning log book.

Hand Capsule Filling Machine Operation, Cleaning and Maintenance Procedure Read More »

Multi mill operation and cleaning procedure

Multi mill , Purpose :

Multi mill , The purpose of this SOP is to describe the Operation and cleaning procedure of Multi Mill (Model: GMP) in order to comply with cGMP standard.

Multi mill , Scope :

The scope of the procedure is applicable to the Multi Mill (Model: GMP) at the Product Development area of  XX Pharmaceuticals Pvt. Limited.

Definitions / Abbreviation:

[][]None

Responsibilities:

[][]The roles and responsibility is as follows:

Operator/Supervisor Product Development

[][]Operation and cleaning of the Multi Mill (Model: GMP)
[][]Maintaining operation and cleaning log book

Officer/ Sr. Officer Product Development

[][]Checking and ensuring that the operation and cleaning is performed according to the SOP.
[][]Checking the log book.
[][]Preparation and timely review of the SOP.

Assistant Manager Engineering

[][]Preparation of maintenance schedule and maintenance of the machine.

Manager, Quality Assurance

[][]Ensure that the SOP reflects actual operation, cleaning and maintenance procedure.
[][]Approve the SOP against XX Pharmaceuticals Ltd. Master documents and current regulatory requirements.
[][]Implementation of the SOP.

Procedure:

Machine Assembling

[][]Loosen the knobs of the Discharge covering. Anticlockwise rotation of the knobs will loosen and clockwise rotation will tighten the discharge unit
[][]Remove the discharging unit from the machine. Rotate the covering slightly at any direction and pull downward to remove smoothly.
[][]Rotate the screws of the Mesh holding plate anticlockwise direction to loosen the plate. Rotate the plate anticlockwise and remove from the machine.
[][]Check for the proper tightening of the knife and knife holding shaft.
[][]Set desired mesh on the mesh slot, push upward to set the mesh properly.
[][]Install the mesh holding plate, tighten the mesh holding plate properly. Do not run the machine without properly tightening the knobs.
[][]Install the Discharge unit in the, tighten all the knobs of the discharge unit to properly set the machine.
[][]Check for the proper positioning, functioning and installation of the hopper, feed controlling plate and the hopper covering.

Machine Operation

[][]Connect the main electric supply with the socket.
[][]Three lights (Red, Green and Yellow) illuminates to show the proper functioning of the three phase connection of the machine.
[][]Remove the covering of the hopper to charge the materials in the hoper. Keep the feed control plate fully closed while charging the materials.
[][]Pull the feed control plate outward to control the material entry in the milling zone.
[][]Install the hoper covering, do not run the machine without the covering installed properly.
[][]Push the Forward button to rotate the blades clockwise and push the backward button to rotate the blades anticlockwise.
[][]To stop the machine instantly push the stop button.
[][]To switch from forward rotation to backward rotation first push the stop button and when the machine is stop then push the backward button.
[][]Do not switch directly from one rotational direction to another direction.
[][]Display will show the RPM of the machine, do not change any parameter in the inverter. Changing parameters in the inverter will stop the machine immediately.
[][]To change or adjust the machine speed use the speed controlling regulator. Clockwise rotation will increase the RPM and anticlockwise rotation will decrease the RPM.
[][]When the display shows 28 in the screen the machine tends to rotate in 1400 RPM. Machine can be run in more speed than that, but don’t run the machine in speed more than 28 in display.
[][]To stop the machine instantly push the stop button and the machine will stop automatically.

Machine Dismantling

[][]Disconnect the machine from the main electric supply.
[][]Remove the Hopper cover and the feed control plate from the machine.
[][]Loosen the screws in the hopper than remove the hopper from the machine.
[][]Rotate the knobs in the discharge unit, rotate the discharge unit than pull downward to remove the discharge unit from the machine.
[][]Rotate the knobs in the mesh holding tray anticlockwise to loosen the screws. Rotate the knobs anticlockwise and remove the tray.
[][]Pull the mesh downward to separate the mesh from the machine.
[][]Use a socket set to remove the knife shaft from the machine.
[][]Loosen the screw on the downward of the machine.
[][]Pull the shaft backward. The shaft with the knives will come out.
[][]Remove the pin holding cap on the top of the shaft.
[][]Pull out the pins from the shaft.
[][]Remove the knives and the scrapers by pulling them in outer direction.

Machine Cleaning

[][]After removal and dismantling of all change parts take the change parts in the cleaning bay.
[][]Use vacuum cleaner to remove any remaining powder from the machine body.
[][]Wash the machine body, shaft, basement and motor holding portion wish wet lint free cloth.
[][]Wash the machine with hot water if necessary, then finally rinse the machine with wet cloth submersed in purified water.
[][]Dry the machine with dried lint free cloth. Use compressed air if necessary to remove water from the critical places.
[][]Clean the wire with wet cloth and dry using lint free cloths.
[][]Clean all the change parts with potable water, use cloth to rub well to remove any portion of powder from the machine.
[][]Use hot water to clean all the machine parts, use nylon brush if necessary to remove any remaining quantity of powder dust
[][]Use nylon brush to clean the knives and brush through the knife shaft to remove any portion of powder.
[][]Run the whole procedure twice for knife and knife holding shaft.
[][]Rinse the parts with purified water. Dry all the change parts with lint free dried cloth, Use compressed air to remove water from the critical areas.
[][]Use compressed air to remove the water from the knife holding zone in the shaft.
[][]Attach the knives with the shaft and lock with the pin
[][]Attach pin holding top to keep the pin in position.
[][]Fix the knife shaft in the machine and tighten with the socket set, check for the proper fixing of the machine.
[][]Attach the sieve holding plate and the discharge unit with the machine
[][]Install the hopper, feed control plate and the hopper covering in the machine. Attach a CLEANED label in the machine.
[][]Clean the sieve with potable water, use dump cloth to properly remove powder.
[][]Use hot water to clean the sieve properly, use nylon brush to remove any quantity of powder.
[][]Rinse the sieve with purified water, dry the sieve with dried lint free cloth, use compressed water first to remove the water from the sieve then use lint free cloth to dry the sieve.
[][]Take the sieve in a poly bag, attach a cleaned label in the bag and store in the cabinet for machine change parts.

Annexure:

Annexure – I: Operation and cleaning log book.

Multi mill operation and cleaning procedure Read More »

Coating Machine Operation and Cleaning Procedure

Coating Machine , Purpose:

Coating Machine , The purpose of this SOP is to define the operation and cleaning procedure of Coating machine.

Coating Machine , Scope:

This SOP is applicable for operation and cleaning procedure of Coating machine in product development of General Block at XX Pharmaceuticals Limited.

Definition / Abbreviation:

None

Responsibilities:

The roles and responsibility are as follows:

Operator/Supervisor Product Development

[][]Operation and cleaning of the Coating machine
[][]Maintaining operation and cleaning log book

Executive/ Senior Executive, Product Development

[][]Checking and ensuring that the operation and cleaning is performed according to the SOP.
[][]Checking the log book.
[][]Preparation and timely review of the SOP.

Manager, Quality Assurance

[][]Ensure that the SOP reflects actual operation and cleaning procedure.
[][]Approve the SOP against XX Pharmaceuticals Limited master documents and current regulatory requirements.
[][]Implementation of the SOP.

Procedure

[][]Machine Assembling
[][]Before operation assemble the machine accessories that are necessary for operation.
[][]Place the spray gun at the holding arm. Then, enter the spray gun holding arm into the coating pan.
[][]Connect the peristaltic pump with the spray gun.
[][]Test whether coating pan rotates smoothly without any abnormal noise after activation. Check that rotation direction is correct.

Machine Operation

[][]Connect the power cable to the socket for power supply.
[][]Switch on the Machine.
[][]Unlock and open the inlet port cover of the machine.
[][]Load tablets into the coating pan. Total tablet load should not exceed the maximum working load and should not be less than the minimum working load.
[][]Securely close the coating pan chamber cover and clamp.
[][]Outlet blower ‘‘ON/OFF” by pressing the push button.
[][]Pan motor ‘‘ON/OFF’ by pressing the push button.
[][]Inlet blower” ON/OFF” by pressing the push button.
[][]Warm up the tablets without spraying on the tablet bed.
[][]Start spraying phase by pressing the pump start button in manual mode or Spray key in Auto mode. Adjust dosing volume by changing the rpm of the peristaltic pump.
[][]After spraying, stop the Spray by pressing Pump ON/OFF button. Dry the tablets until required
[][]Unload the tablets from the coating pan when desired tablet temperature is attained.

Machine Cleaning

[][]If the machine doesn’t used within 15 days after cleaning, then the machine should be cleaned on the 15th day.
[][]Switch off outlet damper, blower, pan motor, inlet blower.
[][]Open all safety doors.
[][]Dismantle spray system.
[][]Switch on the peristaltic pump by pressing “Switch on button”.
[][]Wash the inside of tube by spraying with hot water followed by purified water.
[][]Again wash the tube with purified water.
[][]The compressed air through tube to dry inside of tube.
[][]Clean the Spray gun nozzle with hot water and soft brush.
[][]Now discharge the water with dissolved materials.
[][]Now hot water is applied inside the chamber to remove materials fixed hardly on the chamber surface.
[][]Wash the machine with wet markin cloth.
[][]Re-wash the machine with purified water as required. Finally rinse with purified water.
[][]Clean inlet ports, discharge port, mixing chamber and external surface with damp cloths.
[][]Wipe the water droplets with cloth, and dry the machine with compressed air.
[][]Fix ‘CLEANED’ label on the machine.
[][]Keep the record of machine operation and cleaning according to the Annexure – I of this SOP.

Annexure:

Annexure – I: Operation and cleaning log sheet of Coating machine, Model: FC 15”-E

Coating Machine Operation and Cleaning Procedure Read More »

Compression machine operation and cleaning procedure

Compression machine, Purpose :

Compression machine, The purpose of this SOP is to describe the Operation and cleaning procedure of CAMBERT Tablet Compression Machine (Model: KMP DB8) in order to comply with cGMP standard.

Compression machine, Scope :

The scope of the procedure is applicable to the CAMBERT Tablet Compression Machine (Model: KMP DB8) at the Product Development area of XX Pharmaceuticals Pvt. Limited.

Definitions / Abbreviation:

[][]None

Responsibilities:

[][]The roles and responsibility is as follows:

Operator/Supervisor Product Development

[][]Operation and cleaning of the CAMBERT Tablet Compression Machine (Model: KMP DB8)
[][]Maintaining operation and cleaning log book

Executive/ Sr. Executive Product Development

[][]Checking and ensuring that the operation and cleaning is performed according to the SOP.
[][]Checking the log book.
[][]Preparation and timely review of the SOP.

General Manager, Engineering

[][]Preparation of maintenance schedule and maintenance of the machine.

Manager, Quality Assurance

[][]Ensure that the SOP reflects actual operation, cleaning and maintenance procedure.
[][]Approve the SOP against XX Pharmaceuticals Ltd. Master documents and current regulatory requirements.
[][]Implementation of the SOP.

Procedure: Compression machine

[][]Machine Assembling
[][]Remove the site glass of all sides
[][]Setting of Die
[][]Ensure that the die pockets are cleaned.
[][]Smear the die with food grade oil and place n the die pocket of the die table.
[][]Press the die down with finger to locate accurately the die in the die pocket.
[][]Once the die is located enter the die bar through the upper punch guide hole and allow to drop from a height of 70 – 80 mm approximately.
[][]The die will enter in the pocket apply additional force through die bar until the die is fully down on the die pocket.
[][]In order to set the shaped die enter the upper punch first and align the die cavity with the upper punch and gently push the die with the punch to enter in the die pocket, then apply additional force to fully down the die in the die pocket.
[][]Ensure that the top face of the die is perfectly flash with the die table.
[][]Tighten the die screw with the allen key. Ensure that the die is flash with the die table after tightening. Do not run the machine if die screw is not properly tightened.
[][]Use four blank dies ( four for B tooling and four for D tooling separately) in respective die cavity and install in the same procedure.

Setting of lower punch

[][]Remove the R.H. lower panel to access punch loading plug
[][]Remove the punch loading plug from the middle plate by just pushing it from bottom.
[][]Rotate the turret slowly with the help of hand wheel and align punch guide hole with the punch loading plug cavity.
[][]Insert the punch in to guide hole. Push the punch to its highest position and ensures it drops freely under its own weight. Tighten the punch holding plug with a screw driver.
[][]Carefully rotate the turret by means of the hand wheel until the punch is clear of the loading port.
[][]Set all the lower punch in the same way.
[][]Install the Punch loading plug in the middle plate.

Setting of upper punch

[][]Ensure that the punch guide holes and punches are clean.
[][]Place the punches in the punch holes and check that each punch is free to move in its guide and capable of dropping in to the cam track by its own weight.
[][]Rotate the turret at least one full turn by fly wheel to recheck to ensure that the upper punches enter the die bores without tipping and they run freely throughout the cam system.
[][]In order to set shaped punches (other than round) remove the punch take out plate for upper punch. Then place the punch in the punch holes and observe that the punch is fitted with the die without any friction, than rotate the fly wheel until the upper punch is removed to the punch head fitted position.
[][]Set all the punches in the same manner, then refit the punch take out plate in position.
[][]Rotate the machine manually through fly wheel to ensure that die punch are set correctly and the machine can be run without any friction.
[][]Install the force feeder in front of the machine. Ensure that no part is in touch with the main turret. Tighten the bolts of force feeder. Rotate the machine manually through fly wheel to ensure machine rotates without hindrance.
[][]Install the tablet ejection chute at the right side of the machine. Ensure that no part of the machine is in contact with the turret. Tighten the screw so that the ejection chute.
[][]Install the hopper above the force feeder.
[][]Connect the coupling with the feeder drive, shaft. Lock the coupling.
[][]Check that all nut bolts are tightened correctly.
[][]Install the R.H lower panel and the site glass. The machine is ready to use.

Machine Operation

[][]Rotate the machine through fly wheel and check that there is no abnormal sound in the machine
[][]Connect the main electric supply with the socket.
[][]Turn the machine on off switch to right direction, main drive and feeder drive button light will lights will illuminate to indicate machine is supplied with proper electric supply.
[][]Remove the R.H lower panel and keep the weight adjustment and thickness adjustment wheel at lower position, install the R.H. lower panel.
[][]Keep the speed adjustment knob at low and press the main drive button to ensure that the machine runs without any abnormal noise or hindrance.
[][]Press the main drive off switch, turret will stop.
[][]Remove the lid of the hoper and pour powder in the hoper, Push the feeder drive button feeder will start, wait until powder is transferred to the filling area.
[][]Fix the upper punch penetration wheel at its desired position (from 2 to 6 mm) depending on the punch and product type. Do not change the position of the wheel during operation.
[][]Fix the precompression wheel at its desired position (from 2 to 4), do not change the position of pre compression wheel during operation.
[][]Push the main drive button, turret will start, ensure that the powder are filled accurately in the die cavity.
[][]Rotate the thickness adjustment wheel clockwise until the powders take the shape of tablet.
[][]Adjust the weight of the tablet by rotating the filling depth adjustment wheel clockwise. Clockwise rotation will decrease the tablet weight and anticlockwise rotation will decrease the weight of the tablet.
[][]After desired tablet weight is achieved, adjust the thickness of the tablet. Clockwise rotation of thickness adjustment wheel will decrease the thickness and anticlockwise rotation will increase the thickness.
[][]Tablet hardness will also be adjusted by the thickness adjustment wheel. Clockwise rotation of the wheel will increase the hardness and anticlockwise rotation will decrease the hardness.
[][]Once tablet of desired quality is achieved set the turret speed. Turret speed can be adjusted by the speed adjustment knob. Clockwise rotation of the knob will increase the speed and anticlockwise rotation will decrease the speed.
[][]With any change in the turret speed, feeder speed is also needed to adjust. Clockwise rotation of the feeder speed adjustment knob will increase and anticlockwise rotation will decrease the feeder speed.
[][]Check the tableting parameters (Weight, Hardness and thickness) while turret speed is increased or decreased. Adjust the weight and thickness if necessary.
[][]Rotate the tablet counting key at right side. Counter will start counting the tablets. To watch counting in number of tablet in display place the counter knob at number of tablet position and to watch the turret speed place the counter knob at RPM position.
[][]To stop the turret, press turret off button and to stop the feeder drive, press feeder drive stop button.
[][]To stop the machine instantly, rotate the main switch at left position, machine will stop.

Machine Dismantling

[][]Remove the site glass in front side of the machine.
[][]Remove to material lock from the force feeder, place a poly bag and on the force feeder, excess materials will be flown in to the poly bag.
[][]Switch off the machine, Remove the main power supply form the socket.
[][]Adjust the filling depth wheel and thickness adjustment wheel at the lowermost position
[][]Loosen the ejection chute holding screw and remove the ejection chute

Remove the hoper.

[][]Unlock the feeder drive shaft from the coupling and keep aside. Loosen the force feeder holding screw then remove the force feeder.
[][]Remove the upper punches
[][]Remove the lower RH panel and punch loading plug.
[][]Rotate the machine manually and align the lower punch with the punch loading cavity.
[][]Loosen the punch holding plugs. Punch will automatically come out of the cavity, if required press gently downward and collect the punch.
[][]Remove all the lower punch in the same manner.
[][]Loosen all the die locking screw up to maximum limit.
[][]Enter the die bar from the punch loading cavity. Align the die with the cavity then gently apply pressure upward to remove the die. If necessary apply force through tamping. Die will come out of the die cavity. Remove all the die in the same manner.
[][]Install the lower RH Panel

Machine Cleaning

[][]If the machine doesn’t used within 15 days after cleaning, then the machine should be cleaned on the 15th day.
[][]Remove dusts from the machine with a vacuum cleaner. Collect dust from the turret, punch holding cam, operation panel and machine body.
[][]Clean all the machine parts with dry lint free cloth. Clean the die cavity & die holding plug with a flush brush. Use brush to clean any material sticking in the machine parts, screw and knobs.
[][]Use potable water to clean the turret, machine body, cam, punch holding cavity operation panel, die cavity and die holding screw.
[][]Use hot water to clean all the above mentioned body parts & finally rinse with purified water.
[][]Clean and sob with lint free cloth all the parts to dry any water in the machine body.
[][]Attach RH panel and site glass and stick a cleaned label in the machine.

Cleaning of die and punches

[][]Clean the die and punch with lint free cloth to remove any particle in the die and punch.
[][]Flash the die hole with flash brush and use brush to clean any particle sticking with the die and punch.
[][]Clean the die and punch with potable water, use brush if necessary.
[][]Clean the die and punch with hot water and finally rinse with purified water.
[][]Sob any water present in the die and punch with lint free cloth.
Smear the die and punches with food grade oil and store in the die punch cabinet.

Cleaning of force feeder

[][]Remove the screws of force feeder and open the cover of feeder housing
[][]Remove the paddle and paddle key from the machine and collect dust particle from the feeder housing with vacuum cleaner.

[][]Clean all the parts with lint free cloth.
[][]Clean all the parts with potable water, use Teflon brush if necessary
[][]Clean all machine parts with hot water and then rinse with purified water.
[][]Remove any water particle from the parts with lint free cloth.
[][]Assemble the paddle and cover in the feeder housing and take in a poly bag. Attach a cleaned label in the bag and store in the machine parts cabinet

Cleaning of hopper and ejection chute

[][]Clean all the powder with lint free cloth
[][]Use potable water to clean the hopper and the ejection chute, use Teflon brush where necessary.
[][]Clean the machine with hot water, then rinse with purified water.
[][]Clean and sob out any water remaining in the machine parts with lint free cloth.
[][]Wrap the change parts with poly bag, attach cleaned label in the poly bag and store in the machine parts cabinet.

Annexure: Compression machine

Annexure – I: Operation and cleaning log book.

Compression machine operation and cleaning procedure Read More »

Container blender operation and cleaning procedure

Container blender, Purpose:

Container blender, The purpose of this SOP is to define the operation and cleaning procedure of container blender.

Container blender, Scope:

This SOP is applicable for operation and cleaning procedure of container blender in product development of XX Pharmaceuticals Limited.

Definition / Abbreviation:

[][]None

Responsibilities:

[][]The roles and responsibility are as follows:

Operator/Supervisor Product Development

[][]Operation and cleaning of the container blender
[][]Maintaining operation and cleaning log book

Executive/ Senior Executive, Product Development

[][]Checking and ensuring that the operation and cleaning is performed according to the SOP.
[][]Checking the log book.
[][]Preparation and timely review of the SOP.

Manager, Quality Assurance

[][]Ensure that the SOP reflects actual operation and cleaning procedure.
[][]Approve the SOP against XX Pharmaceuticals Limited master documents and current regulatory requirements.
[][]Implementation of the SOP.

Procedure:

Machine Assembling

[][]Before operation assemble the machine accessories that are necessary for operation.
[][]Place the container at the holding arm of the blender. Then, secure it with the holding arm.
[][]Securely close and lock of inlet ports and outlet port in place.
[][]Test whether container rotates smoothly without any abnormal noise after activation. Check that rotation direction is correct according to the arrow sign.

Machine Operation

[][]Connect the power cable to the socket for power supply.
[][]Turn the machine ON/OFF switch (main switch at the right down corner of the machine) to ON. Control panel light will illuminate and the machine is ON.
[][]Unclamp and open the inlet port cover.
[][]Load raw materials into the chamber. Total material load should not exceed the maximum working volume and the minimum working volume.
[][]Securely close the mixing chamber cover and clamp.
[][]Release the EMERGENCY SWITCH, MIXER STOP SWITCH will light up, indicating that the electricity is supplied to the control system and the machine is ready to perform the process.
[][]Set Timer process according to the timer required for the mixing process.
[][]Activate the mixer.
[][]Observe carefully, there is no abnormal noise generated by the blender.
[][]Ensure that there is no leakage in inlet valve and outlet valve during the mixing.
[][]Check that the timer counts down the time. Once the set time is reaches, the mixer will stop operation accordingly.
[][]Place a collection bin under the outlet port. Plastic or clothing bag might be wrap between outlet port and other collection bin to prevent product dispersion into the room.
[][]Open the outlet valve to discharge the product into a collection bin. Open the inlet port to check whether there is any remaining product inside the container.
[][]Shut the outlet port after all product removed.
[][]In case of manual operation set TIMER OFF/ON selector to OFF. And activate the blender.
[][]Push EMERGENCY SWITCH button to discontinue the electrical supply to the system.
[][]Clean the machine as per above cleaning procedure.
[][]Turn the machine ON/OFF button to OFF. The machine light will be OFF.

Machine Cleaning

[][]If the machine doesn’t used within 15 days after cleaning, then the machine should be cleaned on the 15th day.
[][]Place the drain tank under the discharge port.
[][]Ensure the discharge port is securely closed.
[][]Check again there is no material inside the container.
[][]Fill the container until half of the mixing chamber with normal water.
[][]Securely close the inlet port.
[][]Activate the machine to rotate at low speed first before accelerate the speed.
[][]After a while, check inside the chamber whether machine residue is fully dissolved and suspended or not. If not, start the blender rotation again.
[][]Repeat the procedure until it is done.
[][]Now discharge the water with dissolved materials.
[][]Now hot water is applied inside the chamber to remove materials fixed hardly on the chamber surface.
[][]Wash the machine with wet marking cloth.
[][]Re-wash the machine with purified water as required. Finally rinse with purified water.
[][]Clean inlet ports, discharge port, mixing chamber and external surface with damp cloths.
[][]Wipe the water droplets with cloth, and dry the machine with compressed air.
[][]Fix ‘CLEANED’ label on the machine.
[][]Keep the record of machine operation and cleaning according to the Annexure – I of this SOP.

Annexure:

Annexure – I: Operation and cleaning log sheet of Container Blender

Container blender operation and cleaning procedure Read More »

Wet and Dry Granulator Operation and Cleaning Procedure

Wet and Dry Granulator , Purpose:

Wet and Dry Granulator , The purpose of this SOP is to define the operation and cleaning procedure of Wet and Dry granulator.

Wet and Dry Granulator , Scope:

This SOP is applicable for operation and cleaning procedure of Wet and Dry granulator in product development of  XX Pharmaceuticals Limited.

Definition / Abbreviation:

[][]None

Responsibilities:

[][]The roles and responsibility are as follows

Operator/Supervisor Product Development

[][]Operation and cleaning of the Wet and Dry granulator
[][]Maintaining operation and cleaning log book

Executive/ Senior Executive, Product Development

[][]Checking and ensuring that the operation and cleaning is performed according to the SOP.
[][]Checking the log book.
[][]Preparation and timely review of the SOP.

Manager, Quality Assurance

[][]Ensure that the SOP reflects actual operation and cleaning procedure.
[][]Approve the SOP against XX Pharmaceuticals Limited master documents and current regulatory requirements.
[][]Implementation of the SOP.

Procedure:

[][]Machine Assembling
[][]Before operation assemble the machine accessories that are necessary for operation.
[][]Place the appropriate granulator head that is Wet head or Dry head.
[][]Place the appropriate sieve in the head.
[][]Securely lock the main head body to the driving shaft.
[][]Clamp down or tighten each component in place and insert the desired sieve with correct mesh size.
[][]Tightened the blade, hopper and body.
[][]Switch on the machine check that the granulation head rotates smoothly and there is no abnormal noise heard.

Machine Operation

[][]Switch on Main Breaker to supply main power to the system.
[][]Place a product container underneath the granulation head.
[][]Wrap the discharge chute with lint-free cloth which allows air to flow through. This will make the product flow penetrating into the product container without dispersing in the air.
[][]Press Start (Green push button) to activate the granulation head. The head will start rotating.
[][]Gradually load material into the granulation head from the top side.
[][]Observe that material loading rate should synchronize with granules output rate, that granule present through the discharge chute into the product collection bin.
[][]Loading product faster in the granulation head will results finer particles than the desired.
[][]The granulation rate varies depending on sieve size used and product characteristics.
[][]After charging all material into the machine and all are discharged, press Stop (Red push button) to discontinue the granulation process. The main shaft will stop rotating.

Machine Cleaning

[][]If the machine doesn’t used within 15 days after cleaning, then the machine should be cleaned on the 15th day.
[][]For safety purpose, cut off the main breaker that supply electricity to the machine before commencing the cleaning operation.
[][]Removing Granulation head from the main machine and bring it to the cleaning area.
[][]Disassemble each component for cleaning separately.
[][]Clean each component with fresh running potable water, hot water finally Purified water. Spatula (scraper) and cleaning agent might be required to remove sticky material attached on the surface.
[][]Do not submerge Granulation head into water bath. Water will penetrate into the bearing housing and cause rust, bearing service life of bearing will be lessened and machine will not operate smoothly.
[][]Spatula (scraper) or cleaning brush used with the machine must be made of only of plastic, rubber or materials that do not generate scratches or damage to the mirror-polished surface.
[][]Sieve should be thoroughly clean and ensure that no material stuck in the perforated holes and wire net.
[][]Repeat cleaning if necessary until the granulation head is completely cleaned.
[][]Use soaked cloth to clean the main granulation machine. Care must be taken that no water enters the control box and motor housing.
[][]Wipe each component with clean and dry cloth to remove the remaining water. Start wiping the critical area that is product contact parts first, following by non-product contact area.
[][]Apply compressed air or heated air to expedite the drying rate. Otherwise, leave each component to dry up in the clean operating room.
[][]Re-wash the machine with purified water as required. Finally rinse with purified water.
[][]Fix ‘CLEANED’ label on the machine.
[][]Keep the record of machine operation and cleaning according to the Annexure – I of this SOP.

Annexure:

Annexure – I: Operation and cleaning log sheet of Wet and Dry granulator

Wet and Dry Granulator Operation and Cleaning Procedure Read More »

Fluid Bed Processor Operation And Cleaning Procedure

Fluid Bed Processor, Purpose :

Fluid Bed Processor, The purpose of this SOP is to describe the operation and cleaning procedure of Fluid Bed Processor (Model: FBD 5) in order to comply with cGMP standard.

Fluid Bed Processor, Scope :

The scope of the procedure is applicable to the Fluid Bed Processor (Model: FBD 5) at the Product Development area of General block of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

None

Responsibilities:

The roles and responsibility is as follows:

Operator/Supervisor Product Development

[][]Operation and cleaning of the Fluid Bed Processor (Model: FBD 5).
[][]Maintaining operation and cleaning log book

Officer/ Sr. Officer, Product Development

[][]Checking and ensuring that the operation and cleaning is performed according to the SOP.
[][]Checking the log book.
[][]Preparation and timely review of the SOP.

Manager Engineering

[][]Preparation of maintenance schedule and maintenance of the machine.

Manager, Quality Assurance

[][]Ensure that the SOP reflects actual operation, cleaning and maintenance procedure.
[][]Approve the SOP against XX Pharmaceuticals Ltd. Master documents and current regulatory requirements.
[][]Implementation of the SOP.

Procedure:

[][]Machine Assembling
[][]Installation of finger type filter bag.
[][] Attach the filter bag with the filter bag lower clamp and tighten with a screw.

[][]Install compressed air line through pneumatic service unit, turn on the compressed air line and make sure that compressed air is regulated to 6 bar
[][]Release the emergency switch and turn on the main control, to supply electricity to the control panel
[][]Press filter Move down to lower the filter bag holder, clamp the clean filter bag to all hooks of the filter bag holder
[][]Press filter move Up to move to raise the filter bag holder up until in reaches the locking position
[][]Filter ba seal lamp illuminates in green to indicate that the filter bag is in locking position. If the filter bag is not locking in position the filter bag seal lamp illuminates red to indicate that the filter bag is not lock in properly.
[][]Test filter shaking to ensure that filter cleaning mechanism is functional.

Inlet air handling

[][]Inspect that pre-filter unit (EU4) of inlet air handling system is clean and does not clog.
[][]Check that there is no air leakage in the air handling and duct.
[][]Ensure that differential pressure across the medium filter is less than 2.0
[][]Check that differential pressure across the Hepa filter is less than 2.0

Exhaust air handling

[][]Check that there is no air leakage in the inlet air handling and duct
[][]Ensure that differential pressure across the dust collector is less than 2.0
[][]Ensure that differential pressure across the medium filter is less than 2.0
[][]Make sure that before starting the machine the drain valve and other ports are closed.
[][]Pneumatic service unit.
[][]Check lubrication level of air lubricator
[][]Drain water from air filter before the water level exceeds the upper limit.
[][]Inspect that there is no damage with pneumatic service unit and compressed air supply tubes
[][]Regulate main compressed air to approximately 6 bars.
[][]Check critical instrument calibration tags are still valid. If the calibration is expired, send the instruments for re-calibration.

Machine Operation

[][]Release the EMERGENCY SWITCH by pushing and turning it along the arrow head direction. Electricity will be connected to the electric control unit.
[][]Ensure that the main compressed air is regulated to 6 bar.
[][]Twist MAIN CONTROL OFF/ON selector. Then touchscreen would display, the cover page.
[][]Touch anywhere in the screen. This action leads user to Menu screen
[][]Load wet granules or other materials which need to dry into the fluid bed container
[][]Move the fluid bed container to align with the expansion air filter housing. The proximity sensor would locate the trolley position to ensure that it is in the correct position before lifting.
[][]Press CONTAINER button on the menu page. The system would lead user to container lift mode.
[][]At preliminary stage, system status are as follow
[][]Filter bag seal: OUT
[][]Container position: OUT
[][]Press ring seal: OUT
[][]Press CONTAINER UP button to raise the Fluid Bed container up until it is securely attached with the expansion/exhaust air filter housing.
[][]After the fluid bed container lifted to final position, system status would change to
[][]Filter bag seal: OK
[][]Container position: OK
[][]Press ring seal: OK
[][]Press exit to return to main page.
[][]Press DRY button at the Menu page. Dry Process Setting screen should appear on the screen.
[][]Set the following parameter by touching on the screen and push the pop-up numeric keys
[][]Heat Air Temp : Inlet heating air temperature in °C
[][]Overheat Temp : Overheat limit of inlet air in °C
[][]Heat Delay Time : Turn on the exhaust blower without heating for a while
[][]Drying Time : Desired drying time in min (minute). The system count the time only when the heating temperature is reached.
[][]Cooling Time : Time in min (minute) which the exhaust blower remains activated while the heating element is switched OFF.
[][]Filter Shake Interval : The time interval between each filter shaking in min (minute).
[][]Filter Shake Frequency : How many pulses of filter shaking required per interval
[][]After all dry parameters are set, press DRY PROCESS button to get into Dry Process screen.
[][]Press IAV to set the inlet air flap valve opening in % (percentage).
[][]The IAV setting range is 0 – 100 %.
[][]0 % : Fully close
[][]100 % : Fully open.
[][]Push DRY to turn on the exhaust blower and the heating system according to the Dry Parameter
Setting.
[][]For Spry Granulation, peristaltic pump as well as magnetic stirrer should be hook on to the system.
[][]Air Spray Pressure for spray can be set on Air Spray Pressure Regulator. Air Spray Pressure should be set around 0.5 – 1.0 bar (kg/cm2).
[][]SPRAY Pump Speed can set from 0 – 99 rpm at the peristaltic pump.
[][]For SPRAY AUTO, SPRAY direction [FIG.7] will be rotate CW. However, after stop SPRAY AUTO the peristaltic pump will rotate CCW for 5 sec to prevent any spray solution drop.
[][]For SPRAY MANUAL, press SPRAY MANUAL button on Dry Process page, then SPRAY PUMP MANUAL control will pop up. In this page, operator can manually control spray direction CW and CCW by pressing CW/CCW to Start/Stop pump direction. In addition, spray pump can be activate/ deactivate in this page by pressing SPRAY button. To exit SPRAY PUMP MANUAL press X button.

[][]Push SPRAY to turn start peristaltic pump to spray coating material to the granule. When the filter is
shake the Spray will automatically stop.
[][]LIGHT OFF/ON selector [No.10] can be twisted to ON so the spotlight is activated
[][]Drying Time in min (minute). Drying time show both Set Time (Green) and Actual time (Red). Drying time can be also set within this page. System only take into account the time when the actual inlet heating air temperature reaches the setting temperature.
[][]Cooling Time in min (minute). Cooling time show both Set Time (Green) and Actual time (Red). Cooling time can be also set within this page. System automatically turns off heater in the cooling phase.

[][]Heating coil becomes Red color while it is operating. It turns Yellow after inactivated.
[][]Lamp on Filter section turn ON while it is shaking.
[][]When the blower operates, Red lamp on the blower lights up.
[][]If Different pressure indicator that Finger-type filter is clog but it does not reach the shaking interval yet, press SHAKE to activate the filter shaking. To discontinue the filter shaking, repress SHAKE button one more time.
[][]Product sample can be collected through the provided sampling port to check product conditions.
[][]The drying proceeds until the setting time is reached, then the entire system would be automatically shut down.
[][]Press RESET to reset the timer values to zero.
[][]After the process is completed the filter will be shake as per set time and frequency or press SHAKE to clean the Finger type filter for a while
[][]Exit Dry Process and return to Menu page
[][]Press CONTAINER button Container Lift Screen appears on the touchscreen. Select CONTAINER DOWN. Then, seal and pneumatic cylinder system are released. Subsequently, the pneumatic cylinder system would lower the Fluid Bed container down.
[][]Remove Product Temperature Probe from the machine first.
[][]Remove the Fluid Bed container and dried product from the machine
[][]Press GRAPH button. GRAPH Screen appears on the touchscreen. GRAPH Screen record the following value.
[][]Overheat Alarm (ALARM)
[][]Inlet Air Temperature Set Point (SP: IAT)
[][]Inlet Air Temperature Present Value (PV: IAT)
[][]Product Temperature (PD: PDT)

Machine Cleaning

[][]If the machine doesn’t used within 15 days after cleaning, then the machine should be cleaned on the 15th day.
[][]Cleaning of exhaust air filter bag
[][]Press FILTER MOVE DOWN on Container Lift screen to lower the filter down. The exhaust filter bag holder will be released from the machine.
[][]Remove the filter bag from the holder.
[][]Use vacuum to remove the remaining product from the filter bag.
[][]Take the filter bag to cleaning area. Clean with potable water, use detergent if necessary
[][]Completely rinse the filter bag to remove any detergent present
[][]Clean with hot water and finally rinse with purified water.
[][]Dry the filter bag and take in a poly bag attach a cleaned label and store in machine change parts cabinet.

Cleaning of Product Container.

[][]Vacuum the remaining product from the product container.
[][]Use clean water to wash the product container and release the filthy water through the sampling valve. Use hot water as necessary
[][]Remove the bottom screen for extensive clean as necessary.
[][]Thoroughly clean the sampling valve and sight glass.
[][]Repeat the cleaning until the product container is completely cleaned.
[][]Rinse with purified water.
[][]Use damped cloth the clean the external surface of the product container

[][]Remove the water droplet with dry and clean cloth, starting with product contact surface first and follow by non-product contact.
[][]Apply heated air from the inlet air supplied through the electrical heater.
[][]Cleaning of expansion/exhaust air filter housing
[][]Vacuum the remaining product from the internal surface.
[][]Use damped cloth the clean the internal surface. Pay special attention to the seal area.
[][]Repeat the cleaning until the unit is totally clean.
[][]Use damped cloth to clean the external surface of the product container.
[][]Remove the water droplet with dry and clean cloth, starting with product contact surface first and follow by non-product contact.
[][]Apply heated air to completely dry both internal and external surface. It is also applicable to apply heated air from the inlet air supplied through the electrical heater.
[][]Inspect inside the Fluid Bed container and the Expansion/Exhaust filter housing chamber for cleanliness.
[][]Enter Dry Mode and use the heated air generated by the inlet air handling to dry the internal surface of the Fluid Bed Processor.
[][]Use damped cloth the clean the external surface of the machine as necessary.
[][]Wipe with dry cloth to remove remaining water from the external surface. Start wiping the critical area first.
[][]Dry the machine with heated air to expedite the drying rate. Otherwise, leaving the machine to dry up in the clean operating room.
[][]Once the cleaning is completed, attach a cleaned label in the machine

Annexure: Fluid Bed Processor

Annexure – I: Operation and cleaning log book.

Fluid Bed Processor Operation And Cleaning Procedure Read More »

High Speed Mixer Granulator Operation And Cleaning Procedure

High Speed Mixer Granulator, Purpose:

High Speed Mixer Granulator, The purpose of this SOP is to define the operation and cleaning procedure of high speed mixer granulator.

High Speed Mixer Granulator, Scope:

This SOP is applicable for operation and cleaning procedure of High Speed Mixer Granulator in product development of XX  Pharmaceuticals Ltd.

Definition / Abbreviation:

None

Responsibilities:

The roles and responsibility are as follows:

Operator / Supervisor Product Development

[][]Operation and cleaning of the High speed mixer granulator
[][]Maintaining operation and cleaning log book

Executive / Sr. Executive Product Development

[][]Checking and ensuring that the operation and cleaning is performed according to the SOP.
[][]Checking the log book.
[][]Preparation and timely review of the SOP.

Manager, Quality Assurance, Manager

[][]Ensure that the SOP reflects actual operation and cleaning procedure.
[][]Approve the SOP against XX Pharmaceuticals Ltd. master documents and current regulatory requirements.
[][]Implementation of the SOP.

Procedure:

[][]Machine Assembling
[][]Before operation assemble the machine change parts that are necessary for certain type of operation.
[][]Install the filter bag at the machine lid cover port for air discharge and install the filter bag housing. Attach the shaking ring with the filter bag.
[][]Ensure that the discharge port is closed.
[][]Install the feed hopper at the lid cover of the machine. Check for the proper working of the valve.

Machine Operation

[][]Install the compressed air line in the machine, open the compressed air valve and observe that the air pressure is not more than 4 Bar.
[][]Turn the machine ON/OFF switch (main switch at the right down corner of the machine) to ON. Control panel light will illuminate and the machine is ON
[][]Lift the lid cover manually to upward and fill with sufficient quantity of raw material (3-6 kgs)
[][]Down the lid cover manually and lock with the manual locking devices by pressing the locks downward. Check for the proper locking of the lead cover.
[][]Turn the pilot lamp switch right to ON the lamp and left to OFF the lamp

[][]Set the mixing time (as desired) at the electric timer unit manually. Timer display shows the time in XX min and XX Sec mode. Press the upper button (▲) of timer unit to increase the time and down button (▼) to decrease.
[][]Set the agitator and chopper RPM to desired value through the speed adjust nobs in the control panel. Rotate clockwise to increase the RPM and anticlockwise to decrease the RPM.
[][]Press the agitator ON button (green) to start the agitator and chopper ON button (green) to start the chopper. Look for the actual speed of the agitator and chopper at the display. [][]Adjust where adjustment is necessary.
[][]To OFF the agitator or chopper, push the agitator or chopper OFF button (red).
[][]To add binder solution or water, OFF the agitator and chopper. Pour the solution in to the feed hopper. ON the agitator or chopper as required and pull the feed hopper valve upward. [][]Push back the valve after the whole solution is added.
[][]To run the process more than its predetermined time. Reset the time after completion of the process. ON agitator and chopper again.
[][]To stop the machine immediately, Push the emergency button backward, machine will be stopped immediately. To release from emergency stop, rotate the emergency button clockwise and pull inward, light will illuminate and the machine is started.
[][]To check the granules during process. OFF the agitator and chopper. Shake the filter bag through filter bag housing. Wait at least for 1 minute to allow the powders to settle down and lift the machine lid cover manually.
[][]To discharge the granules after process completion of process. Rotate the discharge valve (at the back of the machine) clockwise, discharge chute will open automatically. To close the discharge chute rotate the valve anticlockwise.
[][]Place a poly bag or bowl at the discharge port to hold the discharging granules.
[][]Granules can be discharged both automatically and manually. Choice of the discharging process will depend on the granules condition.

[][]To discharge the granules automatically push the agitator ON button (green) by keeping the discharge valve open. When granules are discharged Push the OFF button (red). Open the lid cover and manually scavenge the remaining granules through the discharge port.
[][]To discharge the granules manually open the lid cover of the machine and manually pass the granules through the opening of discharge unit. Scavenge all granules manually.
[][]Turn the pilot limp button left to Off the pilot lamp.

Machine Dismantling

[][]Turn the machine ON/OFF button to OFF. The machine light will be OFF
[][]Remove the filter bag housing and the filter bag of the machine
[][]Remove the feed hopper from the machine

Machine Cleaning

[][]If the machine doesn’t used within 15 days after cleaning, then the machine should be cleaned on the 15th day.
[][]Cleaning of filter bag housing and feed hopper
[][]Clean the filter bag housing with clean markin cloth to remove solid and semisolid dusts
[][]Clean with potable water by rubbing with a cloth.
[][]Clean with damp cloth to remove any dust adhering to the parts.
[][]Clean with hot water and then with purified water.
[][]Soak with a clean dried markin cloth to remove the water from the parts
[][]Allow removal of all water and dry with compressed air.
[][]Wrap with poly bag, attach “CLEANED” label and store in the accessories cabinet.

Cleaning of filter bag

[][]Clean the filter bag with potable water.
[][]Soak the filter bag in detergent water and retain for 30 minutes
[][]Wash the filter bag 3 times by rubbing with potable water
[][]Wash the filter bag with hot water and finally with purified water.
[][]Squeeze the filter bag to remove water and allow to dry in the wash bay
[][]After drying take the filter bag in a poly bag, attach “CLEANED” label and store in the accessories cabinet.

Cleaning of the main machine

[][]Place the drainage tank under the discharge valve and make sure that the discharge port is closed.
[][]Make sure that air purging is between 1-2 bar.
[][]Open the lid and fill purified water until the chopper is flooded with water. Make sure that water bubbles come out from each shaft seals indicating that compressed air is supplied through the seals to protect water from penetrating into the driving unit.
[][]Close the lid and activate both agitator and chopper. Ensure that both agitator and chopper operate as normal.
[][]Be sure no purified water comes out through the lid seal.
[][]After a while, check inside the machine whether the product left in the bowl is dissolved into the purified water.
[][]Continue the agitator and chopper operation as necessary.
[][]Open the discharge valve to remove filthy water from the bowl into the tank
[][]Clean the inner parts, agitator and chopper of the machine with a damp cloth to remove any insoluble particle
[][]Rewash the machine with potable water in same procedure
[][]Rewash the machine with hot water and then with purified water following same procedure
[][]Clean the discharge valve, bowl and external surface with damp cloths.
[][]Wipe the water droplets with clean and dry cloth, and allow the machine to dry with compressed air.

 Annexure:

Annexure – I: Operation and cleaning log book.

High Speed Mixer Granulator Operation And Cleaning Procedure Read More »

Calibration of Hardness Tester with operation & cleaning

Calibration of Hardness Tester, Purpose :

Calibration of Hardness Tester, The purpose of this SOP (Standard Operating Procedure) is to describe the operation, calibration and cleaning of Hardness Tester.

Calibration of Hardness Tester, Scope :

This procedure is applicable for Hardness Tester (Model: ERWEKA, TBH125 ) used in Product Development Laboratory of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]PD: Product Development

Responsibilities:

The roles and responsibility is as follows:

Executive, PD

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Sr. Executive, PD

[][]To ensure that this procedure is kept up to date.
[][]To arrange training on the SOP to all concerned personnel.
[][]To ensure implementation of the SOP after training.

Manager, Quality Assurance

[][]Approval of the SOP.

Procedure:

Precaution(s):

[][]Check the power supply before connecting the machine.
[][]Keep the tester clean.
[][]Always switch off the machine at the end of work.

Operating Procedure:

[][]Turn on the power switch of Hardness Tester.
[][]After power on, the instrument is powered up and the following display will be shown:

ERWE

A TBH

UP DOWN

STOP FORWARD

UP DOWN …. Key

[][]Continue with Start/ Enter key, then following display will be shown:

ZERO

JAW

[][]Start zeroing with the Start/Enter key. The jaw will move to the counter-jaw, measure the Zero point, and then return to the initial position.

[][]The main menu will only be displayed if a correct zero point is detected.

NUM

0006

[][]Instrument Settings: In order to setup the instrument and enter configuration details and other parameters of the TBH125 instrument proceed as follows:
[][]Pause (PAUS):The pause time of the hardness tester between measurement cycles shall be entered using right arrow keys. Setting pause time will be 0-10 time units (approximately 10 seconds).
[][]Hardness (UNIH): Breaking force such as Newton, Strong Cobb or Kilopond by using the right arrow keys.
[][]Diameter and Thickness (UNID): Select mm or inch by using the right arrow keys.
[][]Hours (HOUR): Enter current time hours by using the right arrow keys.
[][]Minutes (MINU): Enter current time minutes by using the right arrow keys.
[][]Day (DAY): Enter current date by using the right arrow keys.
[][]Month (MONT): Enter current month by using the right arrow keys.
[][]Year (YEAR): Enter current year by using the right arrow keys.
[][]Newton Factor (NFCT): This internal calibration factor will be set by using the right arrow keys.
[][]Language (LANG): Language will be selected by using the right arrow keys.
[][]Auto On: Use the “Auto On” button to activate the automatic function of the diameter. This means that the nominal diameter needs not to be entered when measuring the diameter.
[][]Date Format (DAFT): Select date format in European or US format
[][]EURO = day : month : year
[][]USA = year : month : day
[][]By using left arrow keys.
[][]Method (METH): Select between the speed or force method for actual measurement by using the left arrow keys and then press Start/ Enter key.
[][]Hardness (HARD): By using the right arrow keys select whether the hardness measurement is going to be performed or not (on/off) and then press Start/ Enter key.
[][]Diameter (DIAM): By using the right arrow keys select whether the diameter measurement is going to be performed or not (on/off) and then press Start/ Enter key.
[][]Thickness (THIC): By using the right arrow keys select whether the thickness measurement is going to be performed or not (on/off) and then press Start/ Enter key.
[][]Speed (SPED): The speed of the breaking process can be set in millimeter per second, from 0.5 to 3 mm/s by using the right arrow keys. The default value is 2.3 mm/s.
[][]Force (FORC): The default value of force of the breaking process is 0020 N/s.
[][]Results (REST): When select “REST” a list of individual values appear, which will be stored until the instrument is switched off or a new test is run, and which can be printed again in the printer menu.
[][]Statistics (STAT): When selecting ‘STAT’ a statistic evaluation of the current test appears. It will be stored until the instrument is switched off or a new test is run, can be printed again in the printer

Calibration procedure:

[][]Ensure that the instrument is clean before use, including surrounding area.
[][]Check and ensure due date of calibration.

Diameter Calibration (DIAM):

[][]By Using Start/Enter key to select diameter.
[][]Clean the jaw and counter jaw with a brush and then press Start/ Enter key to start.
[][]The jaw moves to the counter jaw, measures zero point, and then returns to the initial position.
[][]A gauge block of 10.00mm is preset. Insert gauge block and start measurement using the Start/Enter key. The jaw moves to the gauge block and registers the second point.
[][]Three different control measures must be performed in succession to test the accuracy of the test station.
[][]A gauge block of 5.00mm is preset. Insert gauge block and start measurement using the Start/Enter key.
[][]The actual value will appear on the display, continue to the control measurement using the Start/ Enter key.
[][]Thickness Calibration (THIC): The thickness calibration is not applicable because of previously performed diameter calibration.

Hardness calibration (HARD):

[][]Select hardness using Start/Enter key.
[][]The calibration weight to be adjusted.
[][]The jaw moves to the calibration position and stop. The path is set in the menu COPS for the calibration position.
[][]Place mount calibration device on the jaw.
[][]Place the device with the weight receptacle on the right side while ensuring that the printer connection is free.
[][]The actual weight is displayed (not exactly zero because of the weight of the plate).
[][]Zero the device with the help of left and right arrow keys.
[][]Carefully placed the desired weight on instrument.
[][]Press Start/ Enter key to confirm and finish the calibration.
[][]The Linearity of the load cell is verified with three different control weights. Make sure that the weights are positioned carefully and stable on the plate.
[][]Use Start/Enter key to confirm. The actual is displayed. Use Start/ Enter key to continue.
[][]When calibration is finished remove the weighing plate and reposition the instrument. Use Start/ Enter key to confirm. The jaw moves back to origin.
[][]The display returns to calibration menu. When quitting the calibration menu with the key a calibration printout is performed automatically.

Calibration Frequency:

Cleaning procedure:

[][]Before starting each day operation, clean the overall instrument by a lint-free dry cloth.
[][]Clean the star feeder using a clean cloth.
[][]Use the brush to remove the tablet debris from the transport way after each operation.

Annexure:

Annexure-I: Log Book of Hardness Tester.

Calibration of Hardness Tester with operation & cleaning Read More »

BMR and BPR Preparation Standard Procedure

BMR and BPR Preparation, Purpose:

BMR and BPR Preparation, The purpose of this SOP is to define those details that need to be specified in, BMR & BPR to enable consistent routine manufacture and Packaging.

BMR and BPR Preparation, Scope:

This SOP is applicable for preparation of BMR and BPR of  XX Pharmaceuticals Limited.

Definition of Terms:

[][]BMR: Batch Manufacturing Record
[][]BPR: Batch Packing record

Responsibilities:

The roles and responsibility are as follows:

Senior Executive, Product Development

[][]Preparation of BMR and BPR following the SOP.
[][]Preparation and revision of validated BMR and BPR after completion of validation
[][]Preparation and timely review of the SOP.

Assistant Manager, Production

[][]Review of the BMR and BPR
[][]General manager, Plant
[][]Review of the BMR and BPR

Manager, Quality Assurance

[][]Approve the BMR and BPR
[][]Approve the SOP against XX Pharmaceuticals Ltd. master documents and current regulatory requirements.
[][]Implementation of the SOP.

Procedure:

[][]Procedure for preparation of Batch Manufacturing record (BMR)
[][]Select and confirm that the name and strength of the product and all the parameters related to BMR is correct.
[][]Follow the following procedure while preparing BMR
[][]A4 size paper
[][]Page orientation will be landscape
[][]Keep the top margin 0.2”, bottom margin 0.2”, Left margin 0.5”, Right margin 0.5”, gutter 0 and gutter position at left
[][]Keep the header and footer 0.2” from the edge
[][]Use Arial font
[][]Font size will be 10 unless or otherwise specified.
[][]Use Bold Capital letters inside third bracket for headings like Dispensing, Granulation etc
[][]Use Bold Capital letters for heading like Check before dispensing, Check before sieving, manufacturing instruction etc. Roman numerical numbers should be followed with the heading.
[][]Use normal Bold letters for any highlighting process
[][]Use arithmetic numerical numbers for all manufacturing instructions
[][]Use border line of two horizontal lines at every page.
[][]Include a table for prepared by, checked by and verified by after completion of all checking steps.
[][]Follow the following for header and footer
[][]Company logo will be standard sized at the top left corner of the page.
[][]Company Name will at the middle with all Capital letter, Bold and with font size 14.
[][]Company address will be at the middle with bold letters of font size 10.
[][]Place Batch Manufacturing Record at the middle in between company name and logo and signatory separated by two double lined horizontal line.
[][]Batch Manufacturing Record will be at the middle with all capital bold letters of font size 12.

Heading on the header will be

[][]Product Name
[][]Product Code
[][]Batch Size
[][]Version No
[][]Batch No
[][]Mfg Date
[][]Exp Date and
[][]Page number.
[][]With normal bold letters of font size 10.
[][]Product name will be normal bold letters of font size 12
[][]Signatory will have one prepared by, one checked by, three reviewed by and one approved option with normal, bold letters of font size 10.
[][]Designation, Department and date option of signatory will be of font size 10.
[][]Use effective date, revision date and revision history in first page.
[][]State a precaution (where applicable) and checking step prior to starting of any processing steps.
[][]Give a title for each stage such as room condition, machine setup etc. Title will be normal Bold letters with font size 10.
[][]Write all the instruction chronologically, sequentially, logically and in a clear way so that everyone can understand easily.
[][]Provide IPC parameters specification and checking sheet where applicable
[][]Provide a container summary record space at the end of the steps like compression and coating.
[][]Keep a reconciliation stage after each processing steps (eg. Granulation, compression etc.)
[][]Provide documents checking option of production and quality assurance head after completion of all stages.

Procedure for preparation of Batch Packing record (Primary Packing)

[][]Select and confirm that the name and strength of the product and all the parameters related to BPR is correct.
Follow the following procedure while preparing BPR
[][]A4 size paper
[][]Page orientation will be landscape
[][]Keep the top margin 0.2”, bottom margin 0.2”, Left margin 0.5”, Right margin 0.5”, gutter 0 and gutter position at left
[][]Keep the header and footer 0.2” from the edge
[][]Use Arial font
[][]Font size will be 10
[][]Use Bold Capital letters inside third bracket for headings like Primary Packaging
[][]Use Bold Capital letters for heading like material requisition, line clearance etc. Roman numerical numbers should be followed with the heading.
[][]Use normal Bold letters for any highlighting process
[][]Use arithmetic numerical numbers for all checking parameters
[][]Use bullet point for all checking options
[][]Use border line of two horizontal lines at every page.
[][]Include a table for performed by, checked by and verified by after completion of all checking steps.
[][]Follow the same procedure as described for header for BMR in case of BPR also
[][]Keep effective date, revision date and revision history in the first page of the BPR
[][]Put the following option in the BPR
[][]Material requisition sheet
[][]Line clearance record
[][]Machine setup section
[][]Record keeping action for setting up the machine
[][]In process checking parameters and record keeping option
[][]Destruction record keeping option
[][]Reconciliation stage after Packaging
[][]Provide documents checking option of production and quality assurance head after completion of all stages.
[][]Procedure for preparation of Batch Packaging Record (Secondary Packing)
[][]Select and confirm that the name and strength of the product and all the parameters related to BPR is correct.
[][]Follow the same page margin specification as were in the batch packaging record
[][]Follow the same procedure as described for header and footer for BMR in case of BPR also
[][]Keep effective date, revision date and revision history in the first page of the BPR
[][]Put the following option in the BPR
[][]Material requisition option
[][]Line clearance option
[][]Item checking before packaging option
[][]Machine setup option with record
[][]In process checking parameters and record keeping option
[][]Item check after packing
[][]Sampling summary
[][]Packaging material destruction record
[][]Reconciliation record
[][]Yield calculation option
[][]Batch reconciliation option
[][]Finished product transfer record

[][]Provide documents checking option of production and quality assurance head after completion of all stages.

Procedure for preparation of Batch Packaging Record (Physicians Sample)

[][]Follow same procedure as Batch Packing Area with the following exception
[][]Specify Physicians sample at the header of the BPR
[][]Do not keep any batch reconciliation and material transfer record in the BPR.

Annexure:

Annexure – I: Format of Batch Manufacturing Record (BMR)
Annexure – II: Format of Batch Packing Record (Primary Packaging)
Annexure – III: Format of Batch Packaging Record (Secondary Packaging)
Annexure-IV: Format of Batch Packaging Record (Physicians Sample)

BMR and BPR Preparation Standard Procedure Read More »

Waste Disposal Procedure For Product Development Area.

Waste Disposal, Purpose:

Waste Disposal, To describe the general waste disposal procedure in product development area.

Waste Disposal, Scope:

This SOP is applicable for general waste disposal procedure for product development area  of XX Pharmaceuticals Limited.

Definition of Terms:

None

Responsibilities:

The roles and responsibility are as follows:

Executive/ Sr. Executive Product Development

[][]Disposal of waste according to the SOP
[][]Preparation and timely review of the SOP.

Senior Executive, Quality Compliance

[][]Checking the disposal procedure at the time of operation

Head of Plant Operation

[][]Review the waste disposal procedure.

Head of Quality Assurance

[][]Approve the disposal activities.
[][]Implementation of the SOP.

Precaution(s):

[][]All concerned persons have to follow the SOP.
[][]Wear dust mask, safety goggles and rubber gloves during handling waste materials.
[][]Ensure that all containers are closed before sending for salvage.
[][]Keep a record in the log book for different wastes before destroying.
[][]Any deviation from the stated procedure should be documented and reported to the supervisor for corrective measure.

Waste Disposal, Procedure:

Waste originated during product development activities can be classified into five categories such as:
[][]Chemical Waste
[][]Plastic Waste
[][]Paper Waste
[][]Cotton Waste
[][]Broken/ fractured glass bottle

The rejected products shall be accumulated and stored separately in restricted areas with the label “To be destroyed”.

Chemical Waste (Solid, Blister and Liquids)

Solid waste:

[][]Solid waste consists of chemicals spread during different manufacturing stages such as: dispensing, charging, addition, de-dusting etc. These are also produced during Lab batches as the excess granules or tablet/capsule after keeping required quantities of the products for stability studies. These are disposed off as follows:
[][]Sweep off chemicals from the floor with the help of a vacuum cleaner or a brush and handy shovel and keep it in waste bin.
[][]Collect chemical dust from the collector of vacuum cleaner.
[][]Weigh and record it in a register. Fill the Annexure – I of the SOP and take approval for disposal from Manager, Quality Assurance.
[][] In presence of a Quality Compliance Officer dissolve the waste chemicals in water and pass through drain to ETP.
[][]After keeping required quantities of the products for stability studies, weigh the remaining quantities and record the quantity in a register.
[][]Fill the Annexure – I of the SOP and take approval for disposal from Manager, Quality Assurance.
[][]In presence of a Quality Compliance Officer dissolve the remaining granules and tablet/ capsule in water and pass through drain to ETP.

Blister waste:

Blisters containing tablets or capsules become waste after completion of stability studies at different conditions and storage periods and also after expiry date. These are disposed off as follows:
[][]Collect the waste blisters of different products and deblister them manually.
[][]Weigh the waste tablets /capsule and waste blisters.
[][]Record it in a register and Fill the Annexure – I of the SOP and take approval for disposal from Manager, Quality Assurance.

[][]In presence of a Quality Compliance Officer Dissolve the waste tablets /Capsule in water and pass through drain to ETP.
[][]Weigh and record the waste blisters in register book and then send to salvage yard.

Liquid waste:

[][]Liquid waste comprises mainly washings generated during cleaning of different equipment and trace of chemicals spilled during dispensing. All these are disposed off as follows:
[][]Dispose off the liquid waste through floor drain.
[][]Wipe the spillage with a wet cotton brush and dispose off the washings through floor drain. These washings will go through floor drain to Effluent Treatment Plant (ETP).

Plastic Waste

Returnable:

Returnable plastic waste comprises empty PVC drum/ cane of chemicals. All these are returned to store after destruction of labels.

Others:

[][]Other plastic waste comprises empty polyethylene bag, PVC tube, reject strip, broken plastic etc. All these are disposed off as follows
[][]Make it unusable by cutting. Keep them in waste bin.
[][]Weight the waste and record in a register.
[][]Fill the Annexure – I of the SOP and take approval for disposal from Manager, Quality Assurance.
[][]In presence of a Quality Compliance Officer send the waste to the salvage yard.

Paper Waste

[][]Expired documents/confidential company documents:
[][]Make it unusable by cutting Weight the waste and record in a register
[][]Fill the Annexure – I of the SOP and take approval for disposal from Manager, Quality Assurance.
[][]In presence of a Quality Compliance Officer send the waste to salvage yard.

Others:

[][]Paper waste comprises empty paper bag of raw materials, paper drums, rejected labels, leaflet, inner cartoons, shipper cartoons etc. All these are disposed off as follows:
[][]Make the waste unusable (except drum) by cutting and keep it in waste bin.
[][]Weigh and record it in a register. Fill the Annexure – I of the SOP and take approval for disposal from Manager, Quality Assurance.
[][]In presence of a Quality Compliance Officer send the waste for salvage.
[][]In case of drum, tear or destroy label. Weigh and record in the register book, then send to store
[][]Destroy paper bags, rejected labels, leaflets and inner cartoons by cutting.

Cotton waste

[][]Cotton waste consists of cotton bag of raw materials, unusable cotton duster etc. These are disposed off as follows
[][]Make the cotton waste unusable by cutting weight the waste and record in a register. Keep them in waste bin.
[][]Fill the Annexure – I of the SOP and take approval for disposal from Manager, Quality Assurance.
[][]In presence of a Quality Compliance Officer send the waste for salvage.

Broken/fractured glass bottle

[][]Break the unusable bottle by hammer with proper precaution, such as use mask, safety goggles, safety shoes, hand gloves and protective dress.
[][]Weigh and record in the register book.
[][]Weigh and record in the register book.
[][]Fill the Annexure – I of the SOP and take approval for disposal from Manager, Quality Assurance.
[][]In presence of a Quality Compliance Officer send the waste for salvage.
[][]All the waste disposal record forms must be stored in product development department and at the end of the year a total disposal summary will be provided to Manager, Quality Assurance.

Annexure: Waste Disposal

Annexure – I: Waste disposal request form.

Waste Disposal Procedure For Product Development Area. Read More »

Stability Study standard operating procedure

Stability Study, Purpose:

Stability Study, The purpose of this SOP is to define the procedures to be followed in the management of stability studies throughout the stability study lifecycle from study initiation to study completion.

Stability Study, Scope:

[][]This procedure is applicable for
[][]Development of New Product.
[][]Reformulation of existing products.
[][]Routine study of commercial batches.
[][]Change of specification of raw and primary packing material.
[][]Process change.
[][]Change of batch size.
[][]Rework reprocess and investigational batches.
of all pharmaceutical products  at XX Pharmaceuticals limited.

Definitions / Abbreviation:

Stability Studies:

[][]Long-term and accelerated (and intermediate) studies undertaken on Development and/or production batches according to a prescribed stability protocol to establish the shelf-life of an finished pharmaceuticals product.

Accelerated Testing:

[][]Studies designed to increase the rate of chemical degradation or physical change of an active substance or pharmaceutical product by using exaggerated storage conditions as part of the formal stability studies.

Long Term Testing:

[][]Stability studies under the recommended storage condition for the re-test period or shelf life proposed (or approved) for labeling.

Development-scale Batch:

[][]A batch of an FPP manufactured by a procedure fully representative of and simulating that to be applied to a full production-scale batch. For example, for solid oral dosage forms, a Development scale is generally, at a minimum, one-tenth that of a full production scale or 100 000 tablets or capsules, whichever is the larger; unless otherwise adequately justified.

Specification:

[][]A list of tests, references to analytical procedures, and appropriate acceptance criteria, which are numerical limits, ranges or other criteria for the tests described. It establishes the set of criteria to which an FPP should conform to be considered acceptable for its intended use.

Release Specification:

[][]The combination of physical, chemical, biological, and microbiological tests and acceptance criteria that determine the suitability of an FPP at the time of its release.

Shelf-life Specification:

[][]The combination of physical, chemical, biological, and microbiological tests and acceptance criteria that an FPP should meet throughout its shelf life.

Shelf-life:

[][]The period of time during which an FPP, if stored correctly, is expected to comply with the specification as determined by stability studies on a number of batches of the API or FPP. The shelf-life is used to establish the expiry date of each batch.

Expiry Date:

[][]The date given on the individual container (usually on the label) of a product up to and including which the API and FPP are expected to remain within specifications, if stored correctly. It is established for each batch by adding the shelf-life to the date of manufacture.

Bracketing:

[][]The design of a stability schedule such that only samples at the extremes of certain design factors, e.g. strength and package size, are tested at all time points as in a full design. The design assumes that the stability of any intermediate levels is represented by the stability of the extremes tested.

Matrixing:

[][]The design of a stability schedule such that a selected subset of the total number of possible samples for all factor combinations is tested at a specified time point. At a subsequent time point, another subset of samples for all factor combinations is tested. The design assumes that the stability of each subset of samples tested represents the stability of all samples at a given time point.

Container Closure System:

[][]The sum of packaging components that together contains and protects the dosage form. This includes primary packaging components and secondary packaging components, if intended to provide additional protection to the pharmaceutical product.

Responsibilities:

The roles and responsibility are as follows:

Senior Executive, Product Development

[][]Reporting and generation of stability protocol and stability report for new products
[][]Identify the need for stability study
[][]Sample storage and withdrawal.
[][]Compile and review the trend of analytical test results.
[][]Time to time revision of the SOP.
[][]Prepare Monthly Stability Schedule of new products.

Senior Executive, Quality Control

[][]Prepare, generate & Review Master Stability Schedule
[][]Timely analysis of stability sample and analytical report generation.
[][]Development and validation of finished products analytical method.

Senior Executive, Quality Assurance

[][]Sampling of the commercial batches for real time stability study.
[][]Schedule, reporting and generation of stability protocol and stability report for commercial products.

Head of Quality Assurance

[][]To approve the stability protocol and stability report.
[][]To approve the shelf life and packing instruction of the products to be marketed.

Procedure

Precaution:

All concerned persons have to follow the SOP. Keep The Stability Samples according to instruction and maintain Stability Schedule of individual Product.

Stability study of Development batches

Stability study protocol of Development batches

[][]Executive product development will generate he stability study protocol after completion of the trial batch of the products according to the Annexure I of this SOP
[][]Individual protocol will be used for individual products. In case of any change in the protocol, due to any stability problem, new version of the protocol will be issued, defining change history at the revision details section of the protocol.
[][]Each protocol will have a unique identification number of 20 digits. As following
GPD/SSP/001/XX/01
Where,
GPD stands for General Product Development. In case of Cephalosporin unit, the code will be CPD which indicates cephalosporin Product Development.
SSP stands for Stability Study Protocol.
001 in the numerical serial number, first protocol of the year will bear number 001, second one 002 and continue till the end of the year.
XX stands for the year 20xx, in case of the following years
01 stands for the version number. Second version will bear the number 02 and so on.
/ stands for separator in all case.

[][]Executive, Product Development will maintain a log Book according to Annexure II of the SOP to record the Protocol Number. Specific protocol shall be used for specific products and same number shall never be issued for two products.
[][]Senior executive, product development will check the protocol and Manager, Quality Assurance will approve the protocol.

Determining Batch Size

[][]Executive, Product Development will determine the batch size of the products. Batch size of the Development batches will be one tenth of the commercial batch. Commercial batch size will be determined from the yearly sales forecast. Depending on the sales volume, the commercial batch size will be either 50 kg or 30 kg. Therefore, Development batch size will be either 5.0 kg or 3.0 kg respectively.

Design of stability Study

For new product stability study, one trial batch and two Development batches will be stored for stability study, also optimization and validation batches will be stored for stability testing.

[][]1 Trial batch
(batch size: Below 1 kg or decided batch size)

[][]2 Development batches
(batch size: 1/10th of Commercial batches)

[][]Commercial Batches (Ongoing)

Reformulation manufacturing / Process change / Specification Change (API / Excipient) , one trial batch and two Development batch will be stored for stability study, also optimization and validation batches will be stored for stability testing.

[][]1 Trial batch
(batch size: Below 1 kg or decided batch size)

[][]1 Development batch
(batch size: 1/10th of Commercial batches)

[][]Commercial Batches (Ongoing)
(Accelerated & Long Term)

New Source Development (Primary Packaging Material) / Equipment Change

[][]Trial run with new packing material / equipment

[][]Accelerated Stability study on Commercial batches

Number of sample to be stored

Executive, Product Development will store required quantity of sample according to the dosage form .In case of matrixing number of sample to be stored will be generated from the protocol.

Storage condition

[][]Storage condition of stability sample should be as per WHO assigned climatic Zone which is mentioned below:

Climatic ZoneAcceleratedLong term
Zone I40°C ± 2°C/75% R.H. ± 5% R.H.21°C ± 2°C/45% R.H. ± 5% R.H.
Zone II40°C ± 2°C/75% R.H. ± 5% R.H.25°C ± 2°C/60% R.H. ± 5% R.H.
Zone III40°C ± 2°C/75% R.H. ± 5% R.H.30°C ± 2°C/35% R.H. ± 5% R.H.
Zone IVA40°C ± 2°C/75% R.H. ± 5% R.H.30°C ± 2°C/65% R.H. ± 5% R.H.
Zone IVB40°C ± 2°C/75% R.H. ± 5% R.H.30°C ± 2°C/75% R.H. ±5% R.H.

[][]In case of storage in refrigerator (2°C – 8°C) indicated products storage condition and minimum testing time should be maintained as

StudyStorage conditionMinimum time period
Long term50 C ± 30 C12 months
Accelerated250C ± 20C / 60 ± 5% RH06 months

[][]In case of storage in freezer (-20°C ± 5°C) indicated products storage condition and minimum testing time should be maintained as  Long term storage condition shall be  (-200 C ± 50 C) for 12 months.

[][]As per WHO guideline Bangladesh is in Zone IVA. So, the stability study shall be done as per Zone IVA for the products marketed in Bangladesh only.
[][]Executive, Product Development will store the sample in the following conditions and for mentioned time period (at minimum) for initial submission to drug authority.

StudyStorage conditionMinimum time period covered by data at submission to Regulatory
Long term30°C ± 2°C/65% R.H. ± 5% R.H.12 months
Accelerated40°C ± 2°C/75% R.H. ± 5% R.H.6 months

[][]If 30°C ± 2°C/65% R.H. ± 5% R.H. or 30°C ± 2°C/75% R.H. ±5% R.H. is the long term condition there is no intermediate condition.

Bracketing

[][]Bracketing can only be done if the following criteria is meet
[][]Three or more strength of the products are to be stored for stability.
[][]Products are prepared by the same blend or same pellets by only varying the final weight.
[][]Packing materials for all strength are same.
[][]If all the above mentioned criteria are met, Executive, Product development will specify the bracketing design in the section 10 of the stability protocol.
[][]If applied shelf life for all strength will be declared by only assessing the minimum and maximum strength of the product. For example, if a tablet dosage form has three different strengths like 20 mg, 40 mg and 80 mg, only 20 mg & 80 mg strength may be selected for conducting stability study at all time points. The intermediate strength will then be represented by the stability of the extremes tested.

Matrixing

[][]The following factors can typically be matrixed
Strength (same formulation)
Container size
Container fill sizes
Intermediate time points
[][]The following factors should not be matrixed
Initial and final time points
Test parameters e.g. assay, related substances, pH
Dosage forms
Strength of significantly different formulation
Storage condition

[][]Bracketing and matrixing should not be applied together.
[][]Accelerated storage condition should not be matrixing, only long time test frequency may be matrixed.
Matrixing can be done in batches of the same formulation that are manufactured using same process and same machineries.
[][]Certain batches will be exempted from analysis at certain time point. but following time points must be considered for full scale analysis
Initial time point
06 Month time point
24 month time point with 18 month time point in case of the products with 18 month shelf life.

[][]Executive, Product Development will define the matrixing design at the section 10 of stability protocol.

Storage of stability sample

[][]A sample will be considered for stability storage if it meets the following criteria
[][]Batches prepared by same formulation using API from the same source
[][]Batches prepared using same manufacturing process and machinaries
[][]Batches meeting all specification as outlined in section 11 of the stability protocol
[][]Batches packed in the same container closer system

[][]After approval of the stability protocol, executive, product development will store the necessary quantity of sample  in the stability chamber.
[][]Executive product development will maintain the log book of stability sample storage log book (Annexure III).
[][]Individual log book would be maintained for individual stability chamber.
[][]Chamber number, tray number and position of sample stored must be mentioned clearly in the log book.
[][]Stability chamber tray is numbered numerically from 1 to 8 from top to bottom.

Tray and position number like 1A denotes that the sample is stored in 1st tray and in the rear left position of the tray.

Monthly stability schedule

[][]After storing sample in the stability chamber, executive, product development will entry the product name in the stability schedule. (Annexure IV)
[][]Stability schedule will be printed monthly from the live data, and will be stored in the stability chamber room at the beginning of the month.

Withdrawal of stability sample

[][]Based on the stability schedule, operator, product development will withdraw sample from the specific stability chamber.
[][]Sample will be withdrawn on due date whenever possible, but in case of any circumstance sample may be withdrawn within 7 days after the storage date. No sample will be withdrawn before the expected sample withdrawal date.
[][]After withdrawal of every sample, operator, product development will sign in the sample storage log book.
[][]Executive, product development will assign unique lab control number in every sample and maintain the stability sample analysis register (Annexure V) of this SOP.
[][]Executive, product development will analyze the sample and put the report in product master file, he will also put the data in stability trend.(Annexure VI)
Stability study report of Development batches.
[][]After completion of both the accelerated and long term stability testing executive, product development will generate a stability study report according to the Annexure VII of this SOP.
[][]Each report will have a unique identification number of 20 digit. As following
GPD/SSR/001/15/01
Where,
GPD stands for General Product Development. In case of Cephalosporin unit the code will be CPD which indicates cephalosporin Product Development.
SSR stands for Stability Study Report.
001 in the numerical serial number, first protocol of the year will bear number 001, second one 002 and continue till the end of the year.
15 stands for the year 2015, in case of the following years 16, 17 etc will be used.
01 stands for the version number. Second version will bear the number 02 and so on.
/ stands for separator in all case.

[][]Executive, Product Development will maintain a log Book according to Annexure VIII of the SOP to record the Report number. Specific report shall be used for specific products and same number shall never be issued for two products.
[][]Senior executive, product development will check the report and manager, Quality Assurance will approve the report.
[][]One copy of the report will be provided to quality compliance department for assigning shelf life to the commercial batches.
[][]One copy of the stability report will be generated to the regulatory department for regulatory submission.

Stability study of market sample

[][]A comparative study with the market sample will be done in case of all new products.
[][]Executive, product development will raise requisition for the amount of market sample required to supply chain department.
[][]Executive, product development will store the market sample in stability chamber with the stability batches.
[][]Only accelerated stability study will be done for comparison with the market sample.

[][]Executive, product development will send the sample of market products with the SAF along with the stability batches.
[][]Executive, product development will assign a unique lab control number to the SAF and analyze the sample.
[][]After analysis the analytical reports will be stored in the market products file and the analytical data will be entered in the stability trend (Annexure VI)
[][]After completion of the accelerated stability study a comparative result of the Development batch and market sample will be provided with the accelerated stability report.

Stability study of commercial batches

[][]Stability study protocol of commercial batches

[][]Commercial batches that will undergo stability study are as follows

Batches Accelerated studyLong term study
Optimization batches Y--
Validation batches YY
Change in the source of active raw materials: First three batchYY
Change in the source of major excipients: First batch. (Only if the excipients constitute more than 70 % of the total mix)Y--
Change in manufacturing process: First three batch after changeYY
Change in manufacturing equipment: First three batches after change.YY
Change in manufacturing formula: First three batches after change.YY
Change in batch size.YY
Reprocess / Rework batch: Specific batch.Y--

Y indicates the type of stability study to be conducted. Indicates no stability will be done for this storage condition.

[][]Executive, quality compliance will generate stability study protocol (Annexure I) of commercial batches
[][]Each protocol will have a unique identification number of 20 digit. As following
QCOM/SSP/001/15/01
Where,
GQCOM stands for G Block Quality Compliance.
SSP stands for Stability Study Protocol.
001 in the numerical serial number, first protocol of the year will bear number 001, second one 002 and continue till the end of the year.
15 stands for the year 2015, in case of the following years 16, 17 etc will be used.
01 stands for the version number. Second version will bear the number 02 and so on.
/ stands for separator in all case.

 

[][]Assistant manager, quality Assurance  will check the protocol and manager, quality compliance will approve the protocol.
[][]The protocol will be generated by keeping the batch number portion of the protocol blank. Executive, quality compliance will fill the portion while he will store certain batches in stability.
[][]Long term stability testing will continue for shelf life plus one year, for example if the product is assigned with 24 month shelf life tehn the study will be designed for 24 plus 12 that is for 36 month.

Storage of stability sample

[][]After approval of the stability protocol, executive, quality compliance will send the required quantity of sample to product development department along with the protocol and stability sample.
[][]Executive, product development will receive the sample and store the sample in the stability chamber after filling the log book (Annexure III)

Monthly stability schedule

[][]After storing the stability samples, executive, product development will fill the stability schedule (Annexure IV).
[][]At the beginning of the month executive, product development will print the schedule for the specific month and after signing from the department in charge send the schedule to quality compliance department.

Withdrawal of stability sample

[][]Executive, Quality Assurance will generate a Sample Advice Form (SAF) to product development department, based on the stability schedule.
[][]The SAF should be sent on due date, but due to any circumstance it may be sent after the expected date, no sample will be withdrawn before the schedule date.

[][]After receiving the Sample Advice Form from operator, product development will withdraw the sample and provide the sample to quality compliance department. He will sign in the logbook for sample withdrawal.
[][]Executive, quality Assurance will send the Sample Advice Form from along with the sample to quality control department.
[][]Executive, quality control will receive the sample and assign a unique lab control number and analyze the sample. After analysis executive, quality control will store the data in quality control department and put the result in stability trend.

Stability study report of commercial batches

[][]After completion of the accelerated and long term stability study executive quality compliance will generate the stability study report according to Annexure VII of this SOP.
[][]Each report will have a unique identification number of 20 digit. As following
QA/SSR/001/XX/01
Where,
QA Quality Assurance
SSR stands for Stability Study Report.
001 in the numerical serial number, first protocol of the year will bear number 001, second one 002 and continue till the end of the year.
XX stands for the year 20XX, in case of the following years
01 stands for the version number. Second version will bear the number 02 and so on.
/ stands for separator in all case.
[][]Senior executive, product development will check it and assistant manager quality compliance will review. Manager quality assurance will approve the report.
Significant change criteria“Significant change” for an Finished Pharmaceutical Products are:
[][]A change from the initial content of API(s) of 5% or more detected by assay, or failure to meet the acceptance criteria for potency when using biological or immunological procedures.
[][]Any degradation product exceeding its acceptance criterion.
[][]Failure to meet the acceptance criteria for appearance, physical attributes and functionality test
[][]Also, as appropriate for the dosage form:
[][]Failure to meet the acceptance criterion for pH; or
[][]Failure to meet the acceptance criteria for dissolution for 12 dosage units.

Data evaluation procedure

[][]In general, a provisional shelf-life of 24 months will be established provided the following conditions are satisfied:
[][]The API is known to be stable (not easily degradable).
[][]Stability studies, of API, have been performed and no significant changes have been observed.
[][]Supporting data indicate that similar formulations have been assigned a shelf-life of 24 months or more.
[][]Long-term studies to be continued until the proposed shelf-life has been covered, and the results obtained will be submitted to the national medicines regulatory authority.
[][]Alternatively, after the availability of sufficient long term data, shelf life will be declared following any of the following process:
[][]If the Accelerated stability data shows no significant change, the long term data shows little or no variability and the accelerated data also shows little or no variability then shelf life will be declared as double the time of available long term data but, it should not exceed long term data availability time + 12 month (Y = 2X, but should not exceed Y = X + 12 Month, Where Y = proposed shelf life, and X = period covered by long term data). Such as if a product meets all the above criteria with 12 month long term data, then shelf life will be 2 x 12 = 24 Month. If 24 month long term data will be available, shelf life will be 24 + 12 = 36 month but not 24 x 2 = 48 month.

[][]If accelerated data shows significant change, but long term data shows no significant change and shows little or no variability, a statistical analysis will be performed with graphical representation with 5% upper and lower acceptance criteria. Available data will be then extrapolated to figure out time to attain the lower acceptance criteria.

[][]If backed by the above graphical representation shelf life will be declared as 1.5 time of available long term data but, it should not exceed long term data availability time + 6 month (Y = 1.5X, but should not exceed Y = X + 6 Month Where Y = proposed shelf life, and X = period covered by long term data). Such as if a product meets all the above criteria with 12 month long term data, then shelf life will be 1.5 x 12 = 18 Month. If 24 month long term data will be available, shelf life will be 24 + 6 = 30 month but not 24 x 1.5 = 36 month.

[][]If the Accelerated stability data shows no significant change, the long term data shows variability and the accelerated data also shows little or no variability a statistical analysis will be performed with graphical representation with 5% upper and lower acceptance criteria. Available data will be then extrapolated to figure out time to attain the lower acceptance criteria.

[][]If backed by the above graphical representation, shelf life will be declared as double the time of available long term data but, it should not exceed long term data availability time + 12 month (Y = 2X, but should not exceed Y = X + 12 Month Where Y = proposed shelf life, and X = period covered by long term data). Such as if a product meets all the above criteria with 12 month long term data, then shelf life will be 2 x 12 = 24 Month. If 24 month long term data will be available, shelf life will be 24 + 12 = 36 month but not 24 x 2 = 48 month.

[][]If sufficient data are not available to perform the statistical analysis shelf life will be declared as 1.5 time of available long term data but, it should not exceed long term data availability time + 6 month (Y = 1.5X, but should not exceed Y = X + 6 Month Where Y = proposed shelf life, and X = period covered by long term data). Such as if a product meets all the above criteria with 12 month long term data, then shelf life will be 1.5 x 12 = 18 Month. If 24 month long term data will be available, shelf life will be 24 + 6 = 30 month but not 24 x 1.5 = 36 month.

[][]If the Accelerated stability data shows no significant change, the long term data shows variability and the accelerated data also shows variability a statistical analysis will be performed with graphical representation with 5% upper and lower acceptance criteria. Available data will be then extrapolated to figure out time to attain the lower acceptance criteria.

[][]If backed by the above graphical representation, shelf life will be declared as double the time of available long term data but, it should not exceed long term data availability time + 12 month (Y = 2X, but should not exceed Y = X + 12 Month Where Y = proposed shelf life, and X = period covered by long term data). Such as if a product meets all the above criteria with 12 month long term data, then shelf life will be 2 x 12 = 24 Month. If 24 month long term data will be available, shelf life will be 24 + 12 = 36 month but not 24 x 2 = 48 month.

[][]If sufficient data are not available to perform the statistical analysis shelf life will be declared as 1.5 time of available long term data but, it should not exceed long term data availability time + 6 month (Y = 1.5X, but should not exceed Y = X + 6 Month Where Y = proposed shelf life, and X = period covered by long term data). Such as if a product meets all the above criteria with 12 month long term data, then shelf life will be 1.5 x 12 = 18 Month. If 24 month long term data will be available, shelf life will be 24 + 6 = 30 month but not 24 x 1.5 = 36 month.

Labeling statement for finished product

[][]As the accelerated storage condition is 40°C ± 2°C/75% R.H. ± 5% R.H, and the long term storage condition is 30°C ± 2°C/65% R.H. ± 5% R.H. then the storage condition in final pack should include “ Do not store above 30°C”.
[][]Semi-finished and ready to fill materials
[][]In case of semi-finished and ready to fill material shelf life will be based on manufacturers declared shelf life regardless of date of dispensing.

Photostability Testing

[][]Selection of product/batch
[][]Photostability testing will be conducted for the finished products of which photo sensitivity is known. Products that are not photosensitive will not fall under the criteria of photo stability testing Photostability will be done for the Development batches and the validation batches only.
[][]Photostability will be conducted in following cases
[][]For new products
[][]Any change in the formulation
[][]Any change in the immediate pack
[][]Any change in the marketing pack
[][]From the three Development and trial batch, one Development batch will be stored for photostability, if the result from one batch is not conclusive then two other batch will be stored for photostability.
[][]From the three validation batch, one batch will be stored for photostability, if the result from one batch is not conclusive then two other batch will be stored for photostability.

Design of photostability

[][]Products will be stored in three following types
[][]Fully exposed products (products without any packing, coated if coating is incorporated)
[][]Products in immediate pack (eg. Blister or glass bottle or vial, ampoule)
[][]Products in the marketing pack (eg. Inner carton)
[][]Along with a controlled sample, this will be covered with aluminum foil to assure complete protection light.

Photostability testing protocol of Development batch

[][]Executive, product development will generate photostability testing protocol of Development batch according to Annexure IX of this SOP
Individual protocol will be used for individual products. In case of any change in the protocol, due to any stability problem, new version of the protocol will be issued, defining change history at the revision details section of the protocol.
[][]Each protocol will have a unique identification number of 20 digit. As following
PD/PSP/001/XX/01

Where,
PD stands for Product Development.
PSP stands for photo stability protocol.
001 in the numerical serial number, first protocol of the year will bear number 001, second one 002 and continue till the end of the year.
XX stands for the year 20X, in case of the following years
01 stands for the version number. Second version will bear the number 02 and so on.
/ stands for separator in all case.
[][]Executive, Product Development will maintain a log Book according to Annexure X of the SOP to record the Protocol Number. Specific protocol shall be used for specific products and same number shall never be issued for two products.
[][]Senior executive, product development will check the protocol and Manager, Quality Assurance will approve the protocol.

Number of sample to be stored

Number of sample stored will follow the following criteria

[][]Sample type/Number of sample
[][]Fully exposed sample /60 pcs
[][]Sample in immediate pack /60 pcs
[][]Sample in marketing pack /60 pcs
[][]Controlled sample /60 pcs

Sample storage procedure

[][]Executive, product development will store sufficient sample in the stability chamber after approval of the protocol
[][]He will provide input in the photostability sample storage log book (Annexure XI), he will provide input regarding the sample withdrawal time at the same time.
[][]Time requirement for sample to be stored should be calculated based on the procedure outlined

Withdrawal of sample

[][]Executive, product development will input the required time in photostability sample storage log book, in case of withdrawal time falling in the off time sample will be withdrawn at next possible time, no sample will be withdrawn before the schedule time.
[][]Operator, product development will OFF the light and withdraw the sample at scheduled time, and after wraping the sample with light protected barrier provide the sample for analysis.

Storage condition and procedure

[][]Executive, product development will define the position number in the tray, the tray is divided in supplied  position
[][]Executive, product development will define the position of each sample in the protocol from the above figure.
[][]He will ON the flurosence lamp and the UV lamp and take three reading of the flurosence light and UV light and from the average data will calculate the time required to attain the sufficient exposure time from the following equation

[][]Time required for flurosence light (H) = 1.2 x 1000000 / average data
[][]Time required for UV light (H) = 200 x 1000000 / average data x 10000
[][]After estimating the required time, executive, product development will determine when UV light will be kept OFF and when the sample will be withdrawn.
[][]Executive, product development will take reading of the both light twice daily, within the scheduled time at 8.30 AM in the morning and 4.30 PM in the evening, to figure out the actual values of light during sample stored.
[][]He will note the values daily in the photostability testing protocol.

Analysis of sample

[][]Executive, product development will analyze the samples along with the controlled sample after the end of the exposer time.
[][]In case of Tablet or Capsule a composite sample of 20 pcs will be analyzed.
[][]In case of other samples (eg. Suspension or vial/ampoule) homogeneous sample must be used for determination.
[][]Following test parameters will be tested after the exposed time
[][]Appearance
[][]Assay
[][]Degradants
[][]Clarity or color of solution (for suspension and vial/ampoule)
[][]Disintegration and dissolution for tablet and capsules.
[][]After completion of the analysis, executive, product development will submit the analytical result for evaluation.

Photostability testing report of Development batch

After completion of both the accelerated and long term stability testing executive, product development will generate a stability study report according to the Annexure II of this SOP.

[][]Each report will have a unique identification number of 20 digit. As following
PD/PSR/001/XX/01
Where,
PD stands for Product Development.
PSR stands for photostability study report.
001 in the numerical serial number, first protocol of the year will bear number 001, second one 002 and continue till the end of the year.
15 stands for the year 20XX
01 stands for the version number. Second version will bear the number 02 and so on.
/ stands for separator in all case.
[][]Executive, Product Development will maintain a log Book according to Annexure X of the SOP to record the report number. Specific report shall be used for specific products and same number shall never be issued for two products.
[][]Senior executive, product development will check the report and manager, quality assurance will approve the report.
[][]One copy of the report will be provided to quality compliance department for assigning shelf life to the commercial batches.
[][] Photostability study protocol of commercial batch
[][]Executive, quality compliance will generate photostability testing protocol of commercial batch according to Annexure VIII of this SOP
[][] Individual protocol will be used for individual products. In case of any change in the protocol, due to any stability problem, new version of the protocol will be issued, defining change history at the revision details section of the protocol.
[][]Each protocol will have a unique identification number of 20 digit. As following
QA/PSP/001/XX/01
Where,
QA stands for Quality Assurance
PSP stands for photo stability protocol.
001 in the numerical serial number, first protocol of the year will bear number 001, second one 002 and continue till the end of the year.
XX stands for the year 20XX.
01 stands for the version number. Second version will bear the number 02 and so on.
/ stands for separator in all case.
[][] Executive, Quality Assurance will maintain a log book according to Annexure XIII to record the report number. Specific protocol shall be used for specific products and same number shall never be issued for two products.
[][]Assistant manager, Quality Assurance will check the protocol and Manager, Quality Assurance will approve the protocol.
[][]Quantity of sample stored will be same as the section 7.7.4 of this SOP, storage conditions will be same as the section 7.7.5 of this SOP
[][]Storage of stability sample
[][]After approval of the stability protocol, executive, quality compliance will send the required quantity of sample to product development department along with the protocol and stability sample.
[][]Executive, product development will receive the sample and store the sample in the photo stability chamber after filling the log book.
[][] Withdrawal of stability sample
[][]Executive, quality compliance will generate a Sample Advice Form (SAF) to product development department, based on the stability schedule.
[][] The SAF should be sent on due date, but due to any circumstance it may be sent after the expected date, no sample will be withdrawn before the schedule date.
[][]After receiving the SAF operator, product development will withdraw the sample and provide the sample to quality compliance department.
[][]Executive, quality assurance will send the SAF along with the sample to quality control department.
[][] Executive, quality control will receive the sample and assign a unique lab control number and analyze the sample. After analysis executive, quality control will store the data in quality control department and put the sample in stability trend.

Photostability study report of commercial batch

[][]After completion of the photostability study executive quality compliance will generate the stability study report according to Annexure – IX of this SOP.
[][]Each report will have a unique identification number of 20 digit. As following
QA/PSR/001/XX/01
Where,
QA stands for General Quality Assurance.
PSR stands for Photostability study report.
001 in the numerical serial number, first protocol of the year will bear number 001, second one 002 and continue till the end of the year.
15 stands for the year 20XX
01 stands for the version number. Second version will bear the number 02 and so on.
/ stands for separator in all case.
[][] Senior executive, product development will check it and assistant manager quality compliance will review. Manager quality assurance will approve the report.
[][]Evaluation of data
[][]Sample data will be evaluated against the data of the controlled sample for any change in samples.
[][] Depending on the extent of change special labeling or packaging will be designed to mitigate exposure light.

Labeling information

Depending on the extent of change storage information like “Protect from light” will be incorporated in the marketing pack.

Annexure:

Annexure – I : Stability study protocol.
Annexure – II : Stability study protocol log book for Development batch.
Annexure – III : Stability sample storage log book.
Annexure – IV : Monthly stability schedule.
Annexure – V : Stability Sample analysis register.
Annexure – VI : Stability trend.
Annexure – VII : Stability study report.
Annexure – VIII : Stability study report log book for Development batch.
Annexure – IX : Photostability study protocol of Development batch.
Annexure – X : Photostability protocol logbook of Development batch.
Annexure – XI : Photostability sample storage log book.
Annexure – XII : Photostability study report of Development batch.
Annexure – XIII : Photostability report log book of Development batch.

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correspondence with regulatory affairs

Correspondence with regulatory affairs , Purpose:

Correspondence with regulatory affairs , The purpose of this SOP is to describe the procedures of the following activities related with the regulatory affairs, Namely
[][]Recipe preparation
[][]Annexure Preparation
[][]Sample sending procedure to DGDA for INN Products.
[][]Annexure amendment as and when necessary.
[][]To comply with the cGMP as well as DGDA requirements.

Correspondence with regulatory affairs , Scope:

This procedure is to be followed for recipe preparation, Annexure preparation, sample sending to DGDA for INN products and Annexure amendment procedure in of XX Pharmaceuticals Limited.

Definition of Terms:

[][]SOP: Standard Operating Procedure
[][]DA: Drug Administration
[][]INN: International Nonproprietary Name
[][]cGMP: Current Good Manufacturing Practice.
[][]QA: Quality Assurance
[][]QC: Quality Control
[][]PD: Product Development
[][]RA: Regulatory Affairs
[][]SCM: Supply Chain Management
[][]COA: Certificate of Analysis
[][]MOA: Method of Analysis
[][]W/S: Working Standard

Responsibilities:

The roles and responsibility are as follows:

Executive / Sr. Executive, PMD

[][]Generation of recipe.
[][]Generate pack size and brand name of the products.

Executive / Sr. Executive, Product Development

[][]Recipe and Annexure Preparation after completion of stability study
[][]Provide sample and stability data of INN products for submission to DA
[][]Provide Annexure amendment form and other related documents for Annexure amendment

Manager, Regulatory Affairs

[][]Recipe, Annexure, INN product sample and Annexure amendment form Submission to DA and provide approved recipe to QA
Update to QA, PD about any changes or requirements of DA

Executive / Sr. Executive, Quality Control

[][]Analysis of INN product sample send to DA

Head of Plant Operation

[][]Review Recipe and Annexure prior send to DGDA

Head of Quality Assurance

[][]Review the Recipe and Annexure prior send to DGDA.
[][]Approve the SOP against XX Pharmaceuticals Ltd. master documents and current regulatory requirements.
[][]Implementation of the SOP

Precaution(s):

[][]All concerned persons have to follow the SOP.
[][]Any deviation from the stated procedure should be documented and reported to the supervisor for corrective measure.

Procedure:

[][]Procedure for product proposal and feasibility testing
[][]PMD will generate the Recipe after finalization of product brief and based on technical feasibility.
[][]Recipe will be submitted according to the Annexure – I of this SOP
[][]Executive / Sr. Executive, PMD will fill the product data sheet and the section 6 and 7 of the Annexure and send to Product Development Department.
[][]Executive / Sr. Executive, Product development will fill the technical data section of the Recipe carefully and send the Recipe to GM Plant for further checking and signing in the particular section.
[][]After signing Product development will send the recipe to Head of QA for checking and signing in the particular section.
[][]After approval of the Recipe regulatory affairs shall conform to QA about the approval.
[][]Procedure for Annexure Preparation
[][]Necessary documents to be provided for product inclusion includes
Application for new product inclusion to the director of DA
Recipe approval form from DA
Product Inclusion fee
For INN products necessary quantity of sample (as described by DA) and analytical method of the product.
Text of the packing materials
Accelerated Stability data of the product.
Annexure.
[][]Regulatory Affairs will provide the application, Recipe approval form and product inclusion fee.
[][]PD will generate the Accelerated Stability Data of the product after completion of six month stability
[][]PD will prepare the Annexure after completion of six month accelerated stability.
[][]Annexure for Non Biological drugs will be filled through Annexure I and for Biological drugs will be filled through Annexure II of DA.
[][]Manufacturing License no for Biological and Non Biological License will be checked before filling the corresponding Annexure.
[][]Brand name and blister/bottle/ampoule/vial per pack must be checked before filling the Annexure
[][]Formulation of the product must be filled according to the Stable pilot batch formulation after completion of six month stability.
[][]Compendial reference must be checked for active materials and excipients while filling the Annexure.
[][]Annexure must be filled as Quantity per tablet/capsule for tablet and capsule dosage forms, Quantity per 100 ml for PFS/Syrup/Suspension/ampoules, Quantity per vial for injectable vials.
[][]After completion of Annexure, Manager QA shall check the formulation according to the stable pilot batch formulation and send it to the RA along with other documents.
[][]Regulatory Affairs will arrange for submission and approval of the Annexure from DA.
[][]After approval of the Annexure ,RA will send copies of the Annexure to QA and PD.

Procedure for Sample Sending of INN Products

Required documents for sample sending to the DA are
[][]Application for approval of INN products to director of DA.
[][]Recipe approval form from DA
[][]Fees for analysis
[][]Required quantity of sample of different dosage forms as required by DA
[][]Method of analysis of the active materials as supplied by the manufacturer.
[][]Certificate of Analysis of the active materials.
[][]Working Standard/ Reference Standard of the active materials.
[][]Method of analysis of the finished product
[][]Sample Chromatogram of the active materials.

[][]Regulatory Affairs will arrange for the submission of application, Recipe approval form and fees for analysis to the DA

[][]Quality control will arrange the MOA supplied by the manufacturer, COA and WS and the sample chromatogram after the initial analysis of the sample to be sent to DA.
[][]Manager, QA will check all the documents and arrangement to send to Regulatory Affairs
[][]Regulatory Affairs will arrange the submission to the DA and after the approval will send copies to QA, PD and QC.

Procedure for Annexure amendment

An Annexure can be amended in following cases (not limited to)
[][]Any change in the formulation than the approved Annexure after the process validation.
[][]Inclusion or exclusion of any excipients than the approved Annexure.
[][]Increase or decrease in the quantity of Excipients than the approved Annexure
[][]After any reformulation work.
[][]PD will arrange the justification of Annexure amendment form according to the Annexure – III

[][]In case of inclusion or exclusion of excipients corresponding row will be left blank.
[][]Head of QA and GM plant operation will check the requirements of the justification of Annexure amendment and the formulation and sign for approval.
[][]PD will generate the revised Annexure following step .
[][]Manager, QA will check the revised Annexure according to the revised formulation (pilot batch or validation batch) and documents to RA.
[][]RA will submit and amend the Annexure accordingly and send approved copies to QA.
[][]QA will send revised approved Annexure to PD and SCM and obsolete the previous Annexure.

Annexure:

Annexure – I: Recipe format
Annexure – II: Annexure format
Annexure – III: Format of Annexure amendment form.

correspondence with regulatory affairs Read More »

New Product Development Procedure

New Product Development Purpose:

New Product Development, To detail the standard operating procedure for the manufacturing of new products by Product Development Department.

New Product Development Scope:

This SOP is applicable for new product of  XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]Preformulation: Preformulation is the basic study of the physical and chemical properties of the product prior to start the formulation procedure. Generally, preformulation are conducted to get necessary information to optimize formulation of the products.
[][]Trial Batch: Trial batches are the batches that are conducted in small scale to finalize the formulation of the product in terms of physical feasibility and cost effectively.
[][]Batch: Batches are the Batch that will be prepared to conduct the full physical and chemical stability of the product.
[][]Development Batch: Development batches are the batches that are manufactured and packed using production machinery, for which full physical and chemical accelerated stability will be conducted. The batch size for Development batch should be at a minimum of one tenth of the commercial batch.
[][]Stability Study: Studies conducted to ensure that finished dosage form with excipient will exert to produce its intended effects over the shelf life.
[][]SAF: Sample Advice Form
[][]PB: Pilot Batch
[][]PV: Process Validation
[][]PD: Product Development
[][]DB: Development batch
[][]BMR : Batch manufacturing Record

Responsibilities:

The roles and responsibility are as follows:

Executive/ Sr. Executive PMD

[][]Issue of Product Proposal, Product Brief, Technical Feasibility Analysis Report.

Executive/ Sr. Executive Product Development

[][]Development of new products following this SOP.
[][]Preparation and periodic revision of the SOP
[][]To ensure that the documents technically are accurate and reflects the required working practice

Manager, Supply Chain Management

[][]To ensure availability of all necessary raw materials (active and excipients) for new product purpose

Executive/ Sr. Executive, Quality Control

[][]Analysis of samples of raw materials, trial batches, batches, Development batches, process validation batches.

Manager, Regulatory Affairs

[][]To provide all necessary information on regulatory requirements for new products.

Head of Quality Assurance

[][]Approve the SOP against XX Pharmaceuticals Ltd. master documents and current regulatory requirements.
[][]Ensure effective implementation of the SOP

Procedure:

[][]After getting Product Proposal, Product brief and Feasibility study report from PMD, start information collection about that product from all possible sources; i.e. BP, USP, BNF, Physicians’ Desk Reference (PDR), The Electronic Medicines Compendium, Mark Index, Martindale, Patent manufacturer of the API, Internet etc.
[][]Summarize or highlight that information vital for formulation in the preformulation Study (Annexure-I) & discuss with the members of team through a meeting, if required.
[][]Inform Quality control department to collect sample of the specific product, mention any specific requirement of the product and sample quantity through mail.
[][]Collect the sample of the product from market, preferably from patent manufacturer or of leading Brand Company. Check the physical parameters of the market products to set specifications of our final product.
[][]To get preliminary idea about formulation, make trial of minimum units of each dosage form and record on the Trial Batch (TB) Manufacturing Sheet (Annexure-II). Send the trial batch for QC analysis and figure out best probable formulation.
[][]Based on the information collected in preformulation study and considering trial batch formulation confirm product formula and issue manufacturing instruction for batches (DB). Total manufacturing procedure of batches should be noted properly in to the batch manufacturing record (Annexure – III)
[][] Submit the sample for analysis & compare the results with set specification previously set by the quality control department.
[][]After getting satisfactory results send the batch (DB) sample to production department along with ERP generated packing material requisition for primary packing.
[][] Store the finally packed samples in the accelerated and long term condition according to SOP/PD/003/02 & store the batch manufacturing record in to the product master file. It should be insured that for comparative study, market leading brands, preferably of patent manufacturer is being studied simultaneously.
[][] Analyze and evaluate the stability study results periodically submitted by Quality Control department. Discuss with the head of the department for further proceeding.
[][] After getting satisfactory batch (DB) results, take necessary action for scaling up in to Development batch (PB). Manufacture the Development batch according to the manufacturing formula and instruction of the batch, maintaining all GMP requirements for commercialization of the batch.
[][]Batch size of Development batch should be preferably equivalent to commercial batches and optimization of machine capacity should be considered properly.
[][]Total manufacturing procedure for Development batch should be noted in the Optimization batch manufacturing record (Annexure V), Critical process parameters be justifies and optimized for validation.
[][] For solid oral dosage forms the Development batch size is generally taken to be, at a minimum one tenth that of full commercial batch, or 100000 tablets or capsules whichever is larger, This quantity can be compromised only in case of machine capacity constrain.
[][] Check the analytical results in each & every steps of Development batch. Ensure that the results are within specifications. Then proceed to next step.
[][] Submit the sample of Development batch (PB) to QC laboratory for analysis and stability study following the same procedure as like batch (DB).
[][] To standardize the commercial batch size and to set all the process parameters, first Development batch will be manufactured as optimization batch under the direct supervision of concerned PD Executive. If more than three optimization batches are required for setting all process parameters then it should be justified through risk assessment.
[][] Satisfactory Development batch (PB) result should be informed to all concerned departments to pack as commercial batch according to launching forecast.
[][] Prepare Batch Manufacturing Record (BMR) for a particular product, based on the manufacturing record of Development batches. Finally hand over all related documents of a new product e.g. BMR, Batch formula etc. to Quality Compliance departments for start up the Process validation activities.
[][] On the basis of the approved BMR, next three consecutive commercial batches will be considered as process validation batches.

Reformulation Procedure

[][]A product will be reformulated for any or all of the following causes.
[][]A failure in the evaluation of validation program.
[][]In case of a deviation of a specification that cannot be trouble shoot.
[][]For changing the manufacturing process.
[][]A root cause analysis will be done by the Quality Compliance Department in case of the deviations.

Annexure:

Annexure – I: Preformulation Study Sheet.
Annexure – II: Trial Batch Manufacturing Sheet.
Annexure – III: Batch Manufacturing Record.
Annexure – IV: Optimization batch Manufacturing Record.

New Product Development Procedure Read More »

Certification of Analyst

Certification of Analyst, Purpose :

Certification of Analyst, The purpose of this SOP is to determine the capability of the newly recruited analyst to perform analysis accurately within the specified parameters and to demonstrate the analyst’s ability to perform in quality control laboratory at XX Pharmaceuticals Ltd.

Certification of Analyst, Scope :

This SOP applies to assure that the analysts are familiar with all test parameters, analytical procedures, instruments operation and documentation in quality control laboratory of XX Pharmaceuticals Ltd.

Definitions/Abbreviation:

Standard Operating Procedure (SOP): Standard Operating Procedure.

Responsibilities:

The roles and responsibility is as follows:

Officer/Executive/ Sr. Executive, Quality Control

[][]To follow the instructions of this procedure correctly.
[][]To maintain the records properly as per SOP.

Manager, Quality Control

[][]Responsible for the certification of analyst and verification of results and comparison with acceptance criteria.
[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.

Head of Quality Assurance

[][]Approval of SOP
[][]To ensure the overall implementation of the SOP.

Procedure:

General Precaution(s):

[][]Training should be conducted until the analyst is competent enough to carry out the analysis independently.
[][]Make sure that new employee know about the laboratory safety procedure.
[][]Adequate knowledge on handling of spillages and management of chemicals & reagents in the laboratory.
[][]Hands on waste management in the laboratory.
[][]Understanding the operation, cleaning and calibration procedure of instruments used in the laboratory.

Operation:

[][]Recently approved two specific samples of raw material or finished product or packaging material shall be given to the analyst to perform test for analyst certification.
[][]The samples are to be coded as (A) or (B).
[][]These samples packed in a manner which can prevent exposure to moisture, light and heat.
[][]In-Charge, QC should ensure that the analyst is performing the specified tests following respective method of analysis and specification.
[][]The analytical findings shall be recorded in the respective worksheet and the summary of results shall be entered in the prescribed format (Annexure-I).
[][]In-Charge, QC shall review the results in comparison with the known values for the test carried out and forward to Head of QA for approval.
[][]The analyst shall be considered qualified if the results obtained by him/her within the specification limit and within acceptable limit for certification of analyst.
[][]The details like calculations, chromatograms and spectrums along with comments of Head of QA shall be filed in training file of analyst.
[][]No repeat of the test will be allowed to the analyst.
[][]The result are provided by analyst will be crosscheck to the previous result and check the similarity.
[][]Head of QA will decide for the selection of analyst for routine analysis after review of analysis report. If the analyst is failed to qualify the test analyst will undergo further training.
[][]The certification of analyst shall be applicable to him/her only for carrying out these activities for which he/she is certified.
[][]Re-certification of the analyst shall be carried out once in every three years.
[][]The acceptance criteria for the analytical results shall depend upon the nature of tests carried out and the range provided in the specifications.
[][]Following acceptance criteria may be used for evaluation comparing with approved analyst.
[][]Assay by Spectrophotometer +/- 1% of previous value
[][]Assay by HPLC +/-0.5% of previous value
[][]IR spectra should match with standard and previous spectra
[][]Water content by KF +/-1% of previous value

Annexure:

Annexure-I: Analyst Certification Report.

Certification of Analyst Read More »

Dissolution Tester Calibration with Operation and Cleaning

Dissolution Tester Calibration, Purpose :

Dissolution Tester Calibration, The purpose of this SOP is to describe the operation, calibration and cleaning of Dissolution Tester (Model: Electrolab, EDT 14Lx).

Dissolution Tester Calibration, Scope :

This procedure is applicable for Dissolution Tester (Model: Electrolab, EDT 14Lx), installed in the quality control laboratory at XX Pharmaceuticals Limited.

Definitions/Abbreviation:

[][]SOP: Standard Operating Procedure
[][]QC: Quality Control
[][]Dissolution test: Dissolution test is a means to monitor the rate of release of a drug substance from a dosage form to ensure consistency of manufacture and compliance with release specifications.
[][]RPM: Rotations per minute
[][]LED: Light emitting diode
[][]Concentricity: The quality of having the same center (as circles inside one another).
[][]Wobble: Move sideways or in an unsteady way.
[][]NMT: Not more than.

Responsibilities:

The roles and responsibility is as follows:

Officer/Executive/ Sr. Executive, Quality Control

[][]To ensure that the instructions of this procedure are correctly followed.
[][]To ensure cleaning of dissolution tester maintaining safety rules.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.
[][]Schedule calibration of the instrument at the defined intervals.

Head of Quality Assurance

Approval of the SOP
To ensure the overall implementation of the SOP.

Procedure:

General precautions or operational safety:

[][]Do not start the heater if there is no water in the tank.
[][]Always maintain the liquid level within the tank above the minimum level mark using purified water only.
[][]Disconnect the power supply before moving, emptying or cleaning of bath.
[][]Spillage must be cleaned up immediately after use.
[][]Do not use any aggressive material or strong solvent to clean the jar and water bath.
[][]Locate the system on a level bench without movement or distortion.
[][]Do not hold the stirrer while in operation.
[][]For lifting up the stirrer, make sure the paddles are stop.
[][]Do not disturb the sensor tube while cleaning the tank.
[][]External probe should be handled with care.
[][]Use sinkers if the dosage form unit floats. Close the vessels with the cover during Operation.

System Operation:

[][]After the System is set up, switch on the power.
[][]After Power On, the Instrument will initialize itself; the logo screen will flash for 3 seconds and then idle screen will be displayed.
[][]The idle screen displays the current status of the instrument indicating the Date, Time, RPM, Bath Temperature, External probe and loaded protocol number.
[][]Press F3 Key to login.
[][]Username and Password needs to be added.
[][]Press F1 key to enter the username & password or F3 Key to go back to the previous screen.
[][]The idle screen will be displayed.
[][]If security is disabled then the adjacent idle screen will be displayed.

ELECTROLAB
EDT 14Lx
DISSOLUTION
TEST APPARATUS

[][]Press F1 or F2 Key from front panel to enter MENU or PREPARE
[][]Menu Press F1 Key from front Panel to enter menu screen.
[][]Menu <Configure>
[][]Press 1 from alphanumeric keypad to enter configuration menu.
[][]If F3 key is pressed the previous screen will be displayed.
[][]Menu <Configure> l sampling l
[][]Press 1 from alphanumeric keypad to enter sampling menu.
[][]Menu <Configure>l sampling l [ Manual] [][]Press 1 to select manual sampling though syringe manifold or 2 to select manual sampling though pipette.
[][]Menu <Configure>l Individual Probe l
[][]Press 2 to enter individual probe screen. Press 1 from alphanumeric keypad to select the individual probes. The number of probes can be selected either to 6/8/12/14 using up or Down arrow key, press enter to save the No. of probes and return back to configure screen.
[][]Press 2 to select option number.
[][]Press F3 key to return back to the Configure screen.
[][]Menu <Configure>l Temp Gradient l
[][]Press 3 to enter temp gradient.
[][]Set Temp gradient up to 1.5° C using increment & decrement key.
[][]Temperature Controller set.

F1 key: To ‘ON’ the temp Controller.
F2 key: To ‘OFF’ the temp Controller.
F3 key: To ‘SAVE’ & to return back to the Configure screen.

[][]Menu <Configure>l communication l
[][]Press 4 from front panel to enter Communication.
[][]Select RS232 for printer/PC and ETHERNET for LAN connection using 1 or 2 numeric keys.
[][]Press F3 key to go back to configure screen.
[][]Menu <Configure>l Stirrer l
[][]Press 5 in configure screen.
[][]Press 1 to ON the Stirrer and press 2 to OFF the stirrer.
[][]Menu <Configure>l Auto Disp. l
[][]Press 7 to enter auto dispenser screen.
[][]Press 1 or 2 numeric keypad to activate auto dispenser.
[][]Menu <Configure>l Instur. No. l
[][]Press 8 to enter instrument number.10 alphanumeric character serial numbers can be entered.
[][]Press F1 keys to save the entered serial number and F3 to go back to previous screen.
[][]Menu <Protocol>
[][]Press 2 to enter protocol menu.
[][]Menu< Protocol >l Load Protocol l
[][]Press 1 to enter Load Protocol.
[][]20 Programmable protocols can be loaded
[][]Protocol No- Can be loaded using UP/Down key & to register the No. Enter key needs to be pressed.
[][]Press F1 to load next protocol and Press F2 to load previous protocol.
[][]Press F3 to go back to the protocol screen.
[][]Menu< Protocol >l Edit Protocol l
[][]Press 2 to enter Edit Protocol.

[][]Select the protocol which needs to be editing using Up/down arrow and press ‘enter’ key.
[][]The respective protocol details such as Drug name, Media name, pH value, Temperature, Media volume , Power fail, Apparatus, Time Table, Sampling Info, details need to be entered.
[][]The protocol details can be edited using alphanumeric keypad.
[][]The next parameters can be selected for editing before saving the previous parameter by pressing F3 key from front panel.
[][]To select different apparatus press enter key and select the desired apparatus using numeric keys.
[][]To edit time table parameters press Enter key. The sampling time interval, action and total number of samples (1 to 24) can be set as per user requirement using shift & alphanumeric keys.
[][]For the single time point, action table will have only one sampling option. Infinity (min) can be selected after last sample.
[][]For the multiple time point, action table will have only two sampling options media change and sample. Infinity (min) can be selected after last sample.
[][]Press F3 to save & go back to main menu screen.
[][]Menu <Settings >
[][]Press 3 to enter settings
[][]Menu <Settings > l Clock l
[][]Press 1 alphanumeric keypad to enter Clock setting screen
[][]Set Date and Time using ▲▼◄► arrow keys
[][]Press F1 from front panel to save the entered date and time, the idle screen will be displayed
[][]Press F1 from front panel to go back to the setting screen.

[][]Menu <Settings > l Wake Up l
[][]In this parameter the sleep mode time and date are set. The instrument will start automatically at the set time and date for attaining the bath temperature.
[][]Press 2 from setting screen to enter the wakeup setting screen.
[][]Wake up time and date needs to be added using Up/Down and Side arrow keys.
[][]Press F1 key to turn ON the wake up parameter, the LCD display light will be turn OFF automatically and idle screen will be displayed. Or press the F2 key to OFF the wakeup alarm.
[][]Menu <Jar Tamp >
[][]Press 6 from main menu screen to observe the jar tamp attained by individual jar.

To set RPM

[][]Press RPM key from front panel.
[][]Press numeric key to register the RPM range from 20 to 300 RPM.
[][]Press F1 key to Turn-on the motor & F2 key to Turn off.
[][]If RPM is out of range an error screen will be displayed.
[][]To Set Temperature
[][]Press Temperature key from front panel.
[][]Press numeric key to register the temperature range from 200 C to 400 C.
[][]Press F1 to turn On & F3 to turn off heater.
[][]If temperature is out of range an error screen will flash for 3 seconds.
[][]To prepare the test
[][]Load the appropriate protocol no. & press F2 key to start preparing the test.
[][]Batch No. & A.R. No. will be displayed. Using down arrow and enter key, add the batch No. & A.R No. (Lab. Control No.) up to ten digits. Press enter key to register the number.

[][]It will display checking connection where the instrument establishes link with the syringe/peristaltic pump and sample/fraction collector.
[][]After the connection between the instruments is done, sample collector will initialize & ‘Lift Not Park’ Indication will be display (If lift is not parked).
[][]‘Wait for the temperature’ indication will be display till the set temperature is achieved. User can also access MENU to cheek jar temperature.
[][]Ready indication will glow on front panel when jar temperature reach to set point & start indication will be displayed.
[][]Press START key form front panel to start the test.
[][]‘Drop the tablet and press START’ message will be displayed immediately if paddle or 45 was selected and if basket or paddle over disk was selected then ‘Press lift up, Load Apparatus’ will be displayed on screen.
[][]Press Enter to start the test, run screen will be displayed. Current status of the test and sample timing are displayed throughout the test.
[][]After completion of work, switch ‘OFF’ the instrument.
[][]Switch ‘OFF’ the mains when not required.
[][]Fill up the operation log book for Dissolution tester as per Annexure-III.

Physical Calibration

[][]Frequency: Perform mechanical calibration of the dissolution tester once in every six months or if the system has been moved, serviced or a malfunction is suspected.

Temperature Calibration:

[][]Switch on the mains.
[][]Set the temperature to 37°C by following the temperature setting procedure given in operation.

[][]Ensure that the jars are filled with water.
[][]Allow the instrument to stabilize.
[][]Measure the temperature of the water bath and of each jar with a calibrated thermometer and compare the result against the digital display on the apparatus.
[][]Record the observation as per Annexure-I.
[][]Acceptance Criteria: 37°C ± 0.5°C.

RPM Calibration:

[][]Switch on the mains.
[][]Set the RPM to 50 as per procedure given in the operation.
[][]Start the stirrer and measure the RPM by using calibrated tachometer.
[][]Record the observation as per Annexure-I.
[][]Similarly check the RPM 75, 100, and 150 and record the observations.
[][]Acceptable criteria: ± 4% of set value.

Time Calibration:

[][]Switch on the mains.
[][]Set the desired time (30 and 45 minutes) by following the temperature setting procedure given in operation.
[][]Check the time using a calibrated stop watch and record the observations as per Annexure-I.
[][]Acceptable criteria: ± 2% of set value.

Chemical Calibration (Performance Verification Testing)

[][]Frequency: Perform chemical calibration of the dissolution tester once in a year or if the system has been moved, serviced or a malfunction is suspected.
[][]For USP Dissolution Apparatus 1 (basket) and Apparatus 2 (paddle):
[][]If the instrument is outside calibration, a label of “Out of calibration” is placed.
[][]Apparatus must be calibrated with the following :
[][]Disintegrating Type – USP Prednisone Tablets 10 mg at 50 rpm
[][]Non-disintegrating Type – USP Salicylic Acid Tablets 300 mg at 100 rpm
[][]Checking Standards in the on line-USP and printing Lot-Specific Standard Certificates. Verifies Standard Lots are current within expiry.

Disintegrating Type – USP Prednisone tablets 10 mg at 50 rpm:

[][]Follow the directions for storage and use on the label of the reference standard.
[][]If drying instructions are included on the label, only dry sufficient quantity required for the test (use a clean, dry vessel when drying and not the original container).
[][]Standard solutions must be prepared on the day of use.

Prednisone standard preparation:

[][]Accurately weigh 20 mg Prednisone standard into a 100 ml volumetric flask containing 5 ml methanol.
[][]Sonicate to dissolve and dilute to volume with distilled or purified water and mix well.
[][]Further dilute 5.0 ml of this solution to 100 ml with distilled or purified water and mix well.
[][]Dissolution medium preparation and de-aeration:
[][]Filter the dissolution medium (Distilled or purified water 500 ml) with the aid of a vacuum through a 0.45 µm-porosity membrane filter into a suitable filtering flask.

Test procedure:

[][]Using a volumetric flask, measure 500 ml distilled or purified water into each of the six vessels.
[][]Allow medium to equilibrate for approximately 30 minutes before test is commenced.
[][]When dissolution bath has equilibrated, check the temperature of each vessel is 37.0°C ± 0.5°C.

[][]Carefully weigh 6 de-dusted USP Prednisone Tablets 10 mg.
[][]Drop one previously de-dusted tablet into each of the vessels via the sample holes in the lids, raising the stirrer shaft fully before dropping the tablet into the vessel, and pushing the shaft fully down when the tablet has reached the bottom.
[][]Operate the apparatus at 50 rpm for 30 minutes.
[][]After 30 minutes withdraw approximately 50 ml midway between the surface of the dissolution medium and the top of the blade, not less than 1cm from the vessel wall.
[][]Filter through a Whatman Number 1 filter paper, discarding the first few ml of filtrate.
[][]Scan the standard from 300-200 nm to obtain the maximum absorbance at the optimum wavelength (approximately 242 nm).
[][]Determine the absorbance of the six samples at that wavelength in fixed mode.
Calculate the percentage prednisone dissolved for all 12 stations using the following calculations:

% Dissolved =
Absorbance of Sample x Standard Concentration (mg/l) x Standard Potency x 100 DIVIDED BY
Absorbance of Standard x Sample Concentration if 100% dissolved (C100)

Acceptance Criteria:

[][]Check the percentage released limit of USP dissolution calibration tablets (Disintegration type: Prednisone tablets) from the respective batch certificate provided by USP.
[][]If any one station is outside of specification, place an “Instrument out of calibration, DO NOT USE” label on the instrument.
[][]Inform In-charge, QC; if the results do not meet the criteria.

Test interpretation:

The apparatus shall be suitable if the individual calculated values at each indicated speed are within the range specified in the tablet obtained with the each lot of tablets.

Note: An amount of alcohol not to exceed 5% of the total volume of the standard solution may be used to bring the prednisone standard into solution prior to dilution with dissolution medium.

Recording of Results:

[][]All relevant information on the calibration must be completed on Annexure-II.
[][]When all the results have been checked affix a Calibration label to the instrument.

Cleaning procedure

[][]Lift the stirrer unit by using “lift UP” key.
[][]Immerse the replenishment tubes in a vessel of the instrument or a beaker outside of the instrument containing purified water.
[][]Press F1 Key [Menu] from front panel.
[][]Press 5 from alphanumeric keypad to enter Run.
[][]Again press 2 for cleaning cycle.
[][]Iterations of cleaning cycle will be displayed, press F3 to save the command.
[][]Batch No.:, A. R. No.:, User Name: will be displayed. Press Enter 3 times.
[][]Display will be showed Press UP to edit/Press Enter to proceed, again press Enter.
[][]It will display checking connection where the instrument establishes link with the syringe/peristaltic pump and sample/fraction collector. At that time wait for few seconds.
[][]Press START
[][]ABORT STOP will be displayed on the LED screen.
[][]To start the cleaning cycle, press Start.
[][]After completion of cleaning cycle display will show checking connection Press START
[][]ABORT STOP
[][]Press F3 to stop the cleaning cycle and start the empty tube cleaning.
[][]Before start the empty tube cleaning, the replenishment tube should be placed in the open air from vessel or beaker.

[][]Remove the test vessels from their place and discard the medium.
[][]Wash each vessel with purified water and then set them inside the dissolution bath number wise.
[][]Remove basket/ paddle apparatus from the dissolution tester. Wash them with purified water and dry with tissue paper and keep at dedicated place.
[][]Clean and replace the water from dissolution bath fortnightly (once in every two weeks) or if necessary.
[][]Remove all vessels from the dissolution bath.
[][]Remove the basket/ paddle apparatus from the stirrer unit.
[][]Remove the circulating pipe which is provided at the right rare side of the dissolution bath.
[][]Start the circulation pump from the option menu and drain the dirty water in a waste water bucket.
[][]Insert the circulating pump in its proper place.
[][]Wash the dissolution bath with raw water, detergent solution and then again with raw water sequentially until no foam of detergent remains in the bath.
[][]Wash the bath finally with purified water and fill the bath with the same up to the level mark.
[][]De-dust the outer surface of the instrument with a clean dry cloth every day.

Annexure: Dissolution Tester Calibration

Annexure-I: Physical Calibration Information Sheet for Dissolution Tester
Annexure-II: Chemical Calibration Information Sheet for Dissolution Tester
Annexure-III: Operation Log book for Dissolution Tester

Dissolution Tester Calibration with Operation and Cleaning Read More »

Water Sampling and Analysis in QC Laboratory

Water Sampling, Purpose :

Water Sampling, The purpose of this SOP is to describe the procedure for sampling and analysis of water in quality control laboratory.

Water Sampling, Scope :

This procedure is applicable for sampling and analysis in Quality Control Laboratory for purified water, water for injection, purified steam condensate, potable water, drinking water and effluent treatment plant water from different user points used in XX  Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]QC: Quality Control
[][]QA: Quality Assurance
[][]QCom: Quality Compliance
[][]COA: Certificate of Analysis
[][]WFI : Water for Injection
[][]PW: Purified water
[][]ETP: Effluent treatment plant

Responsibilities:

The roles and responsibility is as follows:

Lab Attendant, QC

[][]To collect water sample from different sampling points.

Officer / Executive, QC Officer / Executive, QC

[][]To prepare schedule sampling of water.
[][]To organize the sampling of water.
[][]Analysis of water and preparation of respective test report.
[][]Trend analysis of water.
[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Sr. Executive, QC

[][]Reviewing of test report.

Manager, Quality Control

[][]Approval of test report.
[][]To ensure implementation of the SOP after training.

Head of Quality Assurance

[][]To ensure the overall implementation of the SOP.
[][]Approval of the SOP.

Procedure:

Precaution(s):

[][]Use gloves, mask & cap during sampling.
[][]Collect sample carefully to avoid contamination.
[][]Carefully collect water sample with high temperature and close the cap of container freely.

Sample Collection :

[][]Take required number of 500 ml to 1 Liter clean glass containers with cap for sampling.
[][]Open sampling points such as tap fixtures / hosepipe and allow water to run for not less than 1 minute.
[][]Rinse the container with respective water.
[][]Collect approximately 500 ml of water and immediately recap the sample containers after collecting samples. Keep the cap slightly loose when water temperature is above 30°C.
[][]Label the sample container providing information such as name of water, sample point no. / location, time, initial of sampler and date of sampling.
[][]Transfer the sample immediately to laboratory and analyze the sample within 24 hours of sampling. Preserve the sample in refrigerator (2°C to 8°C), if required.
[][]Entry information of sampling in sampling register after sampling.

Test Schedule :

Perform the test as per the following schedule :

Source of Water /Test frequency

Potable Water/ Once in a month
Purified Water/ Once in 14 days
ETP Water /Once in a week
Water for Injection/ Once in a week

Chemical Analysis :

[][]Perform analysis of water as per respective specification and method.
[][]Compile the raw data and prepare the certificate of analysis as per respective annexure with the test results & take approval of the COA.
[][]Share the water test reports with Engineering department and or Production department.
[][]Water test results are to be evaluated on a continuous basis and should be summarized in trend analysis report six monthly in order to identify significant trends.
[][]Inform respective department i.e. Engineering, Production and Quality Assurance Department whenever atypical data found beyond alert limit.
[][]Inform respective department i.e. Engineering, Production and Quality Assurance Department for taking actions whenever data found beyond action limit.

Annexure:

Annexure-I : Format for Certificate of Analysis for Potable water/Drinking water
Annexure-II : Format for Certificate of Analysis for Purified water/Water for injection/Purified Steam Condensate
Annexure-III : Format for Certificate of Analysis for Effluent Water
Annexure-IV : Format for Water Sampling Register
Annexure-V : Water sampling points

Water Sampling and Analysis in QC Laboratory Read More »

Calibration of Semi-micro Osmometer with operation & cleaning

Calibration of Semi-micro Osmometer, Purpose:

Calibration of Semi-micro Osmometer, The purpose of this SOP is to describe the operation, calibration and cleaning of Semi-micro Osmometer (Brand: KNAUER; Model: K-7400) used in the quality control laboratory of XX Pharmaceuticals Limited.

Calibration of Semi-micro Osmometer,Scope:

This procedure is applicable for Semi-micro Osmometer, installed in the quality control laboratory general block of Labaid Pharmaceuticals Limited.

Definitions / Abbreviation:

Standard Operating Procedure (SOP): Standard Operating Procedure.
QC: Quality Control.

Responsibilities:

The roles and responsibility is as follows:

Sr. Executive/Executive, QC

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.
[][]Schedule calibration of the instrument at the defined intervals.

Head of Quality Assurance

Approval of the SOP.
To ensure the overall implementation of the SOP.

Procedure:

Precaution(s):

[][]Prior to use, user must ensure that equipment is calibrated.
[][]To ensure a fixed sample volume, always introduce the solutions with a clean and dry pipette into the measuring vessel.
[][]Handle the thermistor always very carefully. All abrasive materials should be kept away from it.
[][]Solutions containing proteins, such as sera, can only be measured once. Freezing causes denaturisation of the protein so that repetition of the measurement with the same sample would result in increased values. Thus, in the case of sera, only one measurement is possible for one sample.
[][]Only real osmolalities can be measured. It is not possible to prepare other standard solutions by dilution of a calibration solution since the activity coefficient of the solution changes with dilution.
[][]In this case Store the water which is used for the zero point calibration in glass bottles.
[][]If the same salt solution is measured several times, it must be mixed after thawing (stir briefly). During the thawing process ice floats to the top of the solution. As ice does not contain salt, the top layer of the solution is diluted while thawing.
[][]Calibration solutions can become more concentrated if the bottle is opened frequently. So, use KNAUER calibration solutions in glass ampoules.
[][]Prior to the measuring, a little bit water condensed in the cooling compartment should be removed with a dry cloth.

Operation:

[][]Preparing the Osmometer K-7400
[][]Switch ON the instrument at least 5 minutes before use.
[][]Press the vibrator key to check the stirrer. It will run for a second.
[][]Optionally a thermo printer can be connected to the RS232 socket. The result of each measurement will be printed automatically.
[][]After a calibration, an outprint of Calibration will be found automatically.
[][]In case of interrupted runs (caused by any error), the screen displays the corresponding error message.

Preparing a Measurement

[][]Place 0.15 ml sample or calibration solution into a clean, dry measurement vial.
[][]Put the vial all the way into the adapter. The meniscus of the liquid must be horizontal.
[][]Place the measuring head on the instrument in such a way that the vial extends into the cooling cavity.
[][]Thus the instrument is ready for calibrating or measuring.

Calibration:

[][]Prepare the instrument for a measurement of deionised water.
[][]Set the first field in the second row of the CALIBRATE screen to „0000“.
[][]Press the start key.
[][]After finishing the run on the screen is displayed 0000 mOsmol > -0.81°C<.
[][]To accept this value, press the START key again.
[][]Wait for the warming up to the stand-by temperature.
[][]Prepare the instrument for a measurement of a 300 mOsm/kg calibration solution.
[][]Activate the second calibration field and select “0300” and repeat steps
[][]For a 4 point calibration, repeat the procedure for calibration fields

Measuring Samples:

[][]Prepare the instrument for a measurement of a sample solution.
[][]Press the START key to start the measurement run.
[][]The instrument detects the freezing point depression and if the crystallisation occurred properly displays the corresponding osmolality on the main screen.
[][]The printer output is given automatically.
[][]If no crystallisation (temperature increase) takes place after the automatically start of the vibrator the measurement will be stopped with the error message “> ERROR < NO FREEZE”.
[][]If the crystallisation (temperature increase) takes place before the start of the vibrator the measurement also will be stopped with an error message> ERROR < FREEZE.
[][]Do not remove the measurement vessel from the adapter before the sample is molten. Otherwise the danger of damaging the measuring head is given. The sample melting can be accelerated by warming up with the fingers.

Cleaning procedure:

[][]Measuring vessel and thermistor should be cleaned occasionally with KNAUER cleaning solution supplied with the instrument. (Dilution: 1: 10 solution in purified water of 40±5°C)
[][]Clean and dry the measuring vessels with alcohol or acetone because remaining solvent vapours could cause false results.

Annexure:

Annexure-I: Operation Logbook for Semi-micro Osmometer.

Calibration of Semi-micro Osmometer with operation & cleaning Read More »

Calibration of HPLC System With Operation & Cleaning

Calibration of HPLC, Purpose:

Calibration of HPLC, The purpose of this SOP is to describe the operation, calibration and cleaning of High Performance Liquid Chromatography system with DAD & RID (Brand: Agilent; Model: 1260 Infinity) used in the quality control laboratory at XX Pharmaceuticals Limited.

Calibration of HPLC, Scope:

This procedure is applicable for Agilent PC based Quaternary Gradient Automated High Performance Liquid Chromatography System, installed in the quality control laboratory of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]SOP : Standard Operating Procedure.
[][]QC : Quality Control.
[][]HPLC : High performance liquid chromatography
[][]DAD : Diode Array Detector
[][]RID : Refractive Index Detector

Responsibilities:

The roles and responsibility is as follows:

Sr. Executive/Executive, QC

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.
[][]Schedule calibration of the instrument at the defined intervals.

Procedure:

General Precaution(s):

[][]Prior to use, user must ensure that instrument is calibrated.
[][]Be sure that the drain valve is open before purging and tightly closed after purging.
[][]Before shutting down the system ensure that column is thoroughly washed and kept in appropriate solvent.
[][]Mobile phase, Diluting solvents and other solutions, which are used in HPLC, should be freshly prepared.
[][]Degas the mobile phase before using.
[][]Rinse the flow lines after completion of analysis as per solvent used in the system.
[][]Make sure that the solvent filter/diffuser is completely immersed in solvent.
[][]Update the solvent bottle before run.
[][]During set up the flow rate at priming, do not press Run/Stop to start the pump.
[][]Purge the pump with fresh diluent (filtered and degassed).
[][]Clean the solvent diffuser/filter once in a week.
[][]Fill up & attach Labels of the solvent reservoirs properly.

Operation of DAD:

[][]Switch ‘ON’ the power of Quaternary Pump, Autosampler, Thermostatic Column Compartment, Detector, CPU, Monitor if already not switched on.
[][]Wait until all the modules are initialized and are ready for next operation.
[][]Set specified column in the column compartment.
[][]Computer and Software Log in
[][]Double click on the icon of HPLC_DAD (online) from Desktop.
[][]Click Download to instrument/Upload from instrument/New method from instrument.

Purging Lines

[][]Insert the solvent tubing into the appropriate reservoirs.
[][]Gently shake the filters in the reservoirs to remove any bubbles that may be trapped.
[][]Open the purge valve of pump by half (1/2) turning anticlockwise.

[][]Go to the Agilent modular controller screen.
[][]Click Switch On to switch on all the modules.
[][]Right Click on the mouse over Quat. Pump module.
[][]Click Method.
[][]Enter flow rate 5.00 ml/min.
[][]Enter the % of composition of the desired purging line.
[][]Press OK/Apply.

Update the Solvent Bottle

[][]Right Click on the mouse over Quat. Pump module.
[][]Click Bottle Fillings.
[][]Enter the Solvent Volume of respective Bottles and enter the Total volume of the Bottle.
[][]Click OK.

[][]Create a new Method
[][]Click Method from menu.
[][]Click New Method.
[][]Click Method from menu.
[][]Click Entire Method…
[][]Click OK > OK >OK.
[][]Select Quart. Pump.
[][]Enter Flow rate, % of solvent ratio, stop time and maximum pressure Limit (Max. 400).
[][]For Gradient flow enter the time program.
[][]Select Sampler.

[][]Click OK.
[][]Click desire method.
[][]Click Add Method.
[][]Click OK>OK> OK>OK> OK.
[][]Click Method from menu.
[][]Click Save Method As…
[][]Select location and enter Method Name.
[][]Click OK.

Create a new Sequence

[][]Click Sequence from menu.
[][]Click New Sequence Template.
[][]Click Sequence from menu.
[][]Click Sequence Table…
[][]Enter Sample Location, Sample Name, Method Name and Data File.
[][]Click OK.
[][]Click Sequence from menu.

[][]Click Sequence Parameters…
[][]Locate the Data File Path.
[][]Click Post-Sequence Command/macro.
[][]Select STANDBY from dropdown list.
[][]Click OK.
[][]Click Sequence from menu.
[][]Click Save Sequence Template As…
[][]Select location and enter Sequence Name.
[][]Click OK

Run Samples

[][]Select the created Method.
[][]Select the created Sequence.
[][]Insert the solvent tubing into the appropriate reservoirs.
[][]Click Switch On to switch on all the modules.
[][]Wait for Base line stable.
[][]After getting the Baseline stability click RunControl from menu.
[][]Click Run Sequence.
[][]Instrument will be run as per selected Method and Sequence; and data will save as per selected location.

Data Processing

[][]Double click on the icon of HPLC DAD (offline) from Desktop.
[][]Select desire Sequence file from Data Analysis window.
[][]Double click a file of Navigation Table.
[][]Click Graphics form Menu.
[][]Click Signal Options.
[][]Click Compound Names.
[][]Click OK.
[][]Click Edit or Set Integration Events Table.
[][]Remove the unexpected peak either using Area or Height rejection or using time integration event program.
[][]Click OK.
[][]Click Calibration from Menu.
[][]Click Calibration Settings
[][]Enter Amount Units.
[][]Click OK.
[][]Click Calibration from Menu.
[][]Click New Calibration Table…
[][]Enter Default Amount (Standard wt. in mg).
[][]Click OK.
[][]Enter Compound Name in Calibration Table.
[][]Click OK.
[][]Click Method from Menu.
[][]Click Save Method As Save As New Master Method.
[][]Select location and enter Method Name.
[][]Click OK.
[][]Click Sequence from menu.
[][]Click Sequence Table
[][]Select the desire processing Method and Fill down.
[][]Select Sample Type as Calibration using drop down list for standard injections.
[][]For first Standard select Replace both for Update RF & Update RT using drop down list.
[][]Enter Multiplier.
[][]Click Reprocess.
[][]Click OK.
[][]Sequence will be processed as per selected processing method.

Report Print

[][]Select Data/Set of Data.
[][]Select Review.
[][]Click File from Menu.
[][]Clock Load Template.
[][]Select Template.
[][]Click Open.
[][]Click Print Report from Menu.

Operation of RID:

[][]Switch ‘ON’ the power of Quaternary Pump, Autosampler, Thermostatic Column Compartment, Detectors, CPU, Monitor if already not switched on.
[][]Wait until all the modules are initialized and are ready for next operation.
[][]Set specified column in the column compartment.
[][]Computer and Software Log in
[][]Double click on the icon of HPLC_RID (online) from Desktop.
[][]Click Download to instrument/Upload from instrument/New method from instrument.

Purging Lines

[][]Flow the operation steps
[][]Update the Solvent Bottle
[][]Flow the operation steps

Stabilization of RID detector

[][]Insert the solvent tubing into the appropriate reservoirs. Be sure that the detector waste lines and the sample loop waste line drain into the appropriate container.
[][]Right Click on RID window.
[][]Click Open Purge Valve.
[][]Right Click on RID window.
[][]Click Switch Recycling On.
[][]Wait for baseline stability.
[][]After baseline stability right Click on RID window.
[][]Click Close Purge Valve.
[][]Right Click on RID window.
[][]Click Switch Recycling Off.

Create a new Method

[][]Flow the operation steps
[][]Select DAD.
[][]Deselect Signals and UV Lamp if they are not previously deselected.
[][]Click OK.
[][]Click RID.
[][]Enter the Optical Input Temperature.
[][]Click OK.
[][]Select RID1 A, Refractive Index Signal.
[][]Click Add Method.
[][]Flow the operation steps

Create a new Sequence

[][]Flow the operation steps
[][]Run Samples
[][]Flow the operation steps
[][]Data Processing
[][]Double click on the icon of HPLC_RID (offline) from Desktop.
[][]Flow the operation steps
[][]Click File from menu.
[][]Click Load Signals…
[][]Select a standard file.
[][]Select RID1 A, Refractive Index Signal.
[][]Click OK.
[][]Flow the operation steps

Report Print

Flow the operation steps

Shut Down

[][]Click “Off” icon to stop Instrument.
[][]Carryout system suitability test every day before analysis.
[][]Fill up the column information logbook after analysis.
[][]Wash the column following as per HPLC Column Washing Procedure
[][]Exit from the “OpenLab Chemstation’’ software.
[][]Put off the power of equipment and computer.
[][]Record in the Logbook for operation of HPLC (as per Annexure-IV).

Operation of Queue Planner:

[][]When two or more sequence to be run with the same column and same mobile phase/mobile phase composition; Queue Planner is required.
[][]Save individual method and sequence for individual operation.
[][]Click RunControl from menu.
[][]Click Queue Planner.
[][]Insert/Append sequence when required. Use Up/Down button to rearrange the sequence.
[][]Click Save As.

[][]Select location and enter file name.
[][]Click Add to back of queue.
[][]During using of Queue Planner keep wash method and STANDBY at the last sequence only.

Calibration of HPLC:

Calibrate the HPLC at every 6 month’s frequency either by following procedure or as per supplier’s protocol:
[][]Quaternary Pump : 1260 Qart Pump VL
[][]Check the LED is on.
[][]Turn on the power.
[][]Set Flow Rate at 0.500 ml/min and 5.000 ml/min.
[][]Check flow rate, average value, STD, accuracy and precision.
[][]Record the value in Calibration Information Sheet for Pump Flow and Accuracy of Quaternary Pump VL (Annexure-I).
Set the following parameters:
Injection Volume : 0.0 µl
Flow Rate : 2.0 ml/min
Wavelength : 265 nm
Run Time : 26.0 min
Column Temperature : 40.0 °C
Evaluated Compound : Acetone
[][]Set the following Gradient Program and record the data:
Gradient Pump A/ Pump B
Initial 00% /100%
Step 1 20% /80%
Step 2 40% /60%
Step 3 60% /40%
Step 4 80%/ 20%
[][]Check the height, noise, drift and composition for various compositions.
[][]Record the Height, Noise, Drift and Composition in Calibration Information Sheet for Gradient Composition (Annexure-I).
[][]Thermostatic Column Compartment: 1260 TCC
[][]Check the LED is on.
[][]Turn on the power.
[][]Set Flow Rate 1.0 ml/min.
[][]Set column temperatures at 80.0°C and 40.0°C.
[][]Check the Column Temperature Accuracy and Column Temperature Stability from Column Compartment Display in 4 munities interval.
[][]Record the value in Calibration Information Sheet for Thermostatic Column Compartment (Annexure-II).

[][]Variable Wavelength Detector: 1260 DAD VL
[][]Check the LED is on.
[][]Turn on the power.

Set the following parameters:
Pump Flow Rate : 1.0 ml/min
Run Time : 2.0 min
Injection volume : 15 µl
Column Temperature : 40.0°C
Sample : Caffeine Std
Evaluated Compound : Caffeine
[][]Evaluating Standard Concentration : 25.0 µl/ml (form Certificate of Analysis)
[][]Set wavelengths at 205 nm, 245 nm and 273 nm.
[][]Check the area of the chromatograms for respective wavelengths.
[][]Record the value in Calibration Information Sheet for Variable Wavelength Detector (Annexure-III).
[][]Set the following parameters:
Flow Rate : 1.0 ml/min
Run Time : 24.0 min
Noise Evaluation Start Time : 3.0 min
Noise Evaluation Duration : 20.0 min
Injection Volume : 0.0 µl
Column Temperature : 40.0°C
[][]Check the Noise and Drift.
[][]Record the Noise and Drift in Calibration Information Sheet for Noise and Drift of Variable Wavelength Detector (Annexure-III).
Set the following parameters:
Flow Rate : 1.0 ml/min
Column Temperature : 40.0°C
Run Time : 7.0 min
Injection Volume : 10.0 µl
Noise Evaluation Start Time/Duration : 3.00 min/3.00 min
Evaluation Standard Concentration : 25 µg/ml (Certificate of Analysis)
Sample : Caffeine Std
Evaluation Compound : Caffeine
Detector Path Length : 10 mm
Wavelength : 273 nm
[][]Check the signal to noise ratio.
[][]Record the Signal to Noise in Calibration Information Sheet for Signal to Noise of Variable Wavelength Detector (Annexure-III).
Set the following parameters:
Flow Rate : 1.0 ml/min
Column Temperature : 40.0°C
Run Time : 2.0 min
Injection Volume : 20.0 µl

Sample : Caffeine Std
Wavelength : 273 nm
Evaluation Compound : Caffeine
[][]Check the area and height and find the R/F, R/F average, R/F STD and Coefficient of Determination.
[][]Record the linearity in Calibration Information Sheet for Response Linearity of Variable Wavelength Detector (Annexure-III).
[][]Refractive Index Detector: 1260 RID
[][]Check the LED is on.
[][]Turn on the power.
Set the following parameters:
Flow Rate : 1.0 ml/min
Run Time : 24.0 min
Noise Evaluation Start Time : 3.0 min
Noise Evaluation Duration : 20.0 min
Injection Volume : 0.0 µl
Column Temperature : 40.0°C
[][]Check the Noise and Drift.
[][]Record the Noise and Drift in Calibration Information Sheet for Noise and Drift of Refractive Index Detector (Annexure-IV).
Set the following parameters:
Flow Rate : 1.0 ml/min
Column Temperature : 40.0°C
Run Time : 7.0 min
Injection Volume : 10.0 µl
Noise Evaluation Start Time/Duration : 3.00 min/3.00 min
Evaluation Standard Concentration : 25 µg/ml (Certificate of Analysis)
Sample : RID Std kit
Evaluation Compound : Glycerin
Detector Path Length : 10 mm

[][]Check the signal to noise ratio.
[][]Record the Signal to Noise in Calibration Information Sheet for Signal to Noise of Refractive Index Detector (Annexure-IV).
Set the following parameters:
Flow Rate : 1.0 ml/min
Column Temperature : 40.0°C
Run Time : 2.0 min
Injection Volume : 20.0 µl
Sample : RID Std kit
Evaluation Compound : Glycerin
[][]Check the area and height and find the R/F, R/F average, R/F STD and Coefficient of Determination.
[][]Record the linearity in Calibration Information Sheet for Response Linearity of Variable Wavelength Detector (Annexure-IV).
[][]High Performance Autosampler: 1260 ALS
[][]Check the LED is on.
[][]Turn on the power.
Set the following parameters:
Injection Volume : 20 µl
Run Time : 2.0 min
Flow Rate : 1.0 ml/min
Column Temperature : 40.0°C
Wavelength : 273 nm
Sample : Caffeine Std
Evaluated Compound : Caffeine
Standard Concentration : 25 µg/ml (from Certificate of Analysis)
[][]Check the Area and Height of six chromatograms and calculate average value, standard deviation and %RSD.
[][]Record the value in Calibration Information Sheet for High Performance Autosampler (Annexure-V).
Set the following parameter:
Injection Volume : 20 µl
Run Time : 2.0 min
Flow Rate : 1.0 ml/min
Column Temperature : 40.0 °C
Wavelength : 273 nm
Sample : Caffeine Std
Evaluated Compound : Caffeine
Standard Concentration : 25 µg/ml (from Certificate of Analysis)
[][]Check the Carry Over of Injection.
[][]Record the Carry Over in Calibration Information Sheet for Injection Carry Over of High Performance Autosampler (Annexure-V).
[][]Cleaning procedure
[][]Clean the instrument daily as follows
[][]Switch ‘OFF’ the instrument and switch ‘OFF’ the mains.
[][]Clean the outer surface of the instrument with dry clean cloth.
[][]Clean the surrounding areas of instrument with a cloth dampen in water then wipe with a dry cotton cloth.
[][]Remove any dirt or spot with isopropyl alcohol and then dry with tissue paper.
[][]After completion of each analysis, clean the HPLC as follows
[][]Transfer the used glassware for washing.
[][]Clean the plunger seal by injecting distilled water three to four times with syringe.
[][]Remove the column and replace with joints for the cleaning of tubings & flush with 6N nitric acid, distilled water and then with methanol.
[][]Remove the air in suction pipe by purging the line and flushing with distilled water for some time.
[][]Clean the suction filter by sonicating it into nitric acid for 10 to 15 minutes and then wash it with water, when required.
[][]Replace the joints with column and wash the column first with distilled water and then with methanol.
[][]Switch “OFF” the pump, detector(s), injector and column compartment.
[][]Finally enter fill-up the Logbook for Operation of HPLC (Annexure-VI).

Annexure: Calibration of HPLC

Annexure-I: Calibration Information Sheet for Quaternary Pump VL
Annexure-II: Calibration Information Sheet for Thermostatic Column Compartment
Annexure-III: Calibration Information Sheet for Variable Wavelength Detector
Annexure-IV: Calibration Information Sheet for Refractive Index Detector
Annexure-V: Calibration Information Sheet for High Performance Autosampler
Annexure-VI: Logbook for Operation of HPLC

Calibration of HPLC System With Operation & Cleaning Read More »

Calibration of Oven Operation with Operation & Cleaning

Calibration of Oven , Purpose :

Calibration of Oven , The purpose of this SOP is to describe the operation, calibration and cleaning of Oven (256 L) (Brand: Memmert, Model: UNE 600) used for drying of glassware in the quality control laboratory at XX Pharmaceuticals Ltd.

Calibration of Oven , Scope :

This SOP applies for operation, cleaning and calibration of Oven (256 L) (Brand: Memmert, Model: UNE 600) in quality control laboratory of  XX Pharmaceuticals Ltd.

Definitions/Abbreviation:

Standard Operating Procedure (SOP): Standard Operating Procedure.

Responsibilities:

The roles and responsibility is as follows:

Sr. Executive/Executive, Quality Control

[][]To follow the instructions of this procedure correctly.
[][]To maintain the records properly as per SOP.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.
[][]Schedule calibration of the instrument at the defined intervals.

Manager, Quality Control

[][]Approval of SOP
[][]To ensure the overall implementation of the SOP.

Annexure:

N/A

Procedure:

General Precaution(s):

[][]Do not wipe with damped cloth at on position.
[][]Do not overload the chamber with glassware.
[][]Do not keep the items those may produce inflammation with air.
[][]Keep glassware to avoid the touch of inner surface of the chamber.
[][]Avoid opening the door for long period.
[][]Do not move the oven at on position. Severe vibrations may cause serious damage of the temperature probes.

Operation:

[][]Connect the instrument to the main power supply.
[][]Switch ‘ON’ the mains.
[][]Press push/turn control key to put on the main power switch in front of the instrument. The oven will start in normal mode with the display of timer, the chamber temperature, alarm temperature (red color indication).
[][]Hold down the SET key and turn the push/turn control key at the clockwise or anti clockwise for setting date, local time, operating temperature, alarm temperature. After setting, SET key will be released the display briefly flashes the set point.
[][]The display then changes to the actual current temperature and starts to the setting temperature. The temperature will be automatically increased at setting temperature and display the setting temperature digitally.
[][]Observe the display temperature until stable position.
[][]Hold down the SET key (appr. 3 seconds) to select the operation mode, if require. The current operating mode will be flashed on the display. There are three operating mode in the oven:

Normal Operation
Weekly Programmer
Ramp time Programme Operation

[][]Select the required programme and set as per operation manual.
[][]Select the fan speed to set the air changes.
[][]Turn the push/turn control at clockwise until the fan symbol flashing to move the air slider opens and closes the air valve to control the supply and discharge of air.
[][]Check the chamber temperature using by a calibrated digital thermometer, when the setting Temperature reaches.
[][]Keep the glassware’s inside the oven.
[][]The oven will automatically control the Temperature.
[][]The instrument will automatically adjust the temperature. When the temperature exceed the setting temperature, “off” light will illuminate and if the temperature decrease the “on” light will illuminate.

Cleaning Procedure :

[][]Switch off the oven and disconnect the power plug.
[][]Remove all glassware’s from the chamber of oven.
[][]Clean inside & outside of the chamber with dry cloth.
[][]Reload all items into the chamber when reach to dry the chamber surface.
[][]At the end of cleaning, connect the power plug and switch on the oven.
[][]Clean the chamber once in a month.
[][]Clean the outer surface of the oven every day.

Calibration Procedure:

[][]Switch ‘ON’ the mains of instrument.
[][]Set the desired temperature. Follow above operation procedure
[][]Allow sufficient time to equilibrate the set temperature.
[][]Check the temperature using a calibrated thermometer/data logger and record the temperature in the calibration certificate as per Annexure-V of Engineering SOP
[][]Carry out others two calibration temperatures in the same manner.
[][]Calibrate the oven once in a year ± 15 days.

Maintenance :

[][]If oven shows any mechanical, electrical or any others problem, inform to supplier or Engineering Department for corrective action.
[][]After corrective action, recalibrate the oven if it is necessary.

Calibration of Oven Operation with Operation & Cleaning Read More »

Atomic Absorption Spectrophotometer Calibration

Atomic Absorption Spectrophotometer Calibration, Purpose :

Atomic Absorption Spectrophotometer Calibration, The purpose of this SOP is to describe the operation and cleaning procedure of Atomic Absorption Spectrophotometer Model No. – A Analyst 400 with Graphite Furness HGA 900 used for analysis of the finished product & raw materials in the Quality Control Laboratory at XX Pharmaceuticals Ltd.

Atomic Absorption Spectrophotometer Calibration, Scope :

This procedure is applicable for the Atomic Absorption Spectrophotometer, installed in the Quality Control Laboratory of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

Standard Operating Procedure (SOP): A written authorized procedure, which gives instructions for performing operations.
QC: Quality Control.

Responsibilities:

The roles and responsibility is as follows:

Sr. Executive/Executive, QC

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]Arrange training on the SOP to all concerned personnel.
[][]To ensure implementation of the SOP after training.
[][]Schedule calibration of the instrument at the defined intervals.

Head of Quality Assurance

[][]Approval of the SOP.
[][]To ensure overall implementation of the SOP.

Procedure:

Precaution(s):

[][]Care must be taken in handling the instrument opening, putting sample, and closing especially.
[][]Ensure optimum fluid level, otherwise flame will not ignite.
[][]All the solutions must be prepared carefully.
[][]The detection chamber must be clean and free from any dust of foreign particles.
[][]The selection of correct hollow cathode lamp of a particular atom must be present on a correct position of the lamp holder.
[][]The Air conditioning system and air exhauster must be open during operation of the Instrument.

Operation

[][]Procedure for getting concentration of a particular atom in Flame Method
[][]Ensure proper cleaning of the machine before operation.
[][]Turn on the computer and printer.
[][]Turn on the switch of the instrument.
[][]Turn on the switch of air compressor.
[][]Let open the exhaust switch for a few minutes of the compressor to expel moisture from it.
[][]Close the exhaust switch to retain huge amount of compressed air in it.
[][]Set the accessories apparatus of the flame mode.
[][]Turn on the switch of the Flame mode.
[][]Turn on the operating software on the computer.
[][]Align and optimize the instrument.
[][]Turn the screw of the acetylene gas cylinder and ensure its proper flow to the ignition chamber.
[][]Method setting: A method set by following way-
[][]At first click to file manager.
[][]Then go to new and click to method.
[][]Select the element (test element) from starting condition and click OK.
[][]Click on spectrometer at define element & write the method name in method description.
[][]Then select AA/AA-BG (as per method) from signal option.
[][]Click on setting and select the time, delay time & replicates.
[][]Click on sampler and select Air from Oxidant.
[][]Click on calibration and select Linear Through zero then select results unit (ppb, ppm etc) from equation & units.
[][]Click on standard concentration & select Blank and standard (1, 2, 3 etc).
[][]Then check sequence setting: set the number of standard and samples sequentially and save it.
[][]Then check sequence setting: set the number of standard and samples sequentially and save it.

[][]After completion the program, arrange & displayed the results window, the calibration window, the manual analysis control window and the flame control window from monitor window bar.
[][]Click “ON” button on the right side of the Flame option.
[][]Then follow the instruction of the software and input information accordingly.
[][]After completion of the calibration curve input sample according to software instructions.
[][]After completing analysis print the output or it may be saved.
[][]Turn off the software.
[][]Turn off the gas flow.
[][]Turn off the main instrument and expel air from compressor.
[][]Turn off the Switch of the computer.

Cleaning

[][]Clean all parts of the machine with cotton cloth using methanol after use.
[][]Procedure for getting concentration of a particular atom in Graphite Method
[][]Ensure proper cleaning of the machine before operation.
[][]Turn on the computer and printer
[][]Turn on the switch of the instrument
[][]Turn on the switch of air compressor
[][]Let open the exhaust switch for a few minutes of the compressor to expel moisture from it
[][]Close the exhaust switch to retain huge amount of compressed air in it.

[][]Set the accessories apparatus of the Graphite mode.
[][]Check the cooling system, the water level retain between maximum and minimum level.
[][]Turn on the switch of the Graphite mode.
[][]Turn on the operating software on the computer.
[][]Align and optimize the instrument.
[][]Turn the screw of the Argon gas cylinder and ensure its proper flow to the ignition chamber.
[][]Method setting: A method set by following way-
[][]At first Click to file manager.
[][]Then go to new and click to method.
[][]Then go to new and click to method.
[][]Then select the element (test element) from starting condition and click OK.
[][]Then go to spectrometer at define element & write the method name in method description and select AA/AA-BG from signal option. (as per method)
[][]Click on setting and select the time, delay time, BOC time & replicates.
[][]Click on sampler and go to Furness program & select Temperature, Ramp time, Hold time, internal flow & gas type.
[][]Click on Autosampler and select sample volume, Diluent location, matrix modifiers volume & location.
[][]Click on calibration and select Linear Through zero from calibration equation.
[][]Then select result unit (ppm, ppb etc) from equation and unit.
[][]Click on standard concentration & select Blank and standard (1, 2, 3 etc).
[][]Click on calculate standard volume & select stock standards, location & concentrations. Select the location of blank & reagent blank. Then click to OK and save it.
[][]Then click on Displayed the sample information editor. Write sample location and sample ID then save as in sample information file.
[][]Click on Auto (Automated analysis control)
[][]Click on Open from results data set name (for Data save).

[][]Click on analyze.

[][]After completion the program, arrange & displayed the results window, the calibration window, the automated analysis control window and the Furness control window from monitor window bar.
[][]Then click on analyze all
[][]Then follow the instruction of the software and input information accordingly
[][]After completion of the calibration curve automatically input sample according to software instructions.
[][]After completing analysis print the output or it may be saved.
[][]Turn off the software.
[][]Turn off the gas flow.
[][]Turn off the main instrument and expel air from compressor.
[][]Turn off the Switch of the computer.

Cleaning

[][]Clean all parts of the machine with cotton cloth using methanol after use.
[][]Procedure for getting concentration of a particular atom in MHS Method
[][]Ensure proper cleaning of the machine before operation.
[][]Ensure proper cleaning of the machine before operation.
[][]Set the MHS part with AAS properly.
[][]Set the sample tube on the flame chamber properly.
[][]Turn on the computer and printer.
[][]Turn on the switch of the instrument.
[][]Turn on the switch of air compressor.
[][]Let open the exhaust switch for a few minutes of the compressor to expel moisture from it.
[][]Close the exhaust switch to retain huge amount of compressed air in it.
[][]Turn on the switch of apparatus of the Graphite mode.
[][]Check the cooling system, the water level retain between maximum and minimum.
[][]Turn on the switch of the Flame mode.
[][]Turn on the operating software on the computer.
[][]Align and optimize the instrument.
[][]Turn the screw of the Argon & acetylene gas cylinder and ensure its proper flow to the ignition chamber.
[][]Method setting: A method set by following way-
[][]At first Click to file manager.
[][]Then go to new and click to method.
[][]Select the element (test element) from starting condition and click OK.
[][]Then go to spectrometer at define element & write the method name in method description.
[][]Click on setting and select the time, delay time, BOC time & replicates.
[][]Then click on sampler and go to Furness program & select Temperature, Ramp time,
[][]Hold time, internal flow & gas type.
[][]Click on calibration and select Linear Through zero from calibration equation.
[][]Then select result unit (ppm, ppb etc) from equation and unit.
[][]Click on standard concentration & select Blank and standard (1, 2, 3 etc).
[][]Then check sequence setting: set the number of standard and samples sequentially and save it.
[][]After completion the program, arrange & displayed the results window, the calibration
[][]window, the manual analysis control window and the flam control window from monitor window bar
[][]Then click “ON” button on the right side of the Flam option.
[][]Then follow the instruction of the software and input information accordingly
[][]After completion of the calibration curve input sample according to software instructions.
[][]After completing analysis print the output or it may be saved.
[][]Turn off the software.
[][]Turn off the gas flow.
[][]Turn off the main instrument and expel air from compressor.
[][]Turn off the Switch of the computer.

Cleaning

Clean all parts of the machine with cotton cloth using methanol after use.

Calibration:

Calibration for Flame System:
Wavelength Accuracy Using Ni:

Test Conditions:

[][]Open the default Nickel method (File-New-Method-Ni)
[][]Open the continuous Graphics window so the system will set up for Nickel.
[][]Ensure the lamp has been on for 15 minutes before measuring g absorbance with the Nickel standard.

Test prerequisites:

[][]Burner position Optimized and Nebulizer adjusted using Copper.

Test Steps:

[][]Under the tool bar, double click on the instrument icon in the ‘Spectrometer status panel’ to open the diagnostic/spectrometer window.
[][]Select the ‘Optical Position’ button at the button of the diagnostics window.
[][]Select the ‘Optical Position’ button at the button of the diagnostics window.
[][]A graphic plot of the peaked positions for the prism and Grating will be displayed

The Prism Tolerance is ±190 motor steps
The Grating Tolerance is +380, -260 motor steps

Sensitivity and Precision Using Ni:

Apparatus:

Volumetric flask with stopper, 1000 ml
Glass pipette 3 ml
Beaker 10 to 200 ml

Reagents:

1000 ppm Ni AAS standard solution.
Nitric acid

Preparation for 3ppm Ni standard solution:

[][]Pour a small quantity of 1000 ppm Ni AAS standard solution in the beaker. Use it to rinse the 3 ml pipette and the beaker, then discard it.
[][]Pour another 5ml (minimum) 1000ppm Ni AAS standard solution into the beaker.
[][]Pipette 3 ml standard from the beaker into the 1000 ml volumetric flask.
[][]Half fill the volumetric flask with de-ionized water.
[][]Pour 10 ml (approximately) of nitric acid into the volumetric flask.
[][]Fill the volumetric flask with de-=ionized water exactly to the mark.

Note: 3ppm Ni standard should be produced before the day of test.

Test Steps:

Edit the Nickel default method and enter/verify the following parameter:
Signal type: A
Read time:10.0
Replicates: 10

[][]While in the method editor, go to the calibration/ standard concentrations page. Enter blank for calibration blank ID and Nickel standard for standard ID.
[][]In the ‘Flame Control’ window, select the ‘Flam On/off’ icon to light the flame.
[][]In the ‘Manual Analysis Control’ window, aspirate blank and select ‘Analysis Blank’. 10 Replicates will be measured and autozero will occur.
[][]Aspirate a 3ppm Ni standard and select ‘Analysis Sample’. 10 Replicates will be measured.
[][]The results will be displayed in the result window. Record the values for mean absorbance and relative standard deviation (RSD).The value should meet following requirements.

Mean Absorbance ≥ 0.200
RSD ≤ 0.3%

[][]Return to the ‘Flame Control’ window and extinguish the flame by pressing Flame On/Off.

Wavelength Accuracy Using As:

Test Conditions:

[][]Open the default Arsenic method (File-New-Method-Ni)
[][]Open the continuous Graphics window so the system will set up for Arsenic.
[][]Ensure the lamp has been on for 15 minutes before measuring absorbance.

Test prerequisites:

[][]Burner position Optimized and Nebulizer adjusted using Copper.

Test Steps:

[][]Under the tool bar, double click on the instrument icon in the ‘Spectrometer status panel’ to open the diagnostic/spectrometer window.
[][]Select the ‘Optical Position’ button at the button of the diagnostics window.
[][]A graphic plot of the peaked positions for the prism and Grating will be displayed.
The Prism Tolerance is ±200 motor steps
The Grating Tolerance is ±380 motor steps

[][]Select the ‘X’ in the upper right hand corner to exit the ‘Optical position’ window. Select the X in the Upper right corner to close the window.

AA-BG Baseline Noise at 1 Abs. Using As:

Test Steps:

Edit the Arsenic default method and enter/verify the following parameter:

Signal type:AA-BG
Read time: 2
Replicates: 99

[][]In the Manual Analysis Control window, select the ‘Analyze blank’ button. The system will take 99 readings and perform an autozero.
[][]Insert the 1.0 A neutral density filter into the filter holder.
[][]In the Manual Analysis Control window, select the ‘Analyze Sample’ button. When the reading is complete, record the SD value. It should be ≤ 0.005.

AA Baseline Noise and Drift using Cu:

Test prerequisites:

[][]Burner position Optimized and Nebulizer adjusted using Copper.
[][]Copper lamp should be warmed up at least 15 minutes.

Test Steps:

[][]Open the default Copper method (File-New-Method-Ni)
[][]Open the continuous Graphics window so the system will set up for Copper.
[][]Edit the Copper default method and enter/verify the following parameter:
Signal type: AA
Read time: 0.5
Replicates: 99

[][]In the Manual Analysis Control window, select the ‘Analyze blank’ button. The system will take 99 readings and perform an autozero.
[][]In the Manual Analysis Control window, select the ‘Analyze Sample’ button. Data collection for 99 replicates will begin.
[][]At the end of 99 replicates, record the standard deviation (SD) value in the table below. It should be ≤0.001. Record the mean absorbance value as well.
[][]Wait 15 minutes and repeat the measurement. Record the mean absorbance value for the second measurement.
[][]Calculate the difference between the absorbance measurements. It should be ≤ 0.002 Abs.

Wavelength Accuracy Using Cu:

Test Steps:

[][]Under the tool bar, double click on the instrument icon in the ‘Spectrometer status panel’ to open the diagnostic/spectrometer window.
[][]Select the ‘Optical Position’ button at the button of the diagnostics window.
[][]A graphic plot of the peaked positions for the prism and Grating will be displayed.

The Prism Tolerance is ±120 motor steps
The Grating Tolerance is ±380 motor steps

[][]Select the ‘X’ in the upper right hand corner to exit the ‘Optical position’ window. Select the X in the Upper right corner to close the window.

Copper Capacitance:

The Optical position box also displays two capacitances values. Cap: in the upper left corner. The first value is the cap: used for peaking and the last value is the Final Cap: Record the Final Cap. It should be ≥1.0 pF

Flame Sensitivity and Precision using Cu:

Apparatus:

Volumetric flask with stopper, 1000 ml
Glass pipette 2 ml
Beaker 10 to 200 ml

Reagents:

1000 ppm Cu AAS standard solution.
Nitric acid.

Preparation for 2ppm Cu standard solution:

[][]Pour a small quantity of 1000 ppm Cu AAS standard solution in the beaker. Use it to rinse the 2 ml Pipette and the beaker, then discard it.
[][][][]Pour another 5ml (minimum) 1000ppm Cu AAS standard solution into the beaker
Pipette 2 ml standard from the beaker into the 1000 ml volumetric flask.
[][]Half fill the volumetric flask with de-ionized water.
[][]Pour 10 ml (approximately) of nitric acid into the volumetric flask.
[][]Fill the volumetric flask with de-=ionized water exactly to the mark.

Note: 2ppm Ni standard should be produced before the day of test.

Test Steps:

[][]Edit the Copper default method and enter/verify the following parameter:
Signal type: AA
Read time:10.0
Replicates: 10
[][]In the ‘Flame Control’ window, select the ‘Flam On/off’ icon to light the flam.
[][]In the ‘Manual Analysis Control’ window, aspirate blank and select ‘Analysis Blank’. 10 Replicates will be measured and autozero will occur.
[][]Aspirate a 2ppm Cu standard and select ‘Analysis Sample’. 10 Replicates will be measured.
[][]The results will be displayed in the result window. Record the values for mean absorbance and relative standard deviation (RSD).The value should meet following requirements.
Mean Absorbance ≥ 0.250
RSD ≤ 0.30%
[][]Select the Spectrometer- Setting tab and enter/verify the following parameter:
[][]Signal type: AA

Read time:0.1
Replicates: 10

[][]In the ‘Flame Control’ window, select the ‘Flam On/off’ icon to light the flam.
[][]In the ‘Manual Analysis Control’ window, aspirate blank and select ‘Analysis Blank’. 10 Replicates will be measured and autozero will occur.
[][]Aspirate a 2ppm Cu standard and select ‘Analysis Sample’. 10 Replicates will be measured.
[][]The results will be displayed in the result window. Record the value for relative standard deviation (RSD).The value should meet following requirements.
RSD ≤ 3.0%
[][]Return to the ‘Flame Control’ window and extinguish the flame by pressing Flame On/Off.

Calibration for Flame System:

Chromium Baseline Noise For Furness:

Test Steps:

[][]Click on the File pull down menu, then on Open. Select Method.
[][]Click on Browse. Go up 2 levels and double-click on Service. Then double click on Method.
[][]Double click on HGA Cr Test method. Select the Method Ed icon to open the Method Editor window.
[][]In the spectrometer section, select set. Select 2.7 Slit Width and 0.8 Slit Height. Select OK. Click on the file pull down menu, then on Save. Select Method. Close the Method Editor window.
[][]Click on the Tools pull down menu and then select Continuous Graphics. This will set up the Lamp. Close the Continuous Graphics window.
[][]Open the Align lamps window. Look at the Bar Graph status window and verify that the Cr HCL Lamp current is 15 mA and the Slit is se4t to 2.7/0.8. Also verify that the Background corrector is On. Allow the lamp to warm up for 30 minutes.
[][]Close the Align Lamps window.
[][]From the Tools pull down menu open the windows Results, Peaks and Automated Analysis. Arrange and align the windows as desired.
[][]Open the Furness control window and select the Furness ON/Off button to run at least one dry firing (without any sample) to make sure that there is no residual signal (Peak area less than 0.005) from any previous injections or tube contamination.
[][]Make sure position 3 of the Autosampler is empty. Type in 3 as the sample lactation in the setup page of the Automated Analysis window, click on the Analyze tab and then on the Analyze Samples button to measure 5 Furness dry firings (without any sample).
[][]Ensure that the AA and BG signals do not diverge from the baseline. Realign the Furness into the optical beam if necessary.
[][]The standard deviation of the mean dry-firing result in integrated absorbance (Peak area) for the Cr wavelength must not exceed a maximum value of 0.002. Record the result.

Chromium Characteristic Mass and Precession:

Test Steps:

[][]Use the same method as in the previous test. Demonized water should be in position 1 and Cr standard should be in position 2 of the Autosampler.
[][]Type in 2 as the sample lactation in the setup page of the Automated Analysis window, click on the analyze tab and then on the Analyze Samples button to measure 5 furnace firings using 20 µl sample injections.
[][]Calculate the characteristic mass using the Calculate characteristic mass tool from the Analyses pull down menu.

Characteristic Mass Result:

The characteristic mass (m0) results in pg and calculated from the mean integrated absorbance (Peak area) values should lie within the following ranges:

Element: Cr

Lower Limit (pg): 2.3

Target Value (pg): 3.0

Upper Limit (pg): 3.8

Note: If the characteristic mass exceeds the lower limit, check for possible contamination of the water used for sample preparation. Prepare a new solution if required.

Precision:

[][]The relative standard deviation (%RSD) of the mean sample solution readings calculated from the integrated absorbance (peak area) values for Cr must not exceed the maximum value of 2.0%.
[][]Record the results in the OQ Test Certificate on page 40.
[][]AS-800 Autosampler Linearity
[][]Click on the File pull down menu, then on Open. Select Method.
[][]Verify that you are in the Service\Methods directory. If not, click on Browse. Go up 2 levels and double-click on Service. Then double click on Method.
[][]Double click on HGA AS-800 Lin method.
[][]Select the Method icon to open the Method Editor window.
[][]In the spectrometer section, select Set. Select 2.7 Slit Width and 0.8 Slit Hight. Select OK.
[][]On the right side of the Method window select the Settings tab.
[][]In the Lamp Current section, select Use current (mA) and then type 15 in the Lamp Current box.
[][]Click on the File pull down menu, then on Save. Select Method.
[][]Close the Method Editor window.
[][]Clock on the Tools pull down menu and then select Continuous Graphics. This will set up the Lamp. Close the Continuous Graphics windows.
[][]Open the Align lamps windows. Look at the Bar Graph status window and verify that the Cr HCL Lamp current is 15mA and Slit is set to 2.7/0.8. Also verify that the Background Correction is ON. Allow the lamp to warm up for 30 minutes (if not already warmed up).
[][]Close the Align Lamps window.
[][]From the Tools pull down menu open the windows Results, Peaks, Examine Calibration and Automated Analysis. Arrange and align the windows as desired.
[][]Click on the Analyze tab of the Automated Analysis window and then on the Calibration button top start the calibration.
[][]When the calibration is finished check the Correlation Coefficient Result in the Examine Calibration window.
[][]The Correlation Coefficient Result Cr must exceed the minimum value of 0.999.

Annexure: Atomic Absorption Spectrophotometer Calibration

Annexure-I: Calibration Information Sheet for Wavelength Accuracy, Sensitivity and Precision using Ni
Annexure-II: Calibration Information Sheet for Wavelength Accuracy and AA-BG Baseline Noise at 1 Abs. using As
Annexure-III: Calibration Information Sheet for Baseline Noise, Wavelength Accuracy, Copper Capacitance, Flame Sensitivity and Precision using Cu
Annexure-IV: Calibration Information Sheet for Baseline Noise, Characteristic Mass and Precession, Autosampler Linearity using Cr
Annexure-V: Operation logbook for Atomic Absorption Spectrophotometer

Atomic Absorption Spectrophotometer Calibration Read More »

Wash Water from production equipment sampling & analytical procedure

Wash Water, Purpose:

Wash Water, The purpose of this SOP (Standard Operating Procedure) is to define the Sampling and analytical procedure for wash water.

Wash Water, Scope:

This procedure is applicable for sampling of wash water from production equipments and analysis of wash water in the Quality Control laboratory  of XX Pharmaceuticals Ltd.

Definition:

None

Responsibilities:

The roles and responsibility is as follows:

Executive, Production

[][]To co-ordinate to collect the sample as per defined procedure
[][]To send duly filled Wash Water Sampling Advice Form to QC/QA Department.
[][]To maintain the proper documentation.

Sr. Executive/Executive, Quality Assurance

[][]To withdraw the sample as per the defined procedure.

Sr. Executive/Executive, QC

[][]To analyze the sample as per defined procedure
[][]To ensure that this procedure is kept up to date.

Manager, Quality Control

[][]To ensure appropriate personnel from the section are trained on this procedure.
[][]To confirm that SOP is technically sound and reflects the required working practices.

Head of Quality Assurance

[][]To ensure the overall implementation of the SOP.
[][]Approval of the SOP.

Procedure:

[][]Production personnel clean the equipment as per standard cleaning procedure, intimates QC/QA for wash water sampling with the “Wash Water Sampling Advice Form” in duplicate.
[][]Quality Compliance representative inspects the equipment and its parts for cleanliness and then collects the sample as follows:

Vibratory Shifter:

[][]Attach the sieve on the body of the sifter and wash with 3.0 L of Purified water and collect the sample at the receiver into a clean bowl. Rinse the dismantled parts (Lid, clamp, hopper and silicon gasket) with 2 liters of purified water and collect into the same bowl. Collect approx. 30 ml of the sample into an amber colored bottle for analysis.

Container Blender:

[][]Rinse the colloid mill with 3.0 L of Purified water and collect it into a clean bowl. Collect 30ml of the sample into an amber colored bottle from the bowl for analysis.

Rapid Mixer Granulator:

[][]Rinse the equipment bowl and top lid with 30.0L of Purified water and collect the water into a clean bowl through the discharge taking care that the whole surface of the bowl and top lid is rinsed properly and rinse the dismantled parts (clamp for binder addition, charging port, spray nozzle, vent filter, chopper blade, impeller blade discharge valve and all gaskets) with 5 liters of purified water and collect into the same bowl. Collect approximately 30 ml of sample into an amber colored bottle for analysis.

FBD (Fluid Bed Drier):

[][]Rinse the retarding chamber internally with 10.0 L of Purified water and collect it into a clean bowl. Collect approximately 30 ml of the sample into an amber colored bottle for analysis. Similarly rinse the FBD trolleys with 10.0 L of Purified water each and collect 30ml of the sample separately from the two bowls. Rinse the cartridge filters/FBD bag with 5-liters of purified water and collect the water into the clean bowl. Collect approximately 30 ml of the sample into an amber colored bottle for analysis.

Tablet Coating Machine:

[][]Rinse the pan with 10.0L of Purified water and collect the sample into a clean bowl through the discharge taking care that the whole surface and the Baffles are rinsed properly. Rinse the dismantled parts (Silicon tube, Gun assembly, inlet duct and outlet duct) with 5 liters of purified water and collect into the same bowl. Collect approximately 30 ml of the sample into an amber colored bottle for analysis.

Compression machine:

[][]Rinse the hoppers, butterfly valve, triclover clamp, force feeder, inlet connector, Turret guards, Powder scrapper, Acrylic guards, feeder shaft, Exhaust pipes with 5 liters of purified water and collect in a clean bowl. Collect approximately 30 ml of this sample into an amber colored bottle for analysis. Similarly rinse the y – chute, Gravity pipe with 5 liters of purified water and collect in the clean bowl. Collect approximately 30 ml of this sample into an amber colored bottle for analysis.

Capsule Filling Machine:

[][]Rinse the capsule loading channel, hopper, Loading ring, Auger, Locking pin assembly with 5 liters of purified water and collect in to clean bowl. Collect approximately 30 ml of this sample into an amber colored bottle for analysis.

Capsule polishing Machine:

[][]Rinse S.S cover of polishing Machine and polishing brush with 2 liters of purified water and collect in to clean bowl. Collect approximately 30 ml of this sample into an amber colored bottle for analysis.
[][]While collecting wash water sample, collect Purified water about 30 ml into an amber colored bottle.
[][]Use this as blank.

Note: For the equipments, which are not specified above, use 2.0 L, 5.0 L, & 10.0 L as the rinsing water quantity depending on the size i.e. small, medium & big.

Analysis:

[][]After getting sampling advice form from production department, QC personnel will entry in the wash water register and assign a lab control number as WW-000X/MM/XX(where WW for Wash Water, 000X- Sequential number of four digits, MM-Month and YY-Last two digits of year. For example: WW-0001/08/XX). Then the compliance personnel will collect the sample and send to Quality Control department for analysis.
[][]QC analyses the sample by scanning through 190-400 nm on UV-VIS Spectrophotometer, using Purified water (collected as explained earlier) as blank.
[][]Observe for any abnormal peaks and/or peaks having same wavelength maximum of active material of previous product.
[][]Reject the sample in case of any abnormal peak or if a peak of previous product having more absorbance that of a 10 ppm standard solution of active of previous product and send the information to the concerned department.
[][]Take the spectrum print out on the back side of the wash water report copy (QC copy) and inform production for rewash.
[][]If absorbance is less than that observed in standard graph, intimate the concerned department by sending the original copy of the report after making necessary entries and approving the clean card. Retain the duplicate copy of the report and file it after making necessary entries in the register.

Annexure:

Annexure-I: Wash Water Sampling Advice Form.
Annexure-II: Wash Water Register.

Wash Water from production equipment sampling & analytical procedure Read More »

Out Of Specification (OOS) Handling and Investigation

Out Of Specification (OOS), Purpose :

Out Of Specification (OOS), The purpose of this SOP is to define the procedure for handling of OOS results in the Quality Control Laboratory of XX Pharmaceuticals Ltd.

Out Of Specification (OOS),Scope :

[][]This SOP is applicable for all Out of Specification (OOS) results detected during testing of any product or materials in Quality Control Laboratory of general block of XX Pharmaceuticals Limited.
[][]If an out of specification results is generated for dissolution/ Drug release, uniformity of dosage units, weight variation, disintegration test, In process sample and any other test which is used to measure variability in a lot this SOP does not apply. In such cases respective Pharmacopoeial guidelines or criteria shall be apply.
[][]This SOP does not apply to samples of various stages like In process samples, Intermediate samples, scale up batches, method validation, method development, solvents, packaging material, wash water, decontamination samples, evaluation samples, raw material received from new vendor, description and solubility test, tests where tentative limits given.
[][]This SOP does not apply for OOS to tests like Bulk density, Sieve analysis, Particle size and other physical parameters.
[][]This SOP does not apply when system suitability failure, bracketing standard, transcriptional errors or processing method errors (In case of failure due to the integration parameters for the HPLC).
[][]This SOP does not apply to incomplete analysis where result is not derived.
[][]Out of Specification is not applicable for out laboratory testing.

Definitions / Abbreviation:

[][]Standard Operating Procedure (SOP): Standard Operating Procedure. A written authorized procedure, which gives instructions for performing operations.
[][]QC: Quality Control.
[][]CAPA: Corrective action and preventive action.
[][]OOS result: An OOS result is a result from a defined test procedure that fails to meet established specifications or criteria. An OOS result does not constitute a failure unless further investigation confirms this result.
[][]Atypical result: Results that are still within specification but are unexpected, questionable, irregular, deviant or abnormal.
[][]Obvious error : Obvious error can be occurred due to:
Calculation Error
Laboratory error
[][]Laboratory Error: A mistake that occurs within the test laboratory caused by an analyst or piece of equipment. Examples include use of incorrect standards, improper sample or standard preparation, improperly calibrated balances, equipment failure and miscalculations.
[][]Laboratory Investigation: The investigation that is conducted within the laboratory to determine the cause of the OOS results.
[][]Assignable Cause: An identified reason for obtaining an OOS or aberrant/anomalous result.
[][]No Assignable Cause: When no result could be identified.
[][]Review: To check all critical parameters involved in the test which may cause of the OOS results.
[][]Reanalysis: Further analysis with the same dilution of sample or of same aliquots which produced OOS results.
[][]Retest: Re-examining the material from the original sample that was used as the source of the aliquot that produced OOS result.
[][]Resample: A new sample from the original container where possible, required in the event of insufficient material remaining from original sample composite or proven issue with original sample integrity.

Responsibilities:

The roles and responsibility is as follows:

Executive, QC

[][]Analysis of any product or materials and to notify the OOS results to supervisor.

Sr. Executive, QC

[][]To ensure the initial investigation of the test parameters and to organize the testing.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP reflects the required working practices.
[][]To make decision for re-sampling.
[][]To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.

Head of Quality Assurance

[][]Approval of the SOP.
[][]To take the final decision to release the batch.
[][]To ensure the overall implementation of the SOP.

Procedure:

[][]The procedure mentioned below shall be followed if a Laboratory result for raw materials sample, In-process Sample or Finished Product sample fails to meet the Specification.
[][]Analyst shall not destroy the sample preparation / solution and shall retain the prepared solutions, Standards and Sample solutions until the investigations have been concluded.
[][]Retain all Glassware, Blend & Finished Product Sample.
[][]Check the whole analysis for compliance (Self-check).
[][]Inform immediately to the Supervisor about the OOS result.
[][]Supervisor will discuss with the analyst about the test method and confirm analyst knowledge of and performance of the correct procedure.
[][]Check if a laboratory error could be the cause of OOS results and inform Manager, QC.
[][]Check and record the present conditions in Notification of out of specification (OOS) result as per Annexure-I.
[][]Follow the Flow Chart (Annexure-II) for OOS Investigation
[][]The QC Manager should assess the data promptly to ascertain if the results may be attributed to laboratory error, or whether the results could indicate problems in the manufacturing process.

[][]It is to be clarified together with the QC Manager whether there is an apparent analytical error. A formal check is to be carried out (Investigation stage 1) using Out of Specification (OOS) Results Investigation Checklist (Annexure – IV) which shall be issued by QC Manager making entry in the Out of specification investigation register (Annexure – III) and assigning sequential number as below:
e.g. OOS-001/xx
Where, OOS is the abbreviation of Out of Specification
001 is the sequential number of Out of Specification investigation
/ is separator
xx is last two digits of year 20xx

[][]At the first step, the QC Manager along with Analyst shall immediately try to find out any obvious Error (Example: Calculation error, Power outage, Equipment failure, Testing Error, Incorrect Instrument Parameters etc.)
[][]If any calculation error is found out, make correction the calculation and release the material/product; analyst shall be re-trained for the error parts.
[][]If the calculation / documentation are correct, proceed with the investigation of the stepwise analysis which may include re-examination of the actual solutions, test units, glassware used in the original measurements and preparations.
[][]The following steps should be taken as part of the investigation:
[][]Discuss the test method with the analyst; confirm analyst knowledge of and performance of the correct procedure.
[][]Examine the raw data obtained in the analysis, including chromatograms and spectra, and identify anomalous or suspect.
[][]Confirm the performance of the instruments.
[][]Determine that appropriate reference standards, solvents, reagents, and other solutions were used and that they meet quality control specifications.
[][]Evaluate the performance of the testing method to ensure that it is performing according to the standard expected based on method validation data.
[][]Document and preserve evidence of this investigation.
[][]Where a transient equipment malfunction or other problem in the dosage form (e.g. incomplete extraction) is suspected, re-inject the retained sample preparations to assign a cause for OOS results.
[][]When laboratory error is identified, determine the source of that error (root cause) generating CAPA as per the SOP for ‘Corrective and Preventive Action’  and take corrective action to ensure that it does not occur again. Recommend on Out of Specification (OOS) Results Investigation Checklist (Annexure – IV) for performing a repeat analysis on the same sample with the same analyst. If the repeat analysis result is passing, void the initial result and approve the batch based on the re-test result.
[][]If no apparent analytical error can be found, i.e. evidence of laboratory error remains unclear, investigation stage 2 should be conducted to determine what caused the unexpected results, which may include re-testing and/or re-sampling and further investigation.
[][]Before further investigations are carried out during the next step, the subsequent procedure has to be written down in the testing protocol (Annexure – IV).
Tasks in testing protocol:
“What” is to be done (retesting, re-sampling, etc.)?
“Who” will be carrying out the investigations (1st analyst, 2nd analyst, etc.)?
“How” will the investigations be carried out, which equipment, which reagents, additional analysis of reference samples (state batch and number of analysis)?
“How often” will the analysis be repeated (final criterion to prevent “analysis” into
“compliance”)?
[][]A justification for the procedure must be given by the QC manager prior to implementation of the testing protocol and the test plan must be approved.
The number of retests should be 3 times or more
[][]The investigation may involve re-testing a portion of the original sample. The sample used for the retesting should be taken from the same homogeneous material / product that was originally collected for the lot/batch, tested and yielded the OOS result. For a liquid, it may be from the original unit liquid product or composite of the liquid product; for a solid it may be an additional weighing from the same sample composite that had been prepared by the analyst.
[][]Decisions to retest should be based on the objectives of the testing and sound scientific judgment. Retesting should be performed by an analyst other than the one who performed the original test.
[][]If the result is within specification (passes), the material/product shall be re-analyzed by first analyst with the same sample and to investigate the first analyst.
[][]If investigation of first analyst found satisfactory then release the material/product
[][]If the material/product fails by the second analyst also, simultaneously analyze after re-sample with the previously approved material/product.
[][]Re-sampling should involve analyzing a specimen from the collection of a new sample from the batch. A re-sampling of the batch should be conducted if insufficient quantity of the original sample remains to perform all further testing or if the investigation shows that the original sample was not representative of the batch. This would be indicated, for example, by widely varied results obtained from several aliquots of the original composite (after determining there was no error in the performance of the analysis). Re-sampling should be performed by the same qualified, validated methods that were used for the initial sample. However, if the investigation reveals that the initial sampling method was in error, a new accurate sampling method must be developed, qualified and documented.
[][]If previously approved material/product passes within the specification and material/product under investigation meets the specification, release the material/product.
[][]In case of material if previously approved material passes within the specification and material under investigation fails to meet the specification, material shall be rejected.
[][]In case of product if previously approved product passes within the specification and product under investigation fails to meet the specification, the laboratory investigation may be extended to review the quality of the materials (raw & primary packaging) used in manufacturing of the finished product. If any problem in quality of the materials is identified which may have potential effect on the OOS scenario, the root cause will be attributed to that problem.
[][]The procedure is then to be implemented and the results be evaluated. The results are to be summarized in Annexure – VI (report level 2).
[][]Conclusion must be drawn and it must be stated which individual values will be entered in the result (on Certificate of Analysis).
[][]The error category of the initial OOS result must also be recorded.
[][]At measures, a statement must be made explaining how similar OOS results are to be avoided in future.
[][]During investigation of an OOS result, review the previous investigation reports to determine whether a similar occurrence has taken place.
[][]When the laboratory investigation does not determine that laboratory error caused the OOS result and testing result appears to be accurate, the laboratory investigation/report to be handed over to QA manager for a full-scale failure investigation as per the SOP for ‘Deviation Procedure’.
[][]In case the process error is identified during failure investigation, suitable corrective action shall be taken. Sample shall then be analyzed as per routine procedure and accordingly release, if the results are okay.
[][]Quality Assurance Manager will initiate the CAPA based on root cause found in the failure investigation. CAPA must be implemented within agreed time lime. All CAPAs must be implemented based on criticality.

Annexure:

Annexure-I: Notification of Out of Specification Result
Annexure-II: Flow Chart for OOS Investigation
Annexure-III: Out of Specification (OOS) Register
Annexure-IV: Out of Specification (OOS) Investigation Checklist
Annexure-V: Out of Specification (OOS) Testing Protocol
Annexure-VI: Out of Specification (OOS) Investigation Report

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Shaking Water Bath Calibration with operation and cleaning

Shaking Water Bath Calibration, Purpose :

Shaking Water Bath Calibration, The purpose of this SOP is to describe the operation, calibration and cleaning of Shaking Water Bath (Model: Clifton, NE5-28D).

Shaking Water Bath Calibration, Scope :

This procedure is applicable for Shaking Water Bath (Model: Clifton NE5-28D), installed in the quality control laboratory of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure
[][]QC: Quality Control
[][]LED: Light-emitting diode

Responsibilities:

The roles and responsibility is as follows:

Sr. Executive/Executive, QC

[][]To ensure that the instructions of this procedure are correctly followed.
[][]To maintain the record properly as per SOP.
[][]To ensure cleaning of shaking water bath maintaining safety rules.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.
[][]Schedule calibration of the instrument at the defined intervals.

Head of Quality Assurance

[][]Approval of the SOP
[][]To ensure the overall implementation of the SOP.

Procedure:

General precautions or operational safety:

[][]Laboratory coat, hand gloves and safety glasses must be worn while handling the instrument.
[][]Always follow good laboratory practice by ensuring substances being heated offer no risk of a hazard (explosion, implosion or release of toxic or flammable gases) or that these have been addressed. When heating substances where liberating of gases occurs suitable extraction should be used.
[][]If this product is not used in accordance with these instructions, then basic safety protection afforded by the water bath may be affected.
[][]Check the operation of over temperature device regularly.
[][]The main supply cord fitted to this product is a heat resistant type and should be replaced by an equivalent type.
[][]Always use the display or a thermometer to check the temperature. Never touch the liquid within the bath as it may be very hot.
[][]Always disconnect the bath from the electric supply before cleaning.
[][]Allow the liquid in the bath to cool down to 40°C before draining.
[][]Do not operate water bath without water.
[][]Do not open the lid during operation.
[][]Always use the lid when the instrument is not in use to avoid contaminants landing in the bath liquid.

Operation:

[][]Check the calibration sticker to ensure that the instrument is within due date of calibration.
[][]Check the water level, if required, the bath is filled to an appropriate level with purified water prior to switching it on.
[][]Switch on the bath using the ‘O/I’ switch, located at the right side of back of the shaking water bath.
[][]At first display will show “Clifton”.
[][]Press [Enter] button for Menu.
[][]To create a program, select “Do nothing” by using [UP/DOWN] key and press [Enter] button.
[][]Set the required temperature by [UP/DOWN] key and press [Enter] button.
[][]Select “Disable” by using [UP/DOWN] key and press [Enter] button.
[][]Then display will show “Stopped”.
[][]Press [Enter] button for next step.
[][]Set delay start time, ramp time by using [UP/DOWN] key and press [Enter] for next step.
[][]Set the set temperature by using [UP/DOWN] key and press [Enter] button to set the dwell time by using [UP/DOWN] key.
[][]Press [Enter] button.
[][]Select “English” by using [UP/DOWN] key and press [Enter] button for two times.
[][]Display will show a graph.
[][]Press [Enter] button for three times.
[][]Select “Start” by using [UP/DOWN] key and press [Enter] button.
[][]Select “Yes” to conform by using [UP/DOWN] key and press [Enter] button.
[][]Select “Local” by using [UP/DOWN] key and place the beaker containing sample into the shaking water bath and press [Enter] to start the instrument.
[][]LED indicator will illuminate when the bath temperature is either 4°C above or below set temperature.
[][]After completion of work, switch off the bath using ‘O/I’ switch, located at the right side of back of the shaking water bath.

Calibration:

[][]Calibrate the Shacking water bath once in a year.
[][]Fill purified water in water bath to an appropriate level.
[][]Switch on the bath using the ‘O/I’ switch, located at the right side of back of the shaking water bath.
[][]Set the desired temperature against calibrated standard thermometer at 37⁰C, 50⁰C, 90⁰C.
[][]Allow 30 minutes to equilibrate.
[][]Check the temperature using a calibrated standard thermometer and record the temperature in the calibration information sheet for shaking water bath (as per Annexure-I).

Cleaning:

[][]Clean the instrument once in a week or in between when water becomes dirty.
[][]Switch ‘OFF’ the instrument.
[][]Open the lid of the shaking water bath.
[][]Wash the lid properly with purified water.
[][]Remove the water from water bath to reduce potential biological contamination.
[][]Wash the shaking water bath with soapy water and then purified water.
[][]Mop with clean dry cotton cloth.
[][]Use 10% nitric acid on a cloth (wear suitable gloves) to remove any deposits.
[][]Add 1 litre of vinegar to water in the stainless steel tank, gently heat to 50°C for an hour, empty and brush the lime away for descaling. Rinse thoroughly afterwards.
[][]Fill with purified water up to desired level of the shaking water bath.
[][]Close the lid of bath.

Annexure:

Annexure-I: Calibration Information Sheet for Shaking Water Bath.

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Calibration of Polarimeter With Operation, and Cleaning

Calibration of Polarimeter , Purpose :

Calibration of Polarimeter , The purpose of this SOP is to describe the operation, calibration and cleaning of Polarimeter (Model: Rudolph, AUTOPOL IV) used for the determination of the optical rotation in quality control laboratory at XX Pharmaceuticals Ltd.

Calibration of Polarimeter , Scope :

This procedure describes the application of Polarimetric determinations of optical rotation of raw materials (active & excipients), intermediates and drug product etc. in the quality control laboratory of general block at XX Pharmaceuticals Limited.

Definitions/Abbreviation:

Standard Operating Procedure (SOP): A written authorized procedure, which gives instructions for performing operations.

Responsibilities:

The roles and responsibility is as follows:

Officer/Executive/ Sr. Executive, Quality Control

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]Arrange training on the SOP to all concerned personnel.
[][]To ensure implementation of the SOP after training.
[][]Schedule calibration of the instrument at the defined intervals.

Head of Quality Assurance

[][]Approval of the SOP.
[][]To ensure overall implementation of this SOP.

Procedure:

Precaution(s):

[][]The equipment should not be set near to room heating equipment or direct sunlight.
[][]Not to spill water or sample on the main body of the instrument.
[][]Use the instrument at an ambient temperature of 5°C to 35°C and RH lower than 90%.
[][]Disconnect the power supply before moving or cleaning of the instrument.

General procedure:

Polarimetry is used to measure the effect that an optically active molecule in solution has on polarized light. Specific Optical Rotation is defined as an Observed Optical Rotation, measured at a specific wavelength and temperature, corrected for the path length of the optical cell and concentration of the solution. The sample is normally presented to the Polarimeter as a solution, contained in a thermally controlled optical cell. A beam of polarised light is then passed through this cell and any rotation of this polarised light is measured via a detector

Reagent quality:

[][]If water is used in the preparation of sample solutions, it must be purified by distillation or deionization process.

Instrument equilibration:

[][]The instrument must be equilibrated before use. The polarimeter (set to required wavelength), must be switched on for a minimum of at least 30 minutes before use.

Preparation and storage of samples:

[][]Sample solutions must be prepared in accordance with the analytical method. Sample solutions must be discarded at the end of the working day, unless solution stability has been demonstrated.

Preparation for measurement:

[][]Connect the power cable and turn the Polarimeter ON.
[][]Press Menu to select the measurement settings.
[][]Press Scale button and select the specific optical rotation.
[][]Press Temperature correction and select off mode.
[][]Press Statistics button and select on (n-1).
[][]Exit from the Menu by pressing Exit button.
[][]Fill the Polarimeter cell with sample blank and place it into the sample chamber.
[][]Press Zero button for zeroing the sample blank.
[][]Then remove the cell from the sample chamber and discard the sample blank and rinse the cell with the sample.
[][]Fill the cell with the sample and press Measure.
[][]Type the Lot ID and press Enter.
[][]Input the sample weight and press Enter.
[][]Type the Sample Name again presses Enter.
[][]When the measurement completed, press Print Option to the results.
[][]Remove the polarimeter cell from the chamber.

Calculation of Specific Optical Rotation:
The specific optical rotation of a sample is calculated as follows:

A=αx100/I x c

Where,
[α] = Specific Rotation at Temperature, T°C and wavelength, λ nm
Α = Observed Rotation in degrees (°)
l = Path length in decimeters (dm)
c = Concentration of analyte (g /100 ml)

Cleaning of the instrument:

Cleaning of the cell:

[][]The cell must be cleaned after use. Thoroughly rinse the cell with the same solvent used for the sample, then rinse with purified water followed by methanol.

Cleaning of the sample compartment:

[][]The sample compartment should be cleaned immediately if anything is spilled into it in order to preserve the black matt finish and prevent corrosion or contamination.
[][]Use a soft cloth impregnated with a soapy solution to rub away any foreign material.
[][]Use a clean soft cloth dampened with water to rinse the cleaned surfaces thoroughly.
[][]Finally dry with a lint free cloth or tissue.

Calibration check with sucrose solution:

[][]Frequency: Yearly
[][]The check consists of determining the specific optical rotation of sucrose solution, using 20% w/v solutions. The method is detailed below. All results and calculations must be recorded on the calibration information sheet for Polarimeter.

Procedure:

Apparatus:

1dm Polarimeter tube.
Thermostat bath 20°C ± 0.2°C.

Reagent:

Sucrose Solution

Loss on Drying:

[][]Accurately weigh approximately 1g of sucrose into a clean dry weighing bottle that has previously been dried at 105°C, cooled in a dessicator for half an hour and weighed.
Dry in an oven at 105°C±2°C for 2 hours, then cool in a desiccator and reweigh.
[][]Calculate the loss in weight as a percentage and record the result on the polarimeter calibration check sheet using the following calculation:

LOD=Weight loss(g)/Weight taken(g)x100

Determination of Specific Optical Rotation at 20°C:

[][]Accurately weigh about 20 g of Sucrose into three separate 100 ml volumetric flasks. Dissolve in 80 ml of water and dilute to 100 ml with water.
[][]Zero the polarimeter using purified water in the 1dm polarimeter tube.
[][]Determine the optical rotation of each solution at 20°C ± 0.5°C in the 1dm tube.
[][]Record and calculate the results obtained for each solution on the polarimeter calibration check sheet using the following calculation:

A=αx100x100/I x c x(100-%LOD)

Where,
[α] = Specific Rotation at Temperature, 20°C and wavelength, 589.3 nm
A = Observed Rotation in degrees (°)
l = Path length in decimeters (dm)
c = Concentration of analyte (g/100 ml)
The specific optical rotation for each solution should be in the range +66.3° to +67.0° (reference the current European Pharmacopoeia).

Calibration check with Quartz Control Plate:

Frequency: Yearly
Apparatus:
Quartz Control Plate
[][]Check that the instrument and the Quartz Control Plate are at room temperature and that the instrument has been on for at least 10 minutes with the Quartz control Plate resting in the back of the sample chamber.
[][]Press Menu button to select Measurement Settings.
[][]Press Scale to select Optical Rotation.
[][]Press Temperature Correction and select Quartz.
[][]Press Statistics and select on (n-1).
[][]Press Exit button to return Manu.
[][]Press zero for zeroing the instrument.
[][]Place the Quartz Control Plate in to the sample chamber.
[][]Press Measure to measure the Quartz Control Plate.
[][]Type the Lot ID and press Enter.
[][]Type the Sample ID and press the Enter.
[][]Type the Sample Name and press the Enter.
[][]When the measurement completed press Print/Send key to print the measurement results.
[][]Remove the Quartz Control Plate form the chamber and return it to its container.
[][]Review the measurement results. Verify the Quartz Control Plate measure is within the tolerance specification.

Annexure:

[][]Annexure-I: Calibration Information Sheet for Polarimeter with Sucrose Solution
[][]Annexure-II: Calibration Information Sheet for Polarimeter with Quartz Control Plate
[][]Annexure-III: Log Book for Polarimeter

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Water Purification System Operation

Water Purification System, Purpose :

Water Purification System, This purpose of this SOP is to describe the operation of Water Purification System (Model: Barnstead Easy Pure II 7136).

Water Purification System, Scope :

This procedure is applicable for Water Purification System (Model: Barnstead Easy Pure II 7136), installed in the quality control laboratory  of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure
[][]QC: Quality Control

Responsibilities:

The roles and responsibility is as follows:

Executive/ Sr. Executive, QC

[][]Ensure that the instructions of this procedure are correctly followed

Manager, Quality Control

[][]Ensure that this procedure is kept up to date.
[][]Ensure appropriate personnel from the section are trained on this procedure.
[][]Ensure the instrument safety information is maintained as per manual.
[][]Ensure that the water system is ready for use.
[][]Ensure that the water system is sanitized properly at due time.
[][]Confirm that SOP is technically sound and reflects the required working practices.

Head of Quality Assurance

[][]Approval of the SOP
[][]To ensure the overall implementation of the SOP.

Annexure:

N/A

Procedure:

General precaution:

[][]Use a properly grounded electrical outlet of correct voltage and current handling capacity.
[][]Do not locate your EASY pure II directly over equipment that requires electrical service. Routine maintenance of this unit may involve water spillage and subsequent electrical shock hazard, if improperly located.
[][]Replace fuses only with the same type and rating of fuse.
[][]Do not assemble water lines or remove cartridges where spilled water could contact equipment that requires electrical service. Electrical shock could result.
[][]Disconnect from the power supply prior to maintenance and servicing.
[][]Does not use in the presence of flammable or combustible materials; fire or explosion may result. This device contains components which may ignite such materials.
[][]Do not use in the presence of highly corrosive substances such as bleach or acid baths; fire may result.
[][]This device is to be used with water feeds only. Cleaning agents must be used in compliance with instructions in this manual. Failure to comply could result in explosion and personal injury.
[][]Avoid splashing cleaning solutions on clothing or skin.
[][]Ensure all piping connections are tight to avoid chemical leakage.
[][]Ensure adequate ventilation.
[][]Carefully follow manufacturer’s safety instructions on labels of chemical containers and material safety data sheets.
[][]Depressurize system prior to opening cartridge access door or removing top cover.
[][]This unit may be equipped with an ultraviolet lamp. Ultraviolet radiation is harmful to the eyes and skin. Do not observe the lamp directly.

Operation:

[][]Turn main power on at power entry module.
[][]Switch on the Water Purification System located on the upper left side of the instrument.
[][]The Barnstead EASY pure II 7136 control panel incorporates three switches ‘STOP’,’STAND BY’, ‘START’ and a digital display.
[][]Connect the instrument with purified water supply by feed water tubing.
[][]Pressing the ‘START’ when the unit is in either the stop or standby mode will put the instrument into Run Mode.
[][]When the display will show the resistivity 18.2 MΩ-cm at 25°C, the water can be taken from the instrument for different purposes by pushing down the Draw-off Valve Lever.
[][]To reserve the RO water for further use, connect the Water purification system with Barnstead 30 liter Storage reservoir with water inlet tubing.
[][]Push down the Draw-off Valve Lever to transfer the RO water from Water purification system to Barnstead 30 liter Storage reservoir by water inlet tubing.
[][]Use the water from the Barnstead 30 liter Storage reservoir for different purposes by Draw Off Valve.
[][]Use Product water outlet to drain the RO water if necessary.
[][]Finally power off Water Purification System.
[][]Unplug the instrument from the main power connection.

Water Purification System Operation Read More »

Temperature Monitoring of Refrigerator with Operation, & Cleaning

Temperature Monitoring of Refrigerator, Purpose :

Temperature Monitoring of Refrigerator, This purpose of this SOP is to describe the operation of Refrigerator for preservation of reference standard and others temperature sensitive materials in Quality Control Laboratory and Microbiology Laboratory.

Temperature Monitoring of Refrigerator, Scope :

This procedure is applicable for the preservation of reference standard and others temperature sensitive materials into Refrigerator in Quality Control Laboratory and Microbiology Laboratory of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure
[][]QC: Quality Control

Responsibilities:

The roles and responsibility is as follows:

Executive, QC

[][]Ensure that the instructions of this procedure are correctly followed.

Manager, Quality Control

[][]Ensure that this procedure is kept up to date.
[][]Ensure that the materials are preserved at defined temperature.
[][]Ensure appropriate personnel from the section are trained on this procedure.
[][]Confirm that SOP is technically sound and reflects the required working practices.

Head of Quality Assurance

[][]To ensure the overall implementation of the SOP.
[][]Approval of the SOP.

Procedure:

Precaution(s):

[][]Do not store articles on the top of the refrigerator.
[][]Do not put a container filled with water on the refrigerator. If spilled, there is a risk of fire or electric shock.
[][]Do not insert your hands into the bottom area under the refrigerator.
[][]Do not overfill the refrigerator with the material.
[][]Do not touch the inside walls of the freezer or products stored in the freezer with wet hands.
[][]Never put fingers or other objects into the water dispenser hole, ice chute and ice maker bucket.
[][]Do not spray inflammable gas near the refrigerator.
[][]Do not store volatile or flammable substances in the refrigerator.
[][]Do not reset the temperature without approval.

Operation:

[][]Connect and switch on the power of Refrigerator.
[][]Set the temperature within 2-8°C.
[][]After stable of the temperature, keep the items into the chamber at specific area.
[][]Check that the chamber temperature is within the setting value by standard calibrated thermometer.
[][]Record the temperature in Temperature log sheet for refrigerator (Annexure-I).
[][]Read the label of the materials to confirm the storage temperature.
[][]Store materials in refrigerator as per label.
[][]Minimize the door opening and closing to protect the chamber temperature increasing.

Cleaning procedure:

[][]Clean the inside walls and accessories with a mild detergent and then wipe dry with a soft cloth.
[][]Wipe the digital panel and display panel with a clean, soft cloth.
[][]Spray water onto the cleaning cloth instead of spraying directly on the outer surface of the refrigerator.
[][]The doors, handles and cabinet surfaces should be cleaned with a mild detergent and then wiped dry with a soft cloth.
[][]Keep the door seals free of grit or grime by cleaning the doors with a mild detergent and damp cloth then wipe with dry, clean and soft cloth.

Maintenance:

[][]If Refrigerator shows any mechanical, electrical or any others problem, inform to the supplier or Engineering Department for maintenance.

Annexure:

Annexure-I: Temperature Log Sheet for Refrigerator.

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Maintenance of emergency shower and eye/ face wash With operation

Maintenance of emergency shower, Purpose:

Maintenance of emergency shower, The purpose of this SOP is to describe the operation and maintenance of Emergency Shower and Eye/Face wash in Quality Control Laboratory.

Maintenance of emergency shower, Scope:

This procedure is applicable for Emergency Shower and Eye/ Face wash used in Quality Control Laboratory of general block of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

N/A

Responsibilities:

The roles and responsibility is as follows:

Executive, QC

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.

Head of Quality Assurance

[][]Approval of the SOP.
[][]To ensure the overall implementation of the SOP.

Annexure:

N/A

Operating Procedure:

Performance Checking:

[][]Check the unit performance once in a year.
[][]Turn the valve on to full open position (activation of the unit). The eyewash nozzles shall have a dust protecting cover, which shall be automatically removed upon activation of the unit.
[][]Ensure that the water flow of the unit at least 1.5 Liters/minute.
[][]Check that the unit shall deliver flushing fluid to both eyes simultaneously at a velocity low enough to be non-injurious to the user.
[][]Check that the flushing fluid temperature shall be normal. Temperature in the range of 20-30°C (about 80-95°F) is considered suitable.
[][]Check the Push or Pull valve shall not take more than 1 second to start the water flow

Eye/ Face washing:

[][]Position the eye or face on the shower.
[][]Pull “ROD” valve to open the water flow immediately.
[][]Rinse the effected eye with abundant water to remove any residual portion form the eye.
[][]After flushing, push “ROD” valve to stop the water flow.
[][]Keep the unit stand by position for the next use

Emergency Showering:

[][]Position the body under the unit.
[][]Expose the specific infected portion or whole body (if injured the whole body) exactly near “Shower Head”
[][]Pull “ROD” valve to open the water flow immediately.
[][]Open the valve to the full position.
[][]Flush with the sufficient water to the injured part or whole body until the chemical residue is removed.
[][]After flushing, push “ROD” valve to stop the water flow.
[][]Keep the unit stand by position for the next use.

Maintenance:

If Shower and Eyewash shows any mechanical, electrical or any others problem, inform to the supplier or Engineering Department for maintenance.

Maintenance of emergency shower and eye/ face wash With operation Read More »

Vacuum Drying Oven Calibration With Operation & Cleaning

Vacuum Drying Oven Calibration, Purpose :

Vacuum Drying Oven Calibration, The purpose of this SOP is to describe the operation, calibration and cleaning of Vacuum Drying Oven (Model: VO 200S) used for drying of the raw materials in the quality control laboratory at XX Pharmaceuticals Ltd.

Scope :

Vacuum Drying Oven Calibration, This procedure is applicable for the Vacuum Drying Oven, installed in the quality control laboratory for general block at XX Pharmaceuticals Limited.

Definitions/Abbreviation:

[][]QC: Quality Control

Responsibilities:

The roles and responsibility is as follows:

Officer/Executive/Sr. Executive, Quality Control

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]Arrange training on the SOP to all concerned personnel.
[][]To ensure implementation of the SOP after training.
[][]Schedule calibration of the instrument at the defined intervals.

Head of Quality Assurance

[][]Approval of the SOP.
[][]To ensure overall implementation of the SOP.

Annexure:

[][]Annexure-I : Log Book for Vacuum Drying Oven
[][]Annexure-II: Calibration Record of Vacuum Drying Oven

Procedure:

Precaution(s):

[][]Wear the temperature resistance gloves to keep or remove materials from Vacuum Drying Oven.

Operation:

[][]Operation in normal mode
[][]Switch on the main switch of the Vacuum Drying Oven.
[][]Open the door and place the samples into the Vacuum Drying Oven.
[][]Press push/turn control key to put on the main power switch in front of the Vacuum Drying Oven. The Vacuum drying oven will start in normal mode with the display of timer, the chamber temperature, alarm temperature (red color indication).
[][]Select operating mode “Normal operation”. Press and hold on the SET key (approx. 3 sec) until the current operating option is flashing.
[][]Select temperature set point. Hold down the SET key and use the push/turn control key clockwise or anticlockwise to select the required temperature set point.
[][]After the SET key has been released the Vacuum drying oven briefly flashes the temperature set point. Set the temperature as per requirement. Heating is indicated by the orange heater symbol.
[][]Select the fan speed. Turn the push/turn control clockwise until the fan symbol is flashing. While the holding down the SET key. Use the push/turn control to set 50% fan speed.
[][]Select the alarm temperature. Turn the push/turn control clockwise until the monitor temperature display is flashing. Hold down the SET key and use the push/turn control to set the alarm temperature.
[][][][]The display then changes to the actual current temperature and starts to the setting temperature. The temperature will be automatically increased at setting temperature and display the setting temperature digitally.
[][]Observe the display temperature until stable position.
[][]At the end of drying, remove dried materials from Vacuum drying oven.

Operation in cyclic mode :

[][]Press push/turn control key to put on the main power switch in front of the instrument. The Vacuum drying oven will start in normal mode with the display of timer, the chamber temperature and alarm temperature (red color indication).
[][]Hold down SET key and turn the push/turn control key at the clockwise or anti clockwise for setting date, local time, operating temperature, alarm temperature. After setting, SET key will be released the display briefly flashes the set point.
[][]Press and hold down SET key to select the program and rotate push/turn control key at clockwise and select “Ramp timer” mode.
[][]Hold down the SET key and set the work day’s group using the push/turn control. Press push/turn control to select the ramp segment “t1” If the day is not required, it will be off position.
[][]Hold down the SET key and set the time using push/turn control.
[][]Select the ramp segment “t2” using the push/turn control. Hold down the SET key and using the push/turn control set the time.
[][]Turn push/turn control clockwise until the temperature display is flashing. Hold down the SET key and set the required temperature set point using push/turn control.
[][]Select the set point waiting time. Hold down the SET key and set on using the push/turn control. After the SET key has been released the function for set point waiting time is stored.
[][]Select hold time “t3”. Hold down the SET key and set the time using the push/turn control.
[][]Select the cooling time “t4”. Hold down the SET key and set time using push/turn control.
[][]Select program repeats “loop”. Hold down the SET key and set 2 for repeats using the push/turn control.
[][]Select the fan speed to set the air changes. Turn the push/turn control clockwise until the fan
[][]symbol is flashing. Hold down the SET key and set fan speed 50% suing the push/turn control.
[][]Select the alarm temperature. Turn the push/turn control clockwise until the monitor temperature display is flashing. Hold down the SET key and set the alarm temperature using the push/turn control.
[][]Turn the push/turn control at clockwise until the fan symbol flashing to move the air slider opens and closes the air valve to control the supply and discharge of air.
[][]Start the program. Turn the push/turn control clockwise until the stop symbol ▀ is flashing. Hold down the SET key and select start ► using the push/turn control. On releasing the SET key the program
starts to run.

Vacuum pump operation:

[][]After setting the drying temperature, switch on the vacuum pump.
[][]After completion of vacuum drying, turn the push/turn control knob until the Open door option is displayed. Press SET key to release the vacuum. Switch off the vacuum pump. Then the door of Vacuum drying oven can be opened.

Calibration:

[][]Frequency: Perform calibration of the instrument once in a year or if the system has been moved, serviced or a malfunction is suspected.

Temperature Calibration

[][]Insert the standard thermometer or thermocouples into the chamber.
[][]Press and hold down SET key until the normal mode light blinking.
[][]Turn push/turn control key clock wise to reach SETUP light.
[][]Select Calibration to rotate push/turn control key.
[][]Use three calibration temperatures as below :
CAL.1 : 30°C
CAL.2 : 100°C
CAL.3 : 200°C
[][]Select the required calibration temperature in SETUP key and set the corresponding calibration correction to 0.0°C.
[][]Measure the deviation from the selected calibration temperature under the steady conditions, using a reference instrument.
[][]Set the calibration correction in SETUP key. If the measured reference temperature is too low, the calibration correction setting is negative sign.
[][]Adjust the temperature if require from adjusting value of calibration temperature (CAL). The correction value should not more than ±0.50C.
[][]Carry out the check measurement using the reference thermometer.
[][]Carry out others two calibration temperatures in the same manner.
[][]Measure the vacuum pressure and input the data on calibration record.
[][]In case of internal calibration, record calibration data in Vacuum drying Oven Calibration Record, as per Annexure-II.

Calibration of pressure for vacuum chamber

[][]Calibrate pressure of vacuum chamber by calibrated multi-functional calibrator using five calibration pressures as below :
CAL.1 : 10 mbar
CAL.2 : 50 mbar
CAL.3 : 100 mbar
CAL.4 : 500 mbar
CAL.5 : 900 mbar
[][]Record calibration data in Vacuum drying Oven Calibration Record, as per Annexure-II.
[][]Cleaning of Vacuum Drying Oven :
[][]Clean the inner part of Vacuum drying oven with a cleaned cloth.
[][]Disinfect the inner surfaces with 70% IPA or ethanol when required.
[][]Clean the outer surfaces with dry cleaned cloth.

Maintenance :

[][]If Vacuum drying oven shows any mechanical, electrical or any others problem, inform to supplier or Engineering Department for maintenance.
[][]After maintenance, recalibrate the Vacuum drying oven.

Vacuum Drying Oven Calibration With Operation & Cleaning Read More »

Muffle furnace operation, cleaning and maintenance

Muffle furnace, Purpose :

Muffle furnace, The purpose of this SOP (Standard Operating procedure) is to describe the operation and maintenance of Muffle furnace for the determination of Ash, Sulphated ash/residue on ignition and Loss on ignition and other tests (which required higher temperatures and furnace) of the materials under specified condition.

Muffle furnace, Scope :

This procedure is applicable for Muffle furnace (Model: Carbolite, CWF1200), installed in the quality control laboratory for general block of  XX  Pharmaceuticals Limited.

Definitions:

SOP: Standard Operating Procedure.
QC: Quality Control.

Responsibilities:

The roles and responsibility is as follows:

Executive, QC

[][]To ensure that the instructions of this procedure are correctly followed.
[][]To ensure cleaning of Muffle Furnace safety rules.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.

Head of Quality Assurance

[][]To ensure the overall implementation of the SOP.
[][]Approval of the SOP.

Procedure:

Precaution(s):

[][]Do not open the door during operation of Muffle Furnace.
[][]Always wear vinyl/heat resistance gloves to put and to remove the crucible from the furnace using the long tongs.
[][]Ensure that heating elements are isolated from the door and the inner surface of the chamber.

Operation:

[][]Connect the instrument to the main power supply.
[][]Switch ‘ON’ the mains.
[][]Press “■” key button.
[][]Display will show SPºC.
[][]Use “▲” up or “▼” down arrow key button to set the required temperature.
[][]Press “■” key button.
[][]Then display will show SPrr.
[][]Use “▲” up or “▼” down arrow key button to set ram temperature.
[][]Press “■” key button.
[][]Display will show t S.
[][]Use “▲” up or “▼” down arrow key button to set the time (Hr:Min) by a single press.
[][]Machine will automatically increase the temperature according to ramp temperature.
[][]After reach the set temperature, machine will hold that temperature according to set time.
[][]Then display will show ‘End’.
[][]Switch OFF the instrument and mains.

Cleaning procedure:

[][]Insure that main power switch of the equipment is “OFF” position and at room temperature.
[][]Clean the outer surface of the furnace with a damp cloth.
[][]Clean the inner surfaces with dry cleaned cloth or soft nylon brush.

Maintenance:

[][]If Muffle furnace shows any mechanical, electrical or any others problem, inform to supplier or
[][]Engineering Department for maintenance.

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Calibration of Digital Hygrometer with operation, and maintenance

Calibration of Digital Hygrometer, Purpose :

Calibration of Digital Hygrometer, This purpose of this SOP is to describe to operate of Hygrometer for the determination of temperature and humidity of Quality Control Laboratory, Microbiology Laboratory, and Product Development.

Calibration of Digital Hygrometer, Scope :

This procedure is applicable for the determination of room temperature and humidity by digital hygrometer used in Quality Control Laboratory, Microbiology Laboratory, and Product Development of  XXP Pharmaceuticals Ltd.

Definitions/Abbreviation:

N/A

Responsibilities:

The roles and responsibility is as follows

Officer/Executive/Sr. Executive, Quality Control

To ensure that the instructions of this procedure are correctly followed

Manager, Quality Control

[][]To ensure that SOP is kept up to date.
[][]To ensure appropriate personnel from the section are trained on this procedure.
[][]To confirm that the SOP is technically sound and reflects the required working practices.

Head of Quality Assurance

[][]To ensure the overall implementation of the SOP.
[][]Approval of SOP

Procedure:

Precaution(s):

[][]Keep the sensor’s protective cap closed to extend the sensor’s life when the meter is not in use.
[][]Do not use for cleaning abrasive or solvents on these instruments.
[][]Do not store or use the meter outside the operating/storage environment.
[][]Allow time to stabilize the meter, when moving from one temperature/humidity extreme to other.

Operation:

[][]Check the calibration sticker to ensure that the instrument is within due date of calibration.
[][]Remove the RH sensor protective cap before use.
[][]Press Power button to turn the meter on.
[][]Setting Time-of-Day:
[][]Slid the CLOCK SET switch, located on the back of the unit to the CLOCK SET position
[][]Press HR and MIN button to set the hours and minutes respectively;
[][]Press and hold the button to rapidly advance the display.
[][]Setting 12/24 Hour Display:

[][]Slide the 12HR/24HR switch, located on the back of the unit to the desired position. In 12 hour format, “AM/PM” will appear on the display.
Selecting °C or °F:
[][]To display the temperature reading in Celsius or Fahrenheit, slide the °C/°F switch, located on the back of the unit, to the desired position.

Viewing the Humidity Memory:

[][]To view the humidity memory, press the HUMIDITY MEMORY button. The maximum humidity reading achieved will be displayed (“MAX” will appear on the display)
[][]Press the HUMIDITY MEMORY button a second time, within 10 seconds, to view the minimum humidity achieved (“MIN” will appear on the display)
[][]Press the HUMIDITY MEMORY button a third time, within 10 seconds, to return the current reading.

Clearing the humidity memory:

The maximum and minimum humidity memory may be cleared individually. To clear the desired humidity memory (MIN or MAX), press the CLEAR button while the memory value is being displayed (follow 7.1.7 to view the Humidity Memory)

Viewing the Temperature Memory:

[][]To view the temperature memory, press the TEM MEMORY button. The maximum temperature reading achieved will be displayed in the middle display (“MAX” will appear to the right of the value);
[][]The minimum temperature reading achieved will be displayed in the top display (“MIN” will appear to the right of the value);
[][]Press the TEM MEMORY button a second time, within 5 seconds, to return the current temperature and time-of-day display.

Clearing the humidity memory:

[][]To clear the temperature memory (MIN and MAX), press the CLEAR button while the memory value is being displayed (follow 7.1.9 to view the temperature Memory)
[][]Use annexure-I for recording of temperature and relative humidity, and use annexure-II for recording of temperature only as per requirements.

Calibration Procedure:

[][]Check the temperature and humidity using a digital thermo hygrometer and record the temperature and humidity in the calibration certificate. as per Annexure-V of Engineering.

[][]Calibrate the digital hygrometer once in a year ± 15 days.

Maintenance:

[][]If Humidity meter shows any mechanical, electrical or any others problem, inform to the supplier or
Engineering Department for maintenance.

Annexure

Annexure-I : Temperature and Humidity Record Sheet
Annexure-II : Temperature Record Sheet

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Calibration of Potentiometric Titrator with Operation & Cleaning

Calibration of Potentiometric Titrator, Purpose :

Calibration of Potentiometric Titrator, The purpose of this SOP is to define the current procedure for the operation, calibration and cleaning of Potentiometric Titrate (Mettler-Toledo, Model: T50) within Analytical laboratory at XX  Pharmaceuticals Ltd.

Calibration of Potentiometric Titrator, Scope :

This procedure is applicable to the determination of the potency and/or purity of raw materials (Active & Excipients), intermediates and drug product etc. in the quality control laboratory of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A

Responsibilities:

The roles and responsibility is as follows:

Executive, QC

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Manager, Quality Control

[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]Arrange training on the SOP to all concerned personnel.
[][]To ensure implementation of the SOP after training.
[][]Maintaining calibration schedule of the instrument at the defined intervals.

Head Quality Assurance

[][]Approval of the SOP.
[][]To ensure overall implementation of the SOP.

Procedure:

Precaution(s):

[][]Laboratory coat, safety glasses and must be worn while handling the instrument.
[][]Ensure that the main switch and power supply connector are accessible during use.
[][]There is a chance of liquid spillage at high speed. Always gradually increase the speed to the desired level.
[][]Remove the plug from the main socket during cleaning.

General procedure:

[][]Titration is a technique for determining the potency and/or purity of synthetic raw materials, intermediates, drug substances, excipients and drug products, and for standardizing volumetric solutions. Although less specific than chromatographic techniques it is useful for quality control purposes where more details impurity quantization is not requested. Titration for assay of active substances is frequently used in pharmacopoeia monographs for drug substance and drug product.

[][]Samples are quantified by reaction in solution with a volumetric solution of known strength. A graduated glass tube fifed with a stopcock and fine tip is used to deliver deliver variable amounts of titrant, accurately measured, until the point at which the stoichiometric analytical reaction is complete. The endpoint may be determined use of color indicators or electrochemically. Where electrochemically endpoint detection is employed, automated burettes and endpoint detection may be used.

Automatic Burettes:

[][]This type of burette is found on automatic titration and dilution equipment. These devices are capable of very high precision volumetric measurements.

Automatic Titrates:

[][]Two types of automatic titrates are recorded the electrode potential differences during the course of titration as the expected sigmoid curve. This type is recommended for purchase and use since it offers greater accuracy and precision. In the second type, titrant addition is performed automatically until a pressed potential or pH, representing the endpoint, is reached, at which point the titrant addition ceases.

Indicator electrode:

[][]Choice of indicator electrode depends on the substance being examined and be a glass or metal electrode. The reference electrode is generally a calomel or silver-silver chloride electrode. Ensure that electrodes are in good condition. Electrode for non-aqueous titration must be dedicated and not utilized for any aqueous titration techniques.

Overview of titration chemistries:

[][]Titrimetric analyses utilize one of four basic chemistries, Reduction-oxidation, Complex metric, Precipitation and Acid-base, which may also be subdivided into non-aqueous and aqueous titrations.

Operations:

Manual Operation:

Enter the following parameters
[][]Stirrer
[][]Sensor
Temperature sensor
Potentiometric sensor
Polarized sensor
Conductivity sensor
[][]Burette
Rinse burette
Rinsing several burette at the same time
Dispense
Manual titration
[][]Pump
[][]Auxiliary instrument
[][]Sample Changer

You can determine the following parameters:

[][]Press ‘Manual’ to select Parameters.
[][]To ’Set’ parameters and input data. You would like to use and adjust the parameters.
[][]Press “Start’ to start the parameters procedure.
[][]You can select ‘Stop’ to terminate the procedure at any time.
[][]Press ‘Exit’ to end the manual operation.
[][]Press ‘Home’ and retune to main menu.

Methods:

Loops:

[][]There are the following loop types.
[][]A sample loop is for analyzing a sample.
[][]A calibration loop is for calibrating a sensor.
[][]A titer is for determining the titer of a titrate.

Types of Methods

[][]GT: Method for general titration (contains only sample loops or mixed loops).
[][]Calibration: Method for sensor calibration (contains only calibration loops).
[][]Titer: Method for titer determination(contains only titer loops)
Create a new method for general Titrant:
[][]Press ‘Method’
[][]Choose ‘New’ to create a new method on the basis of a template.
[][]From the available templates, choose method template EP by pressing ( ).Then press ok and exit.
You can modify this method in line with your requirements by inserting removing method functions or modify its parameters.
[][]Press ‘Title’ method function, enter a new method ID. After wards, a new method will be stored under this Method ID. Press ok and exit.
[][]Assign a ‘title’ to your new method.
[][]Press Sample button and input Sample ID, Entry Type, Density, Correction factor, Temperature and Entry in line with your requirements. Press ok and exit.
[][]Press Titrant Stand button and select manual stand. Press ok and exit.
[][]Press stirrer button and select stirrer speed and duration. Press ok and exit.
[][]Press Titration [EQP] [1].Press ok and exit.
[][]Input titrant and concentration by pressing titrant button.Press ok and exit.
[][]Press Sensor key and then input type, sensor and unit. Press ok and exit.
[][]Input stirrer speed by pressing stirrer. Press ok and exit.
[][]Input mode and wait time after pressing pre-dispensing key. Press ok and exit.
[][]Input Control and Mode after pressing control. Press ok and exit.
[][]Input molecular weight of the materials after pressing calculation. Press ok and exit.
[][]After inserting all required method function, you can store the new method in the titrator by choosing ‘Save’.

Annexure:

Annexure-I: Calibration Information of Potentiometric Titrator.
Annexure-II: Log Book for Potentiometric Titrator.

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Calibration of centrifuge machine with operation, and cleaning

Calibration of centrifuge machine, Purpose :

Calibration of centrifuge machine, The purpose of this SOP is to describe the operation, calibration and cleaning of Centrifuge Machine (Model: Thermo Scientific Heraeus, Biofuge Primo), used to get supernatant from a suspension using centrifugal force.

Calibration of centrifuge machine, Scope :

This procedure is applicable for Centrifuge Machine (Model: Thermo Scientific Heraeus ,Biofuge Primo), installed in the quality control laboratory  of XX Pharmaceuticals Limited

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]QC: Quality Control.
[][]RPM: Rotations per minute

Responsibilities:

The roles and responsibility is as follows:

Sr. Executive/Executive, QC

[][]To ensure that the instructions of this procedure are correctly followed.
[][]To ensure cleaning of centrifuge machine maintaining safety rules.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.
[][]Schedule calibration of the instrument at the defined intervals.

Head of Quality Assurance

[][]Approval of the SOP
[][]To ensure the overall implementation of the SOP.

Procedure:

[][]General precautions or operational safety:
[][]Laboratory coat and safety glasses must be worn while handling the instrument.
[][]Ensure that the main switch and power supply connector are accessible during use.
[][]Remove the plug from the main socket during cleaning.
[][]Ensure use of rubber cushions for glass tubes.
[][]Balance centrifuge tubes equally.
[][]Never set the speed beyond the maximum limit.
[][]Do not operate the machine at the maximum RPM without a load.
[][]Tube materials must be compatible with solvent being used.
[][]Use only correctly fitting tubes.
[][]Never use a tube with leak or even crack.
[][]Spillage must be cleaned up immediately.
[][]Do not use centrifuge until reported faults are repaired.

Operation:

[][]Ensure the equipment is clean, calibrated and placed in a balanced surface.
[][]Switch ‘ON’ the mains.
[][]Switch ‘ON’ the instrument at the back of side. The switch lamp will be illuminated.
[][]Open the upper lid by releasing the lock using ‘ ‘ key and lifting it up.
[][]Prepare the samples and transfer the solution to the centrifuge tubes having similar size.
[][]Fill the solution in such a way that liquids in all tubes are in same level.
[][]Place the centrifuge tubes in the compartment provided for them.
[][]Place them symmetrically to the rotor axis for proper balancing at the time of rotation to prevent machine movement.
[][]Put a blank with the same liquid level for balancing, when it is required to centrifuge only one sample.
[][]Close the lid properly.
[][]Set RPM by using ‘▼▲’ key. Minimum of 300 rpm and maximum of 15000 rpm can be set.
[][]Then set Timer by using ‘▼▲’ key. The timer shows time between ‘1 min’ to ‘9 hr 59 min’.
[][]Start the instrument by pressing ‘►’ key.
[][]After completion of the centrifugation time the motor will automatically cut off and rpm will come down to 0 and the display reads “End”.
[][]If timer is not set, switch ‘OFF’ the equipment by pressing the red ‘■’ key.
[][]Open the lid by pressing ‘ ‘ key.
[][]Manually stop the centrifuge at any time by pressing red ‘■’ key.
[][]Switch ‘OFF’ the mains when not required.

Calibration:

[][]Calibrate the centrifuge machine once in a year.
[][]RPM calibration
[][]Switch ‘ON’ the mains.
[][]Switch ‘ON’ the instrument at the back of side.
[][]Set the desired RPM using RPM setting key.
[][]Check the RPM and record in the calibration information sheet for Centrifuge Machine (as per Annexure-I).
[][]Time calibration
[][]Switch ‘ON’ the mains.
[][]Switch ‘ON’ the instrument at the back of side.
[][]Set the desired time using time setting ‘▼▲’ key.
[][]Check the time using a calibrated standard timer and record the time in the calibration information sheet for Centrifuge Machine as per Annexure-I.

Cleaning procedure

[][]Clean the instrument once in a week or when required.
[][]Pull mails plug before cleaning.
[][]Clean the casing of the instrument with dry cotton cloth at first.
[][]Clean the casing, the rotor chamber, the rotor and the accessories regularly and in case of need with mild agents of pH values ranging from 6 to 8.
[][]Immediately after cleaning, dry the aluminum parts or put them into a warm-air dryer at a temperature not exceeding 50°C.
[][]After completion of each analysis, wash the centrifuge tube as per glass ware cleaning procedure

Annexure

Annexure-I: Calibration Information Sheet for Centrifuge Machine.

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Calibration of Fume Hood with operation, and cleaning

Calibration of Fume Hood, Purpose :

Calibration of Fume Hood, The purpose of this SOP is to describe the operation, calibration and cleaning of Fume Hood (Model: ESCO – EFD-4B1).

Calibration of Fume Hood, Scope :

This procedure is applicable for Fume Hood (Model: ESCO – EFD-4B1), installed in the quality control laboratory of  XX Pharmaceuticals Limited.

Definitions/Abbreviation:

[][]SOP: Standard Operating Procedure
[][]QC: Quality Control
[][]Face velocity: Face velocity is the average air flow speed at the sash opening of the fume hood into the work chamber. The measurement is expressed in m/sec or fpm.

Responsibilities:

The roles and responsibility is as follows:

Officer/Executive/Sr. Executive, Quality Control

[][]To ensure that the instructions of this procedure are correctly followed.
[][]To ensure the equipment is left clean and tidy after use.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.
[][]Schedule calibration of the instrument at the defined intervals.

Head of Quality Assurance

[][]To ensure the overall implementation of the SOP.
[][]Approval of the SOP.

Procedure:

Precaution(s):

[][]Relevant safety data sheet and safety guidelines must be followed when handling chemicals and reagents.
[][]Hazardous and fuming materials must be handled in fume hood.
[][]Wear appropriate personal protective equipment (PPE) while performing laboratory tasks in a fume hood.
[][]Keep head outside of the hood.
[][]Leave the front sash at the safe working height, when not in use.
[][]Follow laboratory procedure on the use of fume hood.
[][]Ensure the exhaust is operating before commencing work.
[][]Do not use the hood as storage area. Items can block airflow and interfere with containment.
[][]Do not leave uncapped bottles of chemicals in the hood.

Operation:

[][]Switch ‘ON’ the fluorescent lamp of the fume cupboard.
[][]Switch ‘ON’ the external exhaust blower/ fan.
[][]Lift the front sash to access in work area but not beyond the working height marked with yellow tape (30 cm).
[][]Work with the sash as fully lowered as possible, utilizing the sash as natural barrier to accidents which may occur in the hood.
[][]Plug in any electrical equipment used within the cabinet with electrical socket.
[][]Work as far into the hood as possible and with slow, deliberate movements, to minimize the external airflow disturbances.
[][]If performance is suspected, or an airflow alarm is triggered, terminate usage, close the sash completely and cease work.
[][]Report any fault regarding operation, maintenance or cleanliness of the cupboard to the supervisor.
[][]Leave the fume cupboard clean & dry after use.
[][]Turn the external exhaust blower/fan switch ‘OFF’.
[][]Turn the fluorescent lamp switch ‘OFF’.

Calibration:

[][]Calibrate the air flow (face velocity) of the fume cupboard six monthly.
[][]Switch ‘ON’ the fan.
[][]Open the window sash by sliding upward, 30 cm from the bottom.
[][]Take the reading by flow meter at left, right & middle of the fuming hood & record it in the calibration information sheet for Fume Hood (as per Annexure-I) for calculation.
[][]When instrument do not complies with the specified limits, label “Out of calibration” and get serviced.

Cleaning procedure:

[][]Clean the instrument once in a month or when required.
[][]Clean the work surface and walls with appropriate disinfectant agent and soap water.
[][]Clean the sash window using an appropriate agent disinfectant and glass cleaner.
[][]Use clean water to finish the cleaning and wash away any residue of disinfectant agent, soapy water and glass cleaner.
[][]Use a damp cloth to clean the exterior surface of the fume hood, particularly on the front and top in order to remove dust.
[][]Use Methyl-Ethyl-Ketone to remove stain or spot on the stainless steel surface as soon as possible.

Annexure:

Annexure-I: Calibration Information Sheet for Fume Hood.

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Calibration of Hot plate with Magnetic Stirrer with Operation & Cleaning

Calibration of Hot plate ,Purpose :

Calibration of Hot plate, The purpose of this SOP is to describe the operation, calibration and cleaning of Hotplate with Magnetic Stirrer (Model: Fisherbrand – FB65312).

Calibration of Hot plate, Scope :

This procedure is applicable for Hotplate with Magnetic Stirrer (Model: Fisherbrand – FB65312), installed in the quality control laboratory for general block of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]QC: Quality Control.
[][]RPM: Rotations per minute.

Responsibilities:

The roles and responsibility is as follows:

Executive, QC

[][]To ensure that the instructions of this procedure are correctly followed.
[][]To ensure cleaning of hotplate maintaining safety rules.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.
[][]Schedule calibration of the instrument at the defined intervals.

Head of Quality Assurance

[][]To ensure the overall implementation of the SOP.
[][]Approval of the SOP.

Procedure:

Precaution(s):

[][]Laboratory coat and thick rubber gloves must be worn while handling the instrument.
[][]Ensure that the main switch and power supply connector are accessible during use.
[][]Remove the plug from the main socket during cleaning.
[][]Never use sharp objects or harsh or abrasive cleaning agents when cleaning.
[][]Spillage must be cleaned up immediately after use.
[][]Do not heat beakers with any type of liquid adhering to backside.
[][]Never touch the top of the plate when the instrument is on.
[][]Never keep the heater in ‘on’ condition, when not in use.
[][]Do not use hotplate until reported faults are repaired.

Operation:

[][]Ensure the equipment is clean, calibrated and free from any dust particle.
[][]Connect the instrument to the main power supply.
[][]Switch ‘ON’ the mains.
[][]Place the beaker containing the solution in the center of the plate.
[][]For stirring option, immerse the Teflon stirring bar into the solution to be stirred.
[][]Switch ‘ON’ the instrument.
[][]Set the required stirring speed (RPM) of stirring bar by means of speed regulator knob. Turn the speed regulator knob clockwise or counter-clockwise to increase or decrease speed respectively.
[][]After stirring is over, slowly decrease the speed to zero by turn knob counter-clockwise.
[][]For heater, set the temperature by rotating the temperature setting knob to the required. It will take 5 to 10 minutes to stabilize. Turn the knob clock wise to increase the temperature or counter clock wise to decrease the temperature.
[][]After heating is over, decrease the set temperature to zero by turn knob counter-clock wise.
[][]Bright red light will flash until surface cools.
[][]After completion of work, switch ‘OFF’ the instrument.
[][]Switch ‘OFF’ the mains when not required.

Calibration:

[][]Calibrate the hotplate once in a year.
[][]Switch ‘ON’ the mains.
[][]Switch ‘ON’ the instrument.
[][]Set the desired temperature using temperature setting knob.
[][]Check the temperature using a duly calibrated thermometer and record the temperature in the calibration information sheet for hotplate with magnetic stirrer (as per Annexure-I).
[][]When instrument do not complies with the specified limits, label “Out of calibration” and get serviced.

Cleaning procedure:

[][]Switch ‘OFF’ the instrument.
[][]Switch ‘OFF’ the mains.
[][]Ensure that the surface of the plate is in room temperature.
[][]De-dust the instrument with a clean dry cloth every day.
[][]Once in a week wet mop the instrument.
[][]Wet mop using a cloth moistened in mild detergent solution and then wipe with a cloth wetted with water.
[][]Afterwards wipe the surface with a clean dry cloth to remove traces of detergent.
[][]Allow to dry the instrument before using it again.

Annexure

Calibration Information Sheet for Hotplate with Magnetic Stirrer

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Vortex Mixer Operation and Cleaning SOP

Vortex Mixer , Purpose :

Vortex Mixer , The purpose of this SOP is to describe the operation and cleaning of Vortex mixer (Model: Fisherbrand- ZX Classic), for better or error free use.

Vortex Mixer , Scope :

This procedure is applicable for Vortex mixer (Model: Fisherbrand- ZX Classic) used for mixing the solution or dissolving the various substances into solvent, installed in the quality control laboratory of XX  Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]QC: Cephalosporin Quality Control.

Responsibilities

Executive, QC

[][]To ensure that the instructions of this procedure are correctly followed.
[][]To ensure cleaning of vortex mixer maintaining safety rules.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.

Head of Quality Assurance

[][]To ensure the overall implementation of the SOP.
[][]Approval of the SOP.

Procedure:

Precaution(s):

[][]Do not press the test tube hardly on the mixing head.
[][]Do not vortex any materials for long time.
[][]Maintain the level of test solution into test tube/Vial/test flask to avoid overflow during vortex.
[][]Set the speed control to the minimum, before turning on the mixer.
[][]Disconnect vortex mixer from power source before attempting any cleaning or maintenance procedures.
[][]Never operate without a shaking head securely attached.
[][]Always wear eye protector during use of vortex mixer.
[][]Always have lids on the tubes when solvents and flammables are used on the mixer.
[][]Shake hazardous samples in appropriate containment vessels.
[][]Replace rubber attachments with new ones when these show progressive signs of wear out.
[][]Do not immerse the unit or pour liquids over it as electrical shock may occur.

Operation:

[][]Switch ‘ON’ the mains.
[][]The yellow light will be illuminated.
[][]Use the ‘continuous’ key to select the automatic vortex or manual vortex.
[][]Set the desired speed with the help of the ‘control’ knob.
[][]In case of automatic vortex option, touch test tube/vial on the mixing head to start the vortex automatically.
[][]For manual vortex, place the test tube on the mixing head and then press ‘continuous’ button.
[][]Adjust the vortex speed by turning ‘control’ knob clockwise to increase speed or anti-clockwise to decrease speed.
[][]Vary the speed and/or the angle of contact and pressure against the mixing attachment to achieve the desired mix.
[][]On completion, turn the ‘control’ knob anticlockwise to the minimum.
[][]Remove the test tube at the end of vortex.
[][]Stop the vortex by press ‘continuous’ button.
[][]Switch ‘OFF’ the mains.

Cleaning procedure:

[][]Switch ‘OFF’ the mains and disconnect the power plug.
[][]After each use, wipe down the mixer with a soft, dry cloth.
[][]Keep the unit clean by immediately blotting any spills. Remove the shaking head, if required. Clean the head with mild detergent. Dry thoroughly, before replacing the head on the unit.
[][]Clean the outer surface of the instrument properly with a non-abrasive cloth or sponge, moistened in mild detergent water, once in a week or when required.
[][]Never use harsh or abrasive cleaning agents.
[][]Allow to dry before use it again.

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Calibration of orbital shaker with operation & cleaning

Calibration of orbital shaker, Purpose :

Calibration of orbital shaker, The purpose of this SOP is to describe the operation, calibration and cleaning of Orbital Shaker (Model: Stuart SSL1), used for shaking flask, bottle and beaker to dissolve solids in liquid.

Calibration of orbital shaker, Scope :

This procedure is applicable for Orbital Shaker (Model: Stuart SSL1), installed in the quality control laboratory XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]QC: Cephalosporin Quality Control.
[][]RPM: Rotations per minute.

Responsibilities:

Executive, QC

[][]To ensure that the instructions of this procedure are correctly followed.
[][]To maintain the records properly as per SOP.
[][]To ensure cleaning of orbital shaker maintaining safety rules.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.

Procedure:

Precaution(s):

[][]Laboratory coat and safety glasses must be worn while handling the instrument.
[][]Ensure that the main switch and power supply connector are accessible during use.
[][]There is a chance of liquid spillage and splashing if containers are over filled and shaken at high speed. Always gradually increase the speed to the desired level. Never set the speed beyond the maximum limit.
[][]Remove the plug from the main socket during cleaning.
[][]The shaker should not be operated at the maximum RPM without a load.
[][]Do not leave the shaker unattended when starting the unit. Be sure all flasks are firmly seated in the platform and securely clutch between screwing bars.
[][]Ensure the speed controller knob are turned off before switch on the instrument.

Operation:

[][]Check the calibration sticker to ensure that the instrument is within due date of calibration.
[][]Place the apparatus on a firm level surface ensuring the platform is free from vibration.
[][]Fit the flasks or bottles or beakers to be shaken between two rubber cushioned horizontal screwing bars and adjust to hold them tightly.
[][]Switch ‘ON’ by pressing the ‘control’ knob.
[][]Red dot in the display shows RPM is selected; this can be adjusted by turn the ‘control’ knob to the right up to desired shaking speed (in rpm). Once the correct speed is displayed press the ‘start/stop’ button to begin motion.
[][]In order to use the timer and RPM press the ‘mode’ button. The red dot on the display moves over to time. The display will show the last stored time in minutes.
[][]Select the desired count down time using the control knob. When the display shows the correct time in minutes.
[][]Rotation can be paused at any time by pressing the ‘start/stop’ button.
[][]Rotation will start again by pressing ‘start/stop’ button and the timer will continue to count down.
[][]The timer can be adjusted without halting the unit. When the timer reaches zero, the unit will be automatically halted and alert will sound.
[][]Press ‘start/stop’ button to revert back to the last time and speed values set or select new value.
[][]The shaking will stop automatically after the desired period and sounds an alert.
[][]Switch OFF completely by pressing the ‘control’ knob. The display will show OFF

Calibration:

[][]Calibrate the orbital shaker once in a year.
[][]Switch ‘ON’ the mains.
[][]Switch ‘ON’ the instrument by pressing ‘control’ knob.
[][]Set the desired time (most commonly used time range) using time setting button.
[][]Check the time using a calibrated stop watch and record the time in the calibration information sheet for Orbital shaker as per Annexure-I.

Cleaning procedure:

[][]Clean the instrument once in a week or when required.
[][]Switch ‘OFF’ the instrument and switch ‘OFF’ the mains.
[][]Clean the instrument properly with a non-abrasive cloth moistened in detergent water.
[][]Never use harsh or abrasive cleaning agents.
[][]Allow to dry before use it again.

Annexure:

Annexure-I: Calibration Information Sheet for Orbital Shaker.

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Calibration of Ultrasonic Bath with Operation & Cleaning

Calibration of Ultrasonic Bath, Purpose :

Calibration of Ultrasonic Bath, The purpose of this SOP is to describe the operation, calibration and cleaning of Ultrasonic Bath (Model: Clifton DU-14), used for degassing liquids, dissolving solids in solutions and cleaning laboratory apparatus.

Calibration of Ultrasonic Bath, Scope :

This procedure is applicable for Ultrasonic Bath (Model: Clifton DU-14), installed in the quality control laboratory of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
QC: Quality Control.
[][]Sonication: The act of applying sound energy (usually of the ultrasound type) to agitate particles in a sample.

Executive, QC

[][]To ensure that the instructions of this procedure are correctly followed.
[][]To maintain the records properly as per SOP.
[][]To ensure cleaning of ultrasonic bath maintaining safety rules.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.
[][]Schedule calibration of the instrument at the defined intervals.

Head of Quality Assurance

[][]To ensure the overall implementation of the SOP.
[][]Approval of the SOP.

Procedure:

Precaution(s):

[][]Never put hands in the bath during operations.
[][]Always maintain the liquid level above the minimum level mark.
[][]Disconnect the power supply before moving, emptying or cleaning of bath.
[][]Never operate the unit when dry.
[][]Allow the liquid in the bath to cool down before draining.
[][]Never block or restrict ventilation slots.
[][]Do not place item directly on the bottom of the bath, always make use of the stainless steel basket to suspend the item.
[][]Do not use cleaning fluids which contain concentrations of halogen ions, low pH values or high temperatures when operating the bath for cleaning purposes as these will all increase the risk of corrosion.

Operation:

[][]Check the calibration sticker to ensure that the instrument is within due date of calibration.
[][]Fill the bath with purified water above the ‘MIN’ level mark.
[][]Switch on the bath using the ‘ON/OFF’ switch, located at the rear of the bath.
[][]Place the stainless steel basket into position.
[][]Switch ‘ON’ the heater and press ‘■’ menu button to display “SP1”. Set the desired temperature using ▲ or ▼ key button. Maximum setting 69° C.
[][]After setting temperature, display will flash the temperature four times and then it will be automatically set.
[][]Press ‘■’ menu button twice to display “t”. Set the time using ▲ or ▼ key button.
[][]After setting time, display will flash the time four times and then it will be automatically set or press ‘■’ menu button to set manually.
[][]Place the glassware containing sample onto the stainless steel basket, to prevent touching the bottom of the tank.
[][]To start sonication, press and hold ‘Ο’ button until the Time LED is blinking.
[][]Instrument will stop after set time finished.
[][]Wait until the operation process is completed.
[][]To stop sonication, press and hold ‘Ο’ button until the Time LED is off.
[][]Use suitable tongs to remove the hot glassware from the bath.
[][]Allow the bath to cool.
[][]After completion of work, switch off the bath.
[][]Finally switch off the instrument.

Calibration:

[][]Calibrate the water bath once in a year.
[][]Fill purified water in the bath above the ‘MIN’ level mark.
[][]Switch ‘ON’ the mains.
[][]Switch ‘ON’ the mains of instrument.
[][]Set the desired temperature. Follow operation procedure 7.1.5 to 7.1.6.
[][]Allow 30 minutes to equilibrate.
[][]Check the temperature using a calibrated thermometer/digital thermometer and record the temperature in the calibration information sheet for Ultrasonic bath (as per Annexure-I).
[][]Set the desired time. Follow operation procedure 7.1.7 to 7.1.8
[][]Check the time using a calibrated stop watch and record the time in the calibration information sheet for Ultrasonic bath as per Annexure-I.

Cleaning procedure:

[][]Clean the instrument once in a week or in between when water becomes dirty.
[][]Switch ‘OFF’ the instrument and switch ‘OFF’ the mains.
[][]Remove the basket from the ultrasonic bath.
[][]Wash the basket properly with purified water.
[][]Drain the water from the ultrasonic bath.
[][]Wipe the inner surface of the bath with a non-abrasive cloth moistened in water.
[][]Use 10% nitric acid on a cloth (wear suitable gloves) to remove any scale or deposits.
[][]Fill purified water in the bath above the ‘MIN’ level mark.
[][]Put the basket in to the bath.

Annexure:

Annexure-I: Calibration Information Sheet for Ultrasonic bath.

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Tap Density Apparatus Calibration with operation & cleaning

Tap Density Apparatus Calibration, Purpose :

Tap Density Apparatus Calibration, The purpose of this SOP is to describe the operation, calibration and cleaning of Bulk density apparatus (Model: Electrolab ETD-1020) used for the Bulk density test of raw materials in the quality control laboratory at XX Pharmaceuticals Limited.

Tap Density Apparatus Calibration, Scope :

This procedure is applicable for Bulk density apparatus (Model: Electrolab ETD-1020), installed in the quality control laboratory of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]QC: Quality Control.
[][]USP: United State Pharmacopoeia

Responsibility

Executive, QC

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.
[][]Schedule calibration of the instrument at the defined intervals.

Head of Quality Assurance

[][]Approval of the SOP.
[][]To ensure the overall implementation of the SOP.

Procedure:

Precaution(s):

[][]The equipment should not be set near to room heating equipment or direct sunlight.
[][]Use mask, gloves and safety goggles during handling the instrument.
[][]Disconnect the power supply before cleaning of the instrument.
[][]Prior to use, user must ensure that equipment is calibrated.
[][]Avoid any dust gathering on the bearings.
[][]Do not lubricate the bearings.
[][]Keep the shaft of the cylinder holder and the tip of the cylinder holder clean.
[][]Do not press the cylinder holder when the tapping base of cylinder holder is not touching the anvil.
[][]Place the cylinder in the holder only when the holder is placed on the anvil.

Operation:

[][]Ensure that working area is clean.
[][]Connect power cord of the instrument to mains and switch ‘ON’ the instrument.
[][]Instrument will initialize itself and the display will flash and show the start up screen.

[ELECTROLAB TAP DENSITY
ETD-1020 VER 3.0

[][]Set the mode of operation as USP or USER using the ‘DIGIT SCROLL’ key on the front panel.
[][]In USP mode, instrument will stop after every program and validation; report is available at the end of test.
[][]In USER mode, instrument will stop after the set tap value and no validation and result screen will be available. This method is used only when no. of taps are specified in the method.
[][]Press the ‘METHOD’ key to toggle between USP-I and USP-II method and select the required method.
[][]Press ‘SET’ key to set the test parameter.
[][]Display reads

[TAP COUNT 1: # # # # ▲▼◄
SET : EXIT / Enter : SCROLL

[][]Set the TAP COUNT 1.
[][]Enter the Tap count 1 within 1 to 9999 using the ‘UP/DOWN’ & ‘DIGIT SCROLL’ key.
[][]Press ‘ENTER’ key to go next parameter.
[][]Similarly set TAP COUNT 2 and TAP COUNT 3.
[][]In USP method, set TAP COUNT 1 as 250 taps, TAP COUNT 2 as 500 taps and TAP COUNT 3 as 500 taps.
[][]Set the date and time using the ‘UP/DOWN’ & ‘DIGIT SCROLL’ key.
[][]Select the print option & press ‘SET’ key to scroll back to main menu.
[][]Pass a quantity of material sufficient to perform the test through 20-mesh screen to break up any agglomerates.
[][]Transfer about 100 g sample into a dry 250 ml graduated cylinder with 2 ml accuracy.\
[][]Alternatively transfer a small quantity (less than 100 g) of sample into a 100 ml cylinder with 1ml accuracy to minimize the sample quantity.
[][]Press the ‘START’ key.
[][]Weigh the test sample and enter the weight of test sample.
[][]Press the ‘ENTER’ key to register the weight.
[][]Level the sample without tapping or compacting.
[][]Read the unsettled apparent volume to the nearest graduated unit and enter the volume using the ‘UP/DOWN’ & ‘DIGIT SCROLL’ key.
[][]Press the ‘ENTER’ key to register the volume.
[][]Fix the measuring cylinder into the holder provided for holding the measuring cylinder on the instrument.
[][]Lock the holder assembly.
[][]Press the ‘START’ key again to run the test.
[][]Display will show the elapsed taps and drops per minute.

ELAPSED TAP: # # #
Drops / Min. : # # #

[][]After programmed TAP COUNT 1 is over, measure the tapped volume to its nearest graduated unit.
[][]Enter the measured tapped volume using ‘UP / DOWN’ & ‘DIGIT SCROLL’ Keys.
[][]Press ‘ENTER’ key to register the value.
[][]Press ‘START’ key to continue TAP COUNT 2 program.
[][]Measure the tapped volume at the end of TAP COUNT 2 program and enter the value using ‘UP / DOWN’ & ‘DIGIT SCROLL’ Keys.
[][]The difference between the two counts will be displayed as a result.
[][]If the result after the completion of TAP COUNT 2 is less than 2.0%, press ‘STOP’ key to end the operation and to get the results.
[][]If the result is more than 2.0%, then press ‘START’ key again to start the TAP COUNT 3 program to get a new value.
[][]Repeat the operation till the difference between two succeeding measurements is less than 2.0%.
[][]Press ‘STOP’ key once the desired difference is obtained instrument will display the results.
[][]The results of Bulk density or initial density, tapped density and Hausner ratio and compressibility index will be displayed one after another by using ‘DOWN’ key.
[][]The results shall be recorded separately or taken as a print out.
[][]After operation enter usage details in Operation Logbook of Bulk Density Apparatus as per Annexure – II.

Calibration:

[][]Calibration of Drop distance
[][]Calibrate the instrument once in a year or whenever there is a major maintenance.
[][]Disconnect the instrument from mains.
[][]Gently disassemble the sample holder assembly.
[][]Remove the top cover by unscrewing the holding screws given on the bottom of the instrument i.e. the screws given on the four sides and one screw given on the backside near the power switch. The places are marked for convenience.
[][]Place the sample holder in the slot of USP I and manually rotate the cam wheel so that the holder is at the highest position.
[][]The stem of the holder is now on the top of the highest position of the cam (which is marked as a groove on the wheel.
[][]Measure the distance from base to the bottom of the holder (h1) using a suitable vernier caliper.
[][]Rotate the wheel to get the lowest position, the position from which it started to raise again.
[][]Measure the distance from base to the bottom of the holder (h2) using a suitable vernier caliper.
[][]The difference between the h1 and h2 gives the drop distance.
[][]Record the observations in the calibration information sheet (Annexure –I).
[][]Repeat the same procedure on the USP-II slot.
[][]Record the observations in the calibration information sheet (Annexure –I).
[][]When the distance is not within the prescribed limit, change the teflon bottom of the stem to get the required height.
[][]Carefully replace the top cover and close.
[][]Calibration of Drop rate
[][]Connect the instruments for main and proceed for the calibrations for drops rate.
[][]Switch ‘ON’ the mains.
[][]Select USP-I or USP-II method using ‘METHOD’ key
[][]The indicator light glows in USP-I or USP-II on the front panel
[][]Using ‘SCROLL BAR’ keys, select the USER method and press ‘SET’ key.
[][]Enter the number of taps to 100
[][]Press ‘START’ key and simultaneously start the stopwatch.
[][]Record the time at which the tapping stops in the calibration information sheet (Annexure –I).
[][]Similarly perform the test using 250, 750 and 1250 taps and note the timings
[][]Calculate the drops per minute in both USP-I and USP-II method.
[][]Record the drops per minute in the calibration information sheet (Annexure –I)
[][]If the instrument is out of calibration, inform the Manager, Quality Control.

Cleaning Procedure:

[][]Clean the instrument after every use.
[][]Switch ‘OFF’ the instrument and switch ‘OFF’ the mains.
[][]Remove the cylinders from the apparatus and clean the cylinder.
[][]Clean the apparatus with cotton cloth.
[][]Clean the surrounding areas of instrument with a cloth dampen in water.

Annexure:

Annexure-I: Calibration Information Sheet for Tap Density Apparatus.
Annexure-II: Operation Logbook of Tap Density Apparatus

 

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Electromagnetic Sieve Shaker Calibration with Cleaning & Operation

Electromagnetic Sieve Shaker Calibration, Purpose:

Electromagnetic Sieve Shaker Calibration, The purpose of this SOP is to describe the operation, calibration and cleaning of Electromagnetic sieve shaker (Model: Electrolab EMS-8) used for the sieve analysis in the quality control laboratory at XX Pharmaceuticals Ltd.

Electromagnetic Sieve Shaker Calibration Scope:

This procedure is applicable to the Electromagnetic sieve shaker (Model: Electrolab EMS-8), used for conducting sieve analysis and particle size distribution using test sieves, in the quality control laboratory of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]QC: Quality Control.
[][]ASTM: American Society for Testing and Material.

Responsibilities:

The roles and responsibility is as follows:

Executive, QC

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.
[][]Schedule calibration of the instrument at the defined intervals.

Head of Quality Assurance

[][]Approval of the SOP.
[][]To ensure the overall implementation of the SOP

Procedure:

Precaution(s):

[][]The equipment should not be set near to room heating equipment or direct sunlight.
[][]Use mask, gloves and safety goggles during handling the instrument.

Operation:

[][]Check the machine is clean and calibrated.
[][]Ensure that the working bench is clean.
[][]Switch on the power from its main and power on the instrument.
[][]Display indicates: ELECTRO – MAGNETIC
[][]SIEVE SHAKER EMS-8
[][]Ensure all the sieve diameter and pore size should be as per ASTM standard. Keep received certificate in appropriate place.
[][]Use certified sieve.
[][]Select the sieves required as per monograph/ procedure.
[][]Check the integrity of the sieves.
[][]Ensure the sieve numbers are matching with the ASTM number given on the sieves.
[][]Place the sieves in the descending order of sieve No. on the collecting pan.
[][]Set the sieves on the instrument, shaker ensures that the value of the amplitude is set at the lowest.
[][]Set the desired time (Maximum 99 minutes) by pressing the time key provided below the “TIME” display.
[][]Set the desired amplitude (power level 5 to 20) by pressing the power key provided below the “POWER” display.
[][]Select Continuous or intermittent mode by pressing “CONTNUOUS” or “INTERMITTENT” key respectively.
[][]Weigh the sample and evenly spread the same on the top sieve and close the sieve.
[][]Place the sieve sets on the base of the holder firmly and lift the assembly to touch the top of the holder.
[][]Tight the assembly and then press “START” key to start the operation.
[][]The shifter works during the time and with the power level programmed. In case of intermittent mode, the shifter will start vibrate at interval of 0.5 second.
[][]After completion of this process carefully remove the sieve set.
[][]Collect the samples retained on each sieve and on the collection pan and weigh the quantity of sample retained on each sieve.
[][]Calculate the percentage of the sample retained on each sieve and put the analysis data in the report sheet of electromagnetic sieve shaker.
[][]Check the integrity of the sieves again, if not ok label it as rejected and discard the same as scrap.

Cleaning of the Sieve:

[][]Do not use dissolvent or any hard material for cleaning.
[][]For sieves less than 500 micron use ultrasonic and detergent. The sieves should be gently cleaned by keeping it in ultrasonic for 4 to 5 minutes.
[][]Cleaning with soft brush followed by ultrasonic cleaning can be used for sieves having mesh size more than 500 micron.
[][]After cleaning sieves should be rinsed thoroughly and left to dry in an upright position.

Cleaning of the Sieve Shaker:

[][]Switch ‘OFF’ the instrument and switch ‘OFF’ from the mains.
[][]Clean the outer surface of the instrument with Isopropyl alcohol and dry it with tissue paper.
[][]Clean the surrounding areas of instrument with a cloth dampen in water

Calibration:

[][]Calibration frequency: once in a year and after every maintenance.
[][]Check the time with calibrated and certified clock at 10, 20, 50, 70 and 90 minutes. The tolerance should be ± 1 minute.
[][]After completing the calibration, maintain the calibration record of Sieve shaker as per Annexure-I.

Annexure:

Annexure–I: Calibration Information Sheet for Electromagnetic Sieve Shaker.
Annexure–II: Operation logbook for Electromagnetic Sieve Shaker.
Annexure–III: List of Sieves.

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Karl Fischer Titrator Calibration with operation & cleaning

Karl Fischer Titrator Calibration, Purpose:

Karl Fischer Titrator Calibration, The purpose of this SOP is to describe the operation, standardization of titrants, calibration, cleaning and maintenance of Karl Fischer Titrator (Model: Mettler Toledo V20 Compact) used for the determination of the water content in the quality control laboratory at XX Pharmaceuticals Ltd.

Karl Fischer Titrator Calibration, Scope:

This procedure is applicable to the Karl Fischer Titrator, used for the determination of water content, in the analysis of raw materials, intermediate and formulated drug product, installed in the quality control laboratory of XX Pharmaceuticals Limited.

Definitions/Abbreviation:

[][]SOP: Standard Operating Procedure
[][]QC: Quality Control
[][]KF: Karl Fischer

Responsibilities:

The roles and responsibility is as follows:

Officer/Executive/Sr. Executive,

[][]Quality Control
[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.
[][]Schedule calibration of the instrument at the defined intervals.

Head of Quality Assurance

[][]Approval of the SOP.
[][]To ensure the overall implementation of the SOP.

Procedure:

Precaution(s):

[][]The equipment should not be set near to room heating equipment or direct sunlight.
[][]Use mask, gloves and safety goggles during handling the Karl Fischer reagent and methanol under Fume Cupboard.
[][]Do not change stirring speed between the pre-titration and the titration.
[][]Always take some more volume of liquid sample by a syringe and then inject the desired volume.
[][]Clean and dry syringes and needles before use. Rinse the syringe with the sample solution itself 2 – 3 times and then take the test sample. This will remove the moisture from syringe if any.
[][]While testing various samples of which the moisture contents are roughly known, test the sample having lowest moisture first and then go on to the next in order to avoid contamination.
[][]If moisture content of samples are unknown and very small sample to obtain pilot reading and then adjust the size of sample accordingly. Keep next sample ready and if some time is lapsed between two titrations. Press START, get to the end point then add sample immediately. This will eliminate the error due to lapse of time.
[][]If fresh KF reagent is added to the old stock in KF reservoir, mix the solution in reservoir properly and recalibrate the reagent for new factor.
[][]Keep the titration cell tightly closed with stopper and only open for an instant to add sample fast.
[][]When renewing the reagents, clean the titration cell thoroughly with methanol (or another suitable solvent) and may be dried in an even at approximately 70⁰C.
[][]Adjust the filling rate of dispensing burette to avoid the introduction of air bubbles in the burette.

Operation:

[][]Check the cleanliness of the instrument.
[][]Check the calibration status of the Karl Fischer Titrator.
[][]Check the clarity and color of the titrant.
[][]Switch ON the instrument. The instrument always performs a self-test before the display of the Titrator name appears.

Functional description:

[][]The control panel consists of an integrated touch screen and four additional keys, which are located next to the touch-sensitive surface of the display.
[][]Reset, the current task is aborted Info, calls to the online help for the current contents of the current dialog.
[][]Home, always returns to the Home screen (the blue Home keys are located at the bottom right and left of the touch screen).

Rinse and fill burette:

[][]To fill the burette and tubes with titrant and remove any air bubbles from the system, the burette should be rinsed three times with titrant. To do that, use the manual operation “Rinse burette”. Press Home if the home screen is not already displayed.
[][]Select the Manual button to open the Manual operations dialog and press Burette button.
[][]In the Burette dialog, use the Rinse button to access the parameters for the rinse process.
[][]Select the relevant titrant.
[][]For the “Cycles” parameter, enter “3” for three rinse cycles.
[][]Press Start to start the rinse procedure.
[][]When all rinse procedures will be completed, use the ok button to return to the Rinse dialog. The burette should be filled and the hoses should be free of air bubbles.

Filling the titration beaker:

[][]To fill the titration beaker with solvent, the solvent manager must be attached to the solvent bottle.
[][]In the Pump dialog (Home>Manual>Pump), select the “Fill” value for the “Action” parameter.
[][]The “Reset counter” parameter will be activated.
[][]Press Start.
[][]Titration beaker will be filled with solvent.

Performing a volumetric KF titration:

[][]Fill dried Methanol in glass vessel.
[][]In the Home screen, use the Methods button and select the method type “KF vol”. In the subsequent dialog, select the “Mix Time” and enter required time.
Select start button.
[][]Start analysis dialog will be displayed. In this dialog select Number of sample and put “3” and then press Ok.
[][]Select Start button. The system will perform a pre-titration as a basis for a water-free solvent.
[][]As soon as the continually determined drift value falls below a regulated required value, the system automatically switches to Standby mode. In the Standby mode the Start Concentration button will be activated.
[][]Press the Start Concentration button, weigh about 10 mg of purified water as a standard and add into the titration vessel and then enter the sample weight.
[][]Press Sample ID and put the sample ID.
[][]Confirm with Ok. The analysis will be started automatically.
[][]Perform 3 samples analysis and press Result>Statistic>Print.
[][]Average water content and relative standard deviation (RSD) of 3 samples will obtain on the print out.
[][]Standard value of RSD is not more than 2%.
[][]Press Reset and select start button.
[][]Start analysis dialog will be displayed.
[][]When Start button will be selected in the Start analysis dialog, the system first always performs a pre-titration as a basis for a water-free solvent.
[][]As soon as the continually determined drift value falls below a regulated required value, the system automatically switches to Standby mode. In the Standby mode the Start sample button will be activated.
[][]Press the Start sample button, add the sample and then enter the sample weight.
[][]Press Sample ID and put the sample ID.
[][]Confirm with Ok. The analysis will be started automatically.
[][]After completing titration, the Result dialog will be displayed and printed automatically.

Calibration:

[][]Fill dried Methanol in glass vessel.
[][]Select start button.
[][]Start analysis dialog will be displayed. In this dialog select Number of sample and put “3” and then press Ok.
[][]Select Start button. The system will perform a pre-titration as a basis for a water-free solvent.
[][]As soon as the continually determined drift value falls below a regulated required value, the system automatically switches to Standby mode. In the Standby mode the Start Concentration button will be activated.
[][]Press the Start Concentration button, weigh about 100 mg of Di-sodium tartrate dihydrate as a standard and add into the titration vessel and then enter the sample weight.
[][]Press Sample ID and put the sample ID.
[][]Confirm with Ok. The analysis will be started automatically.
[][]Perform 3 samples analysis and press Result>Statistic>Print.
[][]Average water content and relative standard deviation (RSD) of 3 samples will obtain on the print out.
[][]Standard value of RSD is not more than 1%.
[][]Record the result in the “Calibration Information Sheet for Karl Fischer Titrator” as per Annexure-I.
[][]Affix the label “CALIBRATED” on the instrument if all test results are satisfactory. If the calibration result is out of limit or any discrepancy is during calibration, affix “UNDER Maintenance” label and inform the respective supplier.
[][]Calibrate the instrument once in every six month.

Cleaning:

[][]After completion of the testing, press Drain>Start button for removing the solution from the test compartment and wash with methanol which is used for water determination. Wipe the knob of sample compartment with tissue paper.
[][]Switch ‘OFF’ the instrument and switch ‘OFF’ the mains.
[][]If the drift of the KF solution remains too high, fill the drying tubes with fresh molecular sieve or regenerate molecular sieve in a drying oven at 105 – 150⁰C for at least 24 hrs. Before regeneration rinse the molecular sieve used on the waste bottle with purified water as it contain SO2.
[][]Collect the waste solution into waste beaker at the same time all waste to be thrown to avoid corrosion.
[][]Clean the outer surface of the instrument with Isopropyl alcohol and dry it with tissue paper.

Annexure

Annexure-I: Calibration Information Sheet for Karl Fischer Titrator.
Annexure-II: Operation logbook for Karl Fischer Titrator.

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Calibration of Melting Point Apparatus with operation & cleaning

Calibration of Melting Point Apparatus , Purpose :

Calibration of  Melting Point Apparatus, The purpose of this SOP is to describe the operation, calibration and cleaning of Automatic Melting-point apparatus (Model: BUCHI M-565) used for the determination of the melting point of raw materials in the quality control laboratory at XX Pharmaceuticals Ltd.

Calibration of Melting Point Apparatus, Scope :

This procedure is applicable to the Automatic Melting-Point Apparatus (Model: BUCHI, M-565), installed in the quality control laboratory of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]QC: Quality Control.
[][]Melting point or Melting range: Melting point or Melting range is defined as the point at which or those points of temperature within which, the solid coalesces and is completely melted. The optical properties of most substances change at this transition.

Responsibilities:

The roles and responsibility is as follows:

Sr. Executive/Executive, QC

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.
[][]To ensure cleaning of Melting point apparatus maintaining safety rules.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]Arrange training on the SOP to all concerned personnel.
[][]To ensure implementation of the SOP after training.
[][]Schedule calibration of the instrument at the defined intervals.

Head of Quality Assurance

[][]Approval of the SOP
[][]To ensure the overall implementation of the SOP.

Procedure:

Precautions:

[][]Laboratory coat and safety glasses (to protect eye from capillary tube) must be worn while handling the instrument.
[][]Always ensure that the cooling air outlet at the back of the instrument is not covered so that the air can flow.
[][]Use only the BUCHI sample tubes provided, as other tubes may not correctly fit in the sample holder. Always handle these glass tubes with care.
[][]Never touch the furnace or sample just removed from the furnace. The temperature of the furnace can reach 400°C.
[][]Care should be taken while inserting the capillary into its cavity or taking out from the cavity to avoid breaking, take it out vertically.
[][]Check always colour of the silicone oil. Normally it is colourless. If it observed as yellow or brown, discard the oil. And take fresh oil in that container.
[][]Disconnect the power supply before moving or cleaning of the instrument.
[][]When not in use, keep the Instrument in a safe place.
[][]Prior to use, user must ensure that equipment is calibrated.

Operation:

[][]Check the machine is clean and calibrated.
[][]Prepare the sample to make it powder, if required with an agate mortar.
[][]Fill the sample in capillary tube to a height of approximately 3 – 6 mm with the help of sample loader.
[][]Plug the instruments into an acceptable power source.
[][]Turn the instrument ON by using ‘I/O’ switch in front of the machine.
[][]Choose the Melting Point settings for melting point determination by rotary knob.
[][]Make sure that all samples are removed.
[][]To create a new melting parameter, press ‘Edit’.
[][]Select Start temperature with the rotary knob and press ‘Next’.
[][]Select Stop temperature with the rotary knob and press ‘Next’.
[][]Select Temperature gradient with the rotary and press ‘Save’.
[][]Press ‘START’ to start the determination.
[][]Turn the rotary knob to select a sample ID/Lot. Press ‘Enter’ after selecting each word/number by rotary knob.
[][]When machine reaches the set the temperature, a beep sound will be given and display will show ‘Insert sample & START’.
[][]Insert three capillary tubes containing sample and press ‘START’.
[][]To register additional temperature stamps manually, see the tube through the front window, press the ‘Set’ button for related sample. Each button can be pressed three times. Registered temperature stamps are displayed in green.
[][]After finish, machine will show the result.
[][]To run through the result, rotate the rotary knob.
[][]To replay the recorded melting process, press ‘Relay’.
[][]Press ‘End’ or ‘STOP’ to return to the idle screen.
[][]The result will be printed out automatically or by print option.
[][]Fill up the Log book for Automatic Melting point Apparatus ( as per Annexure-II)
[][]For creating a method:
[][]Press ‘Method’ to enter the method menu.
[][]Press Options-New-ok.
[][]Enter a method name and press ‘SAVE’.
[][]Adjust Start temperature, Stop temperature and Gradient temperature by using rotary knob. Use ‘Next’ button to move from one option to another. After setting the all parameter press ‘SAVE’.

Calibration:

[][]Calibrate the Automatic Melting Point Apparatus once in a year.
[][]Determine the melting point of 4-Nitotolune, Diphenyl acetic acid, Caffeine, potassium nitrate standard.
[][]To start calibration, turn the rotary knob to calibration. Press ‘START’. The instrument automatically heats to the start temperature of the first substance (4-Nitrotolune). Prepare at least six sample of each substance standard.
[][]Press ‘START’ to start the determination. Turn the rotary knob to select a lot/Sample ID and press ‘Enter’. Press ‘Save’ after giving Lot/Sample ID.
[][]Choose the correct Pharmacopoeia melting point value with the rotary knob. The Pharmacopoeia melting point is written on the certified of analysis. Press ‘SAVE’.
[][]Press ‘START’ to continue. Insert three samples and press ‘START’ to start the determination.
[][]After determination, press ‘START’ again to continue and wait for the beep sound and then insert three more samples and press ‘START’.
[][]After each run, the current result is indicated. After six results are obtained with in a standard deviation of ± 0.2°C. The process moves on to the next substance. The process identical for Diphenylacetic Acid, Caffeine and potassium Nitrate and save.
[][]After determination of the melting point of all four standards, compile the results and record the results in Calibration Information Sheet for Automatic Melting Point Apparatus (as per Annexure-I).

Cleaning:

Clean the instrument once in a week or in between when water becomes dirty.
Switch ‘OFF’ the instrument.
De-dust the instrument daily externally with a clean dry cotton cloth.
Remove the glass window from the heating block periodically and wipe it clean with alcohol or acetone. Replace the window with a new one if it will not come completely clean.
Once in a week remove adhered dust by wet mopping using detergent solution. Afterwards wipe the surface with a clean dry cloth to remove traces of detergent and moisture.

Annexure:

Annexure-I: Calibration Information Sheet for Automatic Melting Point Apparatus.
Annexure-I: Operation Log book for Automatic Melting Point Apparatus.

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Calibration of Refractometer with Operation and Cleaning

Calibration of Refractometer, Purpose :

Calibration of Refractometer, The purpose of this SOP is to describe the operation, calibration and cleaning of Refractometer (Model: Rudolph J257) used for the determination of the refractive index of raw materials in the quality control laboratory at XX Pharmaceuticals Ltd.

Calibration of Refractometer, Scope :

This procedure is applicable to the Refractometer (Model: Rudolph J257), installed in the quality control laboratory of XX Pharmaceuticals Limited.

Definitions/Abbreviation:

[][]Standard Operating Procedure (SOP): A written authorized procedure, which gives instructions for performing operations.
[][]QC: Quality Control.
[][]Refractive index: The refractive index of a medium with reference to air is equal to the ratio of the sine of the angle of incidence of a beam of light in the air to the sign of the angle of refraction of the refracted beam in the given medium.

Responsibilities:

The roles and responsibility is as follows:

Officer/Executive/Sr. Executive, Quality Control

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]Arrange training on the SOP to all concerned personnel.
[][]To ensure implementation of the SOP after training.
[][]Schedule calibration of the instrument at the defined intervals.

Head of Quality Assurance

[][]Approval of the SOP.
[][]To ensure overall implementation of the SOP.

Procedure:

Precaution(s):

[][]Clean off samples with water and then with methanol or a suitable solvent as soon as the measurement is completed in a way to avoid possible scratching in the prism.
[][]Do not use the strong solvents such as N,N- Dimethylformamide or N,N-Dimethylacetamide, Cresol, Phenols and other tar acids.
[][]Never use any hard or metallic objects on the prism surface (where the sample to be measured is placed) as scratches quickly spoil the definition of the borderline.
[][]Disconnect the power supply before moving or cleaning of the instrument.
[][]When not in use, keep the instrument in a safe place.
[][]Prior to use, user must ensure that equipment is calibrated.

Operating procedure

[][]Check the machine is calibrated.
[][]Plug the instruments into an acceptable power source.
[][]Turn the instrument ON.
[][]Wait about 30 minutes to warm up the Refractometer.
[][]Carefully clean the polished surface of the fixed prism with water and then with methanol and dry before applying a sample.
[][]Place a few drops of sample on the polished face of the lower Measuring prism.
[][]Lower the sample cover.
[][]Select the option “measure when stable”.
[][]Press the “Read” button to obtain the sample reading.
[][]Take print out of the result.
[][]Record the operation in the logbook.

Calibration with Purified water, Carbon Tetra chloride and Toluene:

[][]Plug the instruments into an acceptable power source.
[][]Turn the instrument ON.
[][]Wait about 30 minutes to warm up the Refractometer.
[][]Carefully clean the polished surface of the fixed prism with water and then with methanol and dry before applying a sample.
[][]Determine the refractive index of the purified water, Toluene and Carbon Tetrachloride at 20°C.
[][]Place a few drops of sample on the polished face of the lower Measuring prism.
[][]Lower the sample cover.
[][]Select the option “measure when stable”.
[][]Press the “Read” button to obtain the sample reading.
[][]Take print out of the result.
[][]Compile the result & take approval for the calibration information sheet (Annexure-I).
[][]Affix the label “CALIBRATED” on the instrument if all test results are satisfactory.
[][]If the equipment found out of calibration limit affix “UNDER Maintenance” label and inform the respective supplier.
[][]Calibration frequency: Once in a year.

Cleaning procedure:

[][]After completion of the testing switch off the instrument and switch off the mains.
[][]Clean the prism surface with purified water or alcohol or xylene or a solvent which will remove sample residue.
[][]Finally clean with purified water.
[][]Wipe it with tissue paper.

Annexure:

Annexure-I: Calibration Information Sheet for Refractometer with Water, Carbon Tetrachloride and Toluene
Annexure-II: Logbook for Refractometer

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Calibration of Viscometer With Operation And Cleaning

Calibration of Viscometer, Purpose :

Calibration of Viscometer, The purpose of this SOP is to describe the operation, calibration and cleaning of viscometer (Model: Brookfield LVDV-II+Pro) used for the measurement of viscosity in the quality control laboratory at XX Pharmaceuticals Ltd.

Calibration of Viscometer, Scope :

This procedure is applicable to the Brookfield viscometer, installed in the quality control laboratory of XX Pharmaceuticals Limited.

Definitions/Abbreviation:

[][]Standard Operating Procedure (SOP): A written authorized procedure, which gives instructions for performing operations.
[][]Viscosity: Viscosity is measure of fluid’s resistance to flow.
[][]FSR: Full Scale Viscosity Range.
[][]cP: Centipoise

Responsibilities:

The roles and responsibility is as follows:

Officer/Executive/Sr. Executive, Quality Control

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]Arrange training on the SOP to all concerned personnel.
[][]To ensure implementation of the SOP after training.
[][]Schedule calibration of the instrument at the defined intervals.

Head of Quality Assurance

[][]Approval of the SOP.
[][]To ensure overall implementation of this SOP.

Procedure:

Precaution(s):

[][]To measure high viscosity, choose a small spindle or select slow speed.
[][]Remove spindle before cleaning.
[][]Prior to operation check the labeling of the viscometer. The label is adjusted using the two leveling screws on the base. Adjust so that the bubble label on the top of the instrument within the circle.
[][]Viscosity measurements should be accepted within the equivalent % of Torque Range from 10% to 100% for any combination of spindle/speed rotation.
[][]Viscosity measurements should be taken under laminar flow conditions, not under turbulent flow conditions.

Calibration procedure:

[][]Switch on the power from its main and power on the viscometer.
[][]Transfer the viscosity standard fluid (Standard Fluid 10, Standard Fluid 500 & Standard Fluid 5000) into 600 ml beaker.
[][]Immerse the beaker along with the spindle into water bath for 1 hour at set temperature 25.0°C.
[][]After 1 hour, check the temperature of the viscosity standard fluid with an accurate thermometer.
[][]Lower the DV-II+ into measurement position of the guard leg.
[][]Attach the spindle to the viscometer. In case of disk – shaped spindle, avoid trapping air bubbles beneath the disk by first immersing the spindle to an angle and then connecting to it to the viscometer.
[][]Measure the viscosity reading normally at 25.0°C ± 0.1°C, must rotate the spindle at least five times before readings are taken.
[][]The viscosity reading should be equal the cP value on the fluid standard to within the combined accuracies of the viscometer & viscosity standard i.e. ± (1% of full scale viscosity range + 1% viscosity Standard Fluid stated value at 25ºC).
[][]Calculate the Full scale viscosity is determined from following equation:
[][]Full scale viscosity [cP] = TK * SMC * 10000/ RPM
Where,
TK = spring torque constant of viscometer (for LVDV-II +Pro model TK value is 0.09373 )
SMC = spindle multiplier constant for spindle [SMC value for the four spindle LV1 (entry code: 61), LV2 (entry code: 62), LV3 (entry code: 63), LV4 (entry code: 64) and LV5 (entry code: 65) are respectively 6.4, 32, 128, 640 and 1280.] [][]RPM: Rotation per minute Compile the result & take approval for the calibration information sheet (Annexure-I).
[][]Carry out the test once in a year.
[][]Affix the label “CALIBRATED” on the instrument if all test results are satisfactory.
[][]If the equipment found out of calibration limit affix “UNDER Maintenance” label and inform the respective Supplier.

Operating procedure:

[][]Check the machine is clean & calibrated.
[][]Make the switch ON of the viscometer.
[][]Let the machine initialize for 10 minutes before performing Auto zero.
[][]Attach the spindle with the lower shaft of the viscometer.
[][]Set the spindle no. by pressing SELECT SPINDLE button.
[][]Set speed by pressing SET SPEED button.
[][]Select the data parameters by pressing SELECT DISPLAY button.
[][]Insert and center spindle in the test materials until the fluid’s level is at the immersion groove on the spindle‘s shaft.
[][]Press the motor ON/OFF/ESCAPE key and turn the motor ‘OFF’ when changing a spindle or changing samples.

Cleaning procedure:

[][]After completion of the testing switch ‘OFF’ the instrument and switch ‘OFF’ the mains.
[][]Remove the spindle from the instrument.
[][]Clean the spindle with respective solvent in which solution of sample is prepared.
[][]Clean the spindle with methanol.
[][]Wipe it with tissue paper.
[][]Place the clean spindle at its respective place in the box.

Annexure:

Annexure-I: Calibration Information Sheet for Digital Viscometer
Annexure-II: Calculation Sheet for Viscometer Calibration
Annexure-III: Range for LV Spindle cP (m PaºS )

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Calibration of pH meter with operation and cleaning

Calibration of pH meter, Purpose :

Calibration of pH meter, The purpose of this SOP is to describe the operation, calibration and cleaning of pH meter (Model: Mettler Toledo Seven Compact S220) used for the measurement of pH in the quality control and microbiology laboratory.

Calibration of pH meter, Scope :

This procedure describes the application of pH meter, for the determination of pH, in the analysis of raw materials, intermediates and formulated drug product in the quality control and microbiology laboratory of xx Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]QC: Quality Control.
[][]pH: The pH is a number which represents conventionally the hydrogen ion concentration of an aqueous solution. It is the measurement of the acidity or alkalinity of an aqueous solution.
[][]Calibration: The set of operations which establish, under specified conditions, the relationship between values indicated by a measuring instrument or measuring system or values represented by a material measure and the corresponding known values of a reference standard.
[][]KCl: Potassium chloride.

Procedure:

Precaution(s):

[][]Store the electrode in 3M KCl solution; never store it in distilled or demonized water or any solution containing heavy metal ions as it may block the electrode membrane.
[][]Always keep the pH electrode wet and rinse it thoroughly with the sample to be measured before use.
[][]Avoid high humidity environments and static discharges since these are detrimental for a stable pH reading.
[][]Do not measure pH of a solution with high temperature.
[][]Try to avoid special measuring solutions such as Sulphide, high Alkaline, Albuminous solutions those can reduce the life of electrode.
[][]Never stir the electrode vigorously in solution during measurement of pH.
[][]After washing, dry the electrode with tissue paper but do not wipe the end of with tissue paper.
[][]Never stir the electrode vigorously in solution during measurement of pH.
[][]After washing, dry the electrode with tissue paper but do not wipe the end of with tissue paper.
[][]Always use fresh and unused buffer for calibration.
[][]Perform a recalibration:
[][]When reference electrode is changed.
[][]After testing aggressive chemicals (such as strong acid or base).

Calibration:

[][]Switch on the power from its main.
[][]Power on the pH meter and printer.
[][]Remove the electrode from the potassium chloride (KCl) solution, rinse it with purified water and soak the excess water with tissue paper very carefully.
[][]Calibrate the instrument daily before use by the three buffer solutions of pH values 7.00, 4.00 and 10.0.
[][]Immerse the electrode in buffer solution of pH value of 7.00 and stir gently and press [CAL] .
[][]Wait until a stable endpoint has been reached.
[][]Hear the ‘beep’ point.
[][]See the sign (/A) at the right side of the display.
[][]Rinse the electrode with purified water and soak the excess water with issue paper very carefully.
[][]Repeat the steps from 7.1.5 to 7.1.9 for second and third calibration for the standard solution of pH values respectively 4.00 and 10.00.
[][]Select “End”.
[][]Select “Save”.
[][]Select “Data”.
[][]Select “Calibration Data”.
[][]Select “pH”.
[][]Select “Review”.
[][]Select “Expertpro ISM”.
[][]Select “Transfer”.
[][]Select “Exit” for 5 times to reach the main menu.
[][]The slope should be 90% – 105%, i.e. at print data, S(B1/B2) and S(B2/B3) = 90% – 105% and offset value will be ± 30 mV, i.e. at print data, off.(B1/B2) and off.(B2/B3) = ±30 mV.

Electrode condition:

DisplaySlope value (%)Condition
Display Icon90 - 105Electrode is in good condition.
Display Icon85 - 89Electrode needs cleaning.
Display Icon84 - 80Electrode is faulty.

Maintenance of the Reference Electrode:

[][]If the electrode slope value falls rapidly, or if the response becomes sluggish or inaccurate, the following procedure should be performed one by one.
[][]Change the reference electrolyte solution every six months.
[][]Degrease the membrane with cotton wool soaked in soap solution.
[][]Soak the tip of the electrode in 0.1M hydrochloric acid overnight.
[][]If all these fail, the electrode must be replaced with a new electrode.
[][]Any replacement of the electrode must be recorded in the log book
[][]Verify the pH of any check buffer (buffer range: 4-9 pH), if reading is within limit (Certificate value ± 0.05), calibration confirms.
[][]Remove the electrode from buffer solution, rinse it with purified water and soak the excess water with tissue paper.
[][]Rinse the electrode with saturated potassium chloride (KCl).
[][]7.1.26 Record the calibration status in Logbook for daily calibration of pH Meter (Seven Compact S220) as per Annexure – I
[][]Power off the pH meter and printer.
[][]Switch off the power from its main.

Operation

[][]Ensure that working area is clean.
[][]Pour enough sample solution into a measuring beaker so that the level of the sample is above the junction of the electrode.
[][]Ensure that the pH meter is cleaned and calibrated on the day use.
[][]Remove the electrode from the potassium chloride (KCl) solution, rinse it with purified water and soak the excess water with tissue paper very carefully. .
[][]Switch on the power its main.
[][]Power on the pH meter and printer.
[][]Gently stir the sample and dip the pH electrode into the solution.
[][]Press [READ] button and wait until a stable endpoint has been reached.
[][]Hear the “beep” sound.
[][]See the sign (/A) at the right side of the display.
[][]Select “Data”.
[][]Select “Measurement Data”.
[][]Select “Review”.
[][]Select “Partial” by using “↓”.
[][]Select “by measurement mode” by using “↓”.
[][]Select “pH”.
[][]Select “transfer”.
[][]Collect the printed result from the printer.
[][]Select “Exit” for 6 (six) times to reach the main display/menu.
[][]Take the electrode out of the solution and rinse with purified water and soak the excess water by tissue paper.
[][]For additional samples repeat the steps from 7.2.7 to 7.2.20 until the sample has been measured.
[][]After taking the measurement, rinse the electrode with saturated potassium chloride (KCl).
[][]Record the measurement data in the Operation Logbook of pH Meter (Seven Compact S220) as per Annexure – II.
[][]Power off the pH meter and printer.
[][]Switch off the power from its main.

Cleaning and maintenance:

[][]Clean the outside case of the pH meter using a mild detergent or disinfectant (e.g.70% ethanol) if required.
[][]Clean the area around the pH meter and wipe away any spillage immediately. Special care should be exercised when cleaning up concentrated HCl (usually) or concentrated NaOH (usually) used for adjusting the pH of solutions.
[][]When required, clean all wires and contacts to avoid corrosion.
[][]Inspect the cables of the electrodes for any signs of broken insulation.
[][]Inspect the pH electrode for any cracks in its stem or bulb.
[][]Rinse off any salt deposits on the top of the electrode using water.
[][]If contamination of the glass bulb is suspected, restoration can be attempted as follows:
[][]Soak electrode in 0.1 M HCl or 0.1 N HNO3 for 15 minutes.
[][]Oily or greasy deposits may be removed by methanol.
[][]After the cleaning stage, rinse the electrode in distilled water and replace the internal filling solution (4M KCl if appropriate) for at least 1 hour before taking any measurements.
[][]Make sure the electrode is always kept filled with the appropriate filling solution.

Annexure: Calibration of pH meter

Annexure-I: Logbook for daily calibration of Seven Compact S220 pH Meter.
Annexure-II: Operation Logbook of Seven Compact S220 pH Meter.

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Calibration of Conductivity Meter with Operation and Cleaning

Calibration of Conductivity, Purpose:

Calibration of Conductivity, The purpose of this SOP is to describe the operation, calibration and cleaning of Conductivity meter (Model: Mettler Toledo Seven Compact S-230) used for the measurement of conductivity of water and any other liquid/solution in the quality control laboratory.

Calibration of Conductivity Meter Scope:

This procedure describes the application of Conductivity meter used for the measurement of conductivity of water any other liquid/solution in the quality control laboratory of XX Pharmaceuticals Ltd.

Definitions/Abbreviation:

[][]SOP: Standard Operating Procedure
[][]QC: Quality Control
[][]Conductivity: Conductivity is the ability of a material to conduct electric current.

Responsibilities:

Officer/Executive/Sr. Executive, Quality Control

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.

Head of Quality Assurance

[][]Approval of the SOP.
[][]To ensure the overall implementation of the SOP.
[][]Schedule calibration of the instrument at the defined intervals.

Procedure:

Precaution(s):

[][]Never unscrew the two halves of the housing.
[][]Any spillage should be wiped off immediately some solvents might cause corrosion of the housing.
[][]Avoid the following environment influences:
[][]Powerful vibrations
[][]Direct sunlight
[][]Atmospheric humidity greater than 80%
[][]Corrosive gas atmosphere
[][]Temperature below 5˚C and above 40˚C
[][]Powerful electric or magnetic fields.

Calibration:

[][]Calibrate the instrument on the day of use.
[][]Ensure that working area is clean.
[][]Power on from its main.
[][]Switch on the instrument and printer.
[][]Press “Menu”.
[][]Select “Calibration setting”, then “Calibration standard”.
[][]Select “Predefined standard”, then “Predefined international”.
[][]Select “Supplied standard value of 84 µs/cm, then press “Exit” 2 times return menu.
[][]Take standard into a clean beaker.
[][]Place the electrode into the standard solution.
[][]Press [CAL] wait until a stable endpoint has been reached.
[][]Wait Hear the “beep” sound.
[][]See the sign (/A) at the right side of the display.
[][]Select “Save”, then Select “Data”.
[][]Select “Calibration Data”, then select “Review”.
[][]Select “In Lab 741”, and then select “Transfer” to print the result.

Operation: Calibration of Conductivity Meter

[][]Ensure that working area is clean.
[][]Pour sample into a clean beaker.
[][]Switch on the power its main.
[][]Power on the conductivity meter and printer.
[][]Place the electrode into the sample.
[][]Gently stir the sample and dip the conductivity electrode into the solution.
[][]Press wait until a stable endpoint has been reached.
[][]Hear the “beep” sound.
[][]See the sign (/A) at the right side of the display.
[][]Select “Data”, then “Measurement Data”.
[][]Select “Review”, then “Partial” by using “↓”.
[][]Select “transfer”.
[][]Collect the printed result from the printer.
[][]Select “Exit” for 5 (Five) times to reach the main display/menu.
[][]Record the measurement data in the Operation Logbook of Conductivity meter as per Annexure-II.
[][]Power off the conductivity meter and printer.
[][]Switch off the power from its main.

Cleaning and maintenance:

[][]Wipe the conductivity meter with damp cloth. The housing of the instrument may attack by some organic solvents, such as toluene, xylene and methyl ethyl ketone.

[][]Wipe away any spillage immediately.

Annexure:

Annexure-I: Logbook for Daily Calibration of Conductivity Meter.
Annexure-II: Operation Logbook of Conductivity Meter.

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Calibration of Dissolution Tester with Operation and Cleaning

Calibration of Dissolution Tester Purpose :

Calibration of Dissolution Tester; The purpose of this SOP is to describe the operation, calibration and cleaning of Dissolution Tester (Model: Electrolab, TDT-08L).

Scope :

This procedure is applicable for Dissolution Tester (Model: Electrolab, TDT-08L), installed in the quality control laboratory at general block of XX Pharmaceuticals Limited.

Definitions/Abbreviation:

[][]SOP: Standard Operating Procedure
[][]QC: Quality Control
[][]Dissolution test: Dissolution test is a means to monitor the rate of release of a drug substance from a dosage form to ensure consistency of manufacture and compliance with release specifications.
[][]RPM: Rotations per minute
[][]LED: Light emitting diode
[][]Concentricity: The quality of having the same center (as circles inside one another)
[][]Wobble: Move sideways or in an unsteady way
[][]NMT: Not more than

Responsibilities:

The roles and responsibility is as follows:

Officer/Executive/Sr. Executive, Quality Control

[][]To ensure that the instructions of this procedure are correctly followed.
[][]To ensure cleaning of dissolution tester maintaining safety rules.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.
[][]Schedule calibration of the instrument at the defined intervals.

Head of Quality Assurance

[][]Approval of the SOP
[][]To ensure the overall implementation of the SOP.

Procedure:

[][]General precautions or operational safety:
[][]Do not start the heater if there is no water in the tank.
[][]Always maintain the liquid level within the tank above the minimum level mark using purified water only.
[][]Disconnect the power supply before moving, emptying or cleaning of bath.
[][]Spillage must be cleaned up immediately after use.
[][]Do not use any aggressive material or strong solvent to clean the jar and water bath.
[][]Locate the system on a level bench without movement or distortion.
[][]Do not hold the stirrer while in operation.
[][]For lifting up the stirrer, make sure the paddles are stop.
[][]Do not disturb the sensor tube while cleaning the tank.
[][]External probe should be handled with care.
[][]Use sinkers if the dosage form unit floats. Close the vessels with the cover during Operation.

Operation:

[][]Connect the instrument to the main power supply.
[][]Ensure the calibration status is valid.
[][]Lift the head by approximately 20 cm by pressing lift UP arrow push button.
[][]Fill the purified water in the tank up to the mark level without jars. Place the tank on the base of the instrument such that four screws at the bottom of the tank fits in to the holes on the base plate and heater cable is at the rear side of the instrument.
[][]Connect the heater plug in the socket provided at the right hand side of the stirrer unit. Add 0.01% Cetyl puridinium chloride or Sodium benzoate or Bronidiol to prevent fungal growth in the water bath.
[][]Connect the power cord from the ETC-11L to TDT-08L in the socket provided on the rear side of the instrument.
[][]Turn on the red colored power switch provided on the front side of ETC-11L.
[][]The yellow colored switch of the Heater will remain always on.
[][]Switch on the power switch provided on the rear

ELECTROLAB
TDT-08L VER 3.50C
DISSOLUTION
TEST APPARATUS

[][]After the power flash screen an idle screen will be displayed showing the last Mode. Protocol no. selected, RPM, Bath temperature and Temp by external probe.
[][]There are 20 protocols. We can assign 20 types of samples against these protocols.
[][]Set the protocol with // keys.
[][]Insert the test vessels in the water bath.
[][]Insert the paddles/basket in the stirrer unit.
[][]Press TEMP key from the front panel. Temperature setting screen will be displayed.
[][]Using // key set the temperature. Set the temperature to 37.7ºC so that the jar temperature reaches to 37ºC.
[][]Press F1 to on the heater. The [Temp. ON] indicator will flash on.
[][]Press ENTER key to register the temperature and come out of the TEMP mode. An idle screen will be displayed.
[][]Press RPM key. Adjust the RPM with // keys.
[][]Press ENTER to register the RPM and come out of the screen.
[][]To set the time press TIME key. A screen will appear like

SAMP. No = 00 OF 00 
SAMP. INTV. = 00 Hr: 00 Mn

[][]Set the sampling number 01 OF 01. Set total dissolution time (as per test method for a particular product) in SAMP. INTV by using // keys.
[][]Press ENTER key to register the time and come out to the initial screen.
[][]Wait to raise the bath temperature up to the desired level.
[][]When the temperature will raise to desired level the [READY] indicator will flash on.
[][]Add dissolution media into individual test vessel as per test method. Measure media temperature with the sensor. Wait until the temperature reaches to 37 ± 0.5°C.
[][]Place sample in vessels in case of paddle apparatus taking care to exclude air bubbles from the surface of the dosage form unit.
[][]In case of basket apparatus place sample in dry baskets, attach the shaft into stirrer unit and lower down the stirrer unit into medium. By lift DOWN key.
[][]Immediately press START key to run the operation.
[][]The screen will show the Elapse time of operation.
[][]After completion of the time interval the instrument will give beep sound.
[][]Lift the stirrer using the lift UP key.
[][]Withdraw the dissolution medium with suitable pipette from a zone midway between the surface of the dissolution medium and the top of rotating paddle through the head nozzle, not less than 1 cm from the vessel wall.
[][]The sampling has to be filtered immediately after completion of the sampling.
[][]After completion of work, switch ‘OFF’ the instrument.
[][]Switch ‘OFF’ the mains when not required.
[][]Fill up the operation log book for Dissolution tester as per Annexure-III.

Physical Calibration

Frequency: Perform mechanical calibration of the dissolution tester once in every six months or if the system has been moved, serviced or a malfunction is suspected.

For Temperature Calibration:

[][]Switch on the mains
[][]Set the temperature to 37°C by following the temperature setting procedure given in operation.
[][]Ensure that the jars are filled with water
[][]Allow the instrument to stabilize
[][]Measure the temperature of the water bath and of each jar with a calibrated thermometer and compare the result against the digital display on the apparatus.
[][]Record the observation as per Annexure-I.
[][]Acceptance Criteria: 37°C ± 0.5°C.

For RPM Calibration:

[][]Switch on the mains.
[][]Set the RPM to 50 as per procedure given in the operation.
[][]Start the stirrer and measure the RPM by using calibrated tachometer.
[][]Record the observation as per Annexure-I.
[][]Similarly check the RPM 75, 100, and 150 and record the observations.
[][]Acceptable criteria: ± 4% of set value.

For Time Calibration:

[][]Switch on the mains.
[][]Set the desired time (30 and 45 Minutes) by following the temperature setting procedure given in operation.
[][]Check the time using a calibrated stop watch and record the observations as per Annexure-I.
[][]Acceptable criteria: ± 2% of set value.

Chemical Calibration (Dissolution Performance Verification Testing)

Frequency: Perform chemical calibration of the dissolution tester once in a year or if the system has been moved, serviced or a malfunction is suspected.

For USP Dissolution Apparatus 1 (basket) and Apparatus 2 (paddle):

[][]If the instrument is outside calibration, a label of “Out of calibration” is placed.
[][]Apparatus must be calibrated with the following :

Disintegrating Type – USP Prednisone Tablets 10 mg at 50 rpm

[][]Non-disintegrating Type – USP Salicylic Acid Tablets 300 mg at 100 rpm
[][]Checking Standards in the on line-USP and printing Lot-Specific Standard Certificates. Verifies Standard Lots are current within expiry.
[][]Disintegrating Type – USP Prednisone tablets 10 mg at 50 rpm:
[][]Follow the directions for storage and use on the label of the reference standard.
[][]If drying instructions are included on the label, only dry sufficient quantity required for the test (use a clean, dry vessel when drying and not the original container).
[][]Standard solutions must be prepared on the day of use.

Prednisone Standard Preparation (Standards must be prepared in duplicate):

[][]Accurately weigh 20 mg Prednisone standard into a 100 ml volumetric flask containing 5 ml of methanol.
[][]Sonicate to dissolve and dilute to volume with distilled or purified water and mix well.
[][]Further dilute 5.0 ml of this solution to 100 ml with distilled or purified water and mix well.

Dissolution Medium Preparation and De-aeration:

[][]Filter the dissolution medium (Distilled or purified water 500 ml) with the aid of a vacuum through a 0.45 µm-porosity membrane filter into a suitable filtering flask.

Test Procedure:

[][]Using a volumetric flask, measure 500 ml distilled or purified water into each of the six vessels.
[][]Allow medium to equilibrate for approximately 30 minutes before test is commenced.
[][]When dissolution bath has equilibrated, check the temperature of each vessel is 37.0°C ± 0.5°C.
[][]Carefully weigh 6 de-dusted USP Prednisone Tablets 10 mg.
[][]Drop one previously de-dusted tablet into each of the vessels via the sample holes in the lids, raising the stirrer shaft fully before dropping the tablet into the vessel, and pushing the shaft fully down when the tablet has reached the bottom.
[][]Operate the apparatus at 50 rpm for 30 minutes.
[][]After 30 minutes withdraw approximately 50 ml midway between the surface of the dissolution medium and the top of the blade, not less than 1cm from the vessel wall.
[][]Filter through a Whatman Number 1 filter paper, discarding the first few ml of filtrate.
[][]Scan the standard from 300-200 nm to obtain the maximum absorbance at the optimum wavelength (approximately 242 nm).
[][]Determine the absorbance of the six samples at that wavelength in fixed mode.
[][]Calculate the percentage prednisone dissolved for all 8 stations using the following calculations:
Absorbance of Sample x Standard Concentration (mg/l) x Standard Potency x 100] divided by
[Absorbance of Standard x Sample Concentration if 100% dissolved (C100) x 100]

Acceptance Criteria:

[][]Check the percentage released limit of USP dissolution calibration tablets (Disintegration type: Prednisone tablets) from the respective batch certificate provided by USP.
[][]If any one station is outside of specification, place an “Instrument out of calibration, DO NOT USE” label on the instrument.
[][]Inform In-charge, QC; if the results do not meet the criteria.

Test interpretation:

[][]The apparatus shall be suitable if the individual calculated values at each indicated speed are within the range specified in the tablet obtained with the each lot of tablets.
[][]Note: An amount of alcohol not to exceed 5% of the total volume of the standard solution may be used to bring the prednisone standard into solution prior to dilution with dissolution medium.

Recording of Results:

[][]All relevant information on the calibration must be completed on Annexure-II.
[][]When all the results have been checked affix a Calibration label to the instrument.

Cleaning procedure

[][]Lift the stirrer unit by using “lift UP” key.
[][]Switch ‘OFF’ the heater.
[][]Switch ‘OFF’ the instrument.
[][]Switch ‘OFF’ the mains.
[][]Remove the plug from the main socket.
[][]De-dust the outer surface of the instrument with a clean dry cloth every day.
[][]Clean apparatus after completion of every dissolution test.
[][]Remove the test vessels from their place and discard the medium.
[][]Wash each vessel with purified water and then set them inside the dissolution bath number wise.
[][]Remove basket/paddle apparatus from the dissolution tester. Wash them with purified water and dry with tissue paper and keep at dedicated place.
[][]Clean and replace the water from dissolution bath fortnightly (once in every two weeks) or if necessary.
[][]Remove all vessels from the dissolution bath.
[][]Remove the basket/ paddle apparatus from the stirrer unit.
[][]Remove the circulating pipe which is provided at the right rare side of the dissolution bath.
[][]Start the circulation pump from the option menu and drain the dirty water in a waste water bucket.
[][]Insert the circulating pump in its proper place.
[][]Wash the dissolution bath with potable water, detergent solution and then again with potable water sequentially until no foam of detergent remains in the bath.
[][]Wash the bath finally with purified water and fill the bath with the same up to the level mark.

 

Annexure Download Here

Annexure-I: Physical Calibration Information Sheet for Dissolution Teste
Annexure-II: Chemical Calibration Information Sheet for Dissolution Tester
Annexure-III: Operation Log book for Dissolution Tester

 

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Calibration of UV-Vis Spectrophotometer With Operation & Cleaning

Calibration of UV-Vis Spectrophotometer Purpose :

Calibration of UV-Vis Spectrophotometer, The purpose of this SOP is to describe the operation, calibration and cleaning of UV-Vis Spectrophotometer (Shimadzu, UV-1800) used in the quality control laboratory of General block at XX Pharmaceuticals Limited.

Scope :

This procedure is applicable for UV-Vis Spectrophotometer (Shimadzu, UV-1800), installed in the quality control laboratory of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]QC: Quality Control.
[][]UV-Vis: Ultraviolet and Visible.

Responsibilities:

Sr. Executive/Executive, QC

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.
[][]Schedule calibration of the instrument at the defined intervals.

Head of Quality Assurance

[][]To ensure the overall implementation of the SOP.
[][]Approval of the SOP

Procedure:

Precaution(s):

[][]Prior to use, user must ensure that equipment is calibrated.
[][]Handle the measuring cell with care.
[][]Do not forget to turn off the instrument after use or if the next reading will be taken after long period of time.

Operation: Calibration of UV-Vis Spectrophotometer

[][]Switch ‘ON’ the Computer, Printer and Spectrophotometer.
[][]Wait until initialization is completed and the initialization result will be displayed in the outlet screen of the machine, finally green signal will appear in the outlet light-bar.
[][]Double click on ‘UV probe’ icon in the computer to run the software.
[][]Press ‘Connect’ icon to establish communications with the machine and machine will be ready for any type of analysis in Photometric/ Spectrum mode.

Measurement in spectrum mode

[][]Click “Spectrum” icon to perform measurement in spectrum mode.
[][]Click “Method” icon to set the desired parameters according to the requirement as follows:
[][]Click ‘Measurement’ icon then set following steps:
[][]Wavelength Range: Start & End- as required.
[][]Scan Speed : Fast/ Medium/ Slow/ Very slow
[][]Sampling Interval : As required
[][]Scan mode: Single/ Auto
[][]Input desired filename for the respective data to preserve in distinguishable data-path.
[][]Click ‘Instrument parameter’ to set the measuring mode as: Absorbance or transmittance.
[][]Finally press “OK” to resolve the setup, click ‘Close’.
[][]Click ‘ Baseline’ icon followed by ‘OK’ for baseline correction.
[][]Rinse both the cells with respective blank solution & wipe properly the outer surface of the cell with tissue paper. Put the cells in cell holder and close the curvature.

[][]Click “Auto zero” to compensate the blank reading.
[][]Remove one cell (front side) and after proper rinsing with the required sample solutions fill the cell with sample solution, wipe properly the outer surface of the cell with tissue paper & Set sample in the cell holder and finally close the curvature.
[][]Click “START”. The photometer status window will show “Slewing….” and it will be followed by the active reading.
[][]After completion of measurement click ‘Point pick’ for determining the absorbance/ transmittance at definite wavelength or Click ‘Peak pick’ for determining the absorbance/ transmittance at a given wavelength range.
[][]Click ‘Save’ to preserve the data and print the data on respective report format.
[][]Wash the measuring cells properly with purified water and preserve in appropriate place.

Measurement in quantitative mode

[][]Click “Photometric” icon to perform measurement in quantitative mode.
[][]Click “Method” icon to set the desired parameters according to the requirement as follows:
[][]Wavelength type: point
[][]Input required wavelength in ‘Wavelength (nm)’, click ‘Add’ then press Next
[][]Input ‘Type’ as ‘Single point’, Formula as ‘Fixed Wavelength’. In ‘WL1’ activate the required wavelength, then input standard concentration in ‘STD Concentration’, click Next>Next>Next.
[][]Finally in ‘Photometric method’ input ‘filename’ for the respective data to preserve in distinguishable data-path. Also input ‘Title’ if any, user name in ‘Analyst’ and fill-up ‘Comments’ if any.
[][]Press “Finish” to resolve the setup, click ‘Close’.
[][]Rinse both the cells with respective blank solution &swipe properly the outer surface of the cell with tissue paper. Put the cells in cell holder and close the curvature.

[][]Click “Autozero” to compensate the blank reading.

[][]Remove one cell (front side) and after proper rinsing with the required standard solutions fill the cell with standard solution, wipe properly the outer surface of the cell with tissue paper & Set standard solution in the cell holder and finally close the curvature.
[][]In the ‘Standard table’ input the standard description in the column for ‘Sample ID’, Click on ‘WL column’ and finally click ‘Read Std’ icon to measure the result.
[][]Remove the standard solution cell (front side) and after proper rinsing with the required sample solutions fill the cell with sample solution, wipe properly the outer surface of the cell with tissue paper & Set sample in the cell holder and finally close the curvature.
[][]In the ‘Sample table’ input the sample description in the column for ‘Sample ID’, Click on ‘WL column’ and finally click ‘Read Unk.’ icon to measure the result.
[][]Click ‘Save’ to preserve the data and print the data on respective report format.
[][]Wash the measuring cells properly with purified water and preserve in appropriate place.
[][]Click ‘Disconnect’ icon to detach the software from the machine.
[][]Exit from the ‘UV probe’ software by closing the window. Put off the power of equipment, printer and computer.

Calibration of UV-Vis Spectrophotometer:

[][]Calibrate the UV-Vis Spectrophotometer at 6 month’s frequency either by following procedure or as per supplier’s protocol:

Wave length Scanning

[][]Set desired start wavelength i.e. higher end of the desired spectrum and desired wavelength expansion. Scan the desired wavelength.

Control of Wavelengths

[][]Verify the wavelength at 241.15 nm, 287.15 nm, 361.5 nm & 536.3 nm using the absorption maximum of Holmium perchlorate solution (4% w/v solution of holmium oxide in a solution of perchloric acid containing 14.1% w/v of HClO4). The permitted tolerance is ± 1 nm for the ultraviolet range and ± 3 nm for the visible range. Record data in calibration information sheet as per Annexure-I .

Control of Absorbance

[][]Check the absorbance using a solution of potassium dichromate at the wavelengths indicated in (Annexure-I) which gives for each wavelength the exact values and the permitted limits of the specific absorbance. The tolerance for the absorbance is ± 0.01.
[][]For the control of absorbance, use solutions of potassium dichromate which has previously been dried to a constant mass at 130° C. For the control of absorbance at 235 nm, 257 nm, 313 nm and 350 nm, dissolve 57.0-63.0 mg of potassium dichromate in 0.005 M Sulphuric acid and dilute to 1000.0 ml with the same acid. For the control of absorbance at 430 nm, dissolve 57.0-63.0 mg of potassium dichromate in 0.005 M sulphuric acid and dilute to 100.0 ml with the same acid.
[][]Measure at a path length of 1 cm, at the wavelength 235 nm, 257 nm, 313 nm, 350 nm and 430 nm against 0.005 M Sulphuric acid as blank. Record data in calibration information sheet as per Annexure-I.

Limit of Stray light

[][]Detect stray light at a given wavelength with suitable solutions: for example the absorbance of a 12 g/l solution of potassium chloride in a 1 cm cell increases steeply between 220 nm and 200 nm and is greater than 2.0 at 198 nm when compared with water as compensation liquid. Record data in calibration information sheet as per Annexure-II.

Resolution (for qualitative analysis)

[][]Prepare a 0.02% v/v solution of toluene in hexane. Use hexane as a blank. The minimum ratio of the absorbance at the maximum at 269 nm to that at the minimum at 266 nm is not less than 1.5 unless otherwise stated in the monograph. Suitable certified reference materials may also be used. Record data in calibration information sheet as per Annexure-II.

Path length measurement of cell

[][]The tolerance on the path length of the cells used is ± 0.005 cm. When filled with the same solvent, the cells intended to contain the solution to be examined and the compensation liquid must have the same transmittance. If this is not the case, an appropriate correction must be applied.
The cells must be cleaned and handled with care.
[][]Carryout the test once before first use of a new cell.
[][]Affix the label “CALIBRATED “on the equipment if all results are satisfactory. If the equipment found out of calibration limit affix “NOT FIT FOR USE” label and call Supplier.

Cleaning procedure: Calibration of UV-Vis Spectrophotometer

[][]After completion of each analysis, clean the UV-Vis spectrophotometer as follows:
[][]Remove cuvette from the sample compartment.
[][]Remove the solution from the cuvette and wash with respective solvent in which solution is prepared.
[][]Rinse with water and then with methanol and wipe with tissue paper.
[][]Air dry and keep it at dedicated place.
[][]When required, clean the outer surface of the instrument with Isopropyl alcohol and dry it with tissue
paper.

Annexure:

Annexure-I: Calibration Information Sheet for UV-Vis Spectrophotometer (Control of Wavelength and Control of Absorbance)
Annexure-II: Calibration Information Sheet for UV-Vis Spectrophotometer (Resolution, Limit of Stray light)
Annexure-III: Operation Logbook for UV-Vis Spectrophotometer

 

 

 

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Calibration of FTIR Spectrophotometer with Cleaning and Operation

Calibration of FTIR, Purpose:

Calibration of FTIR, The purpose of this SOP is to describe the operation, calibration and cleaning of FTIR Spectrophotometer (Shimadzu, IR Affinity-1) used in the quality control laboratory at XX Pharmaceuticals Limited.

Scope

This procedure is applicable for FTIR Spectrophotometer (Shimadzu, IR Affinity-1), installed in the quality control laboratory of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

Standard Operating Procedure (SOP): Standard Operating Procedure. A written authorized procedure, which gives instructions for performing operations.

[][]QC: Quality Control.

[][]FTIR: Fourier Transform Infrared.

Responsibilities

[][]Executive/ Sr. Executive, QC

[][]To ensure that this procedure is followed.

[][]To maintain the records properly as per SOP

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.
[][]Schedule calibration of the instrument at the defined intervals.

Head of Quality Assurance

[][]Approval of the SOP.
[][]To ensure the overall implementation of the SOP.

Procedure: Calibration of FTIR

General Procedure:

[][]Ensure that the instrument is clean and calibrated.
[][]Connect the instrument properly with the power supply.
[][]Switch “ON” the main switch, power switch of the instrument situated at the backside panel, printer and computer.
[][]Allow the instrument initialize for at least 1 hour.

Disk preparation for solid sample:

[][]Mix 5 to 10 mg of sample with 200 to 400 mg of Potassium Bromide (KBr) [IR Grade].
[][]Grind the mixture to very fine powder with agate mortar.
[][]Pour the mixture into the barrel and carefully insert the plunger with its polished face downward.
[][]Maintain the hydraulic pressure 50 KN to 60 KN of the barrel for 1-2 minutes.
[][]Release the pressure and take out the disk from the barrel.
[][]For sample of liquid material using sealed liquid cell:
[][]Inject the liquid sample (pure or in solution) in sealed liquid cell.
[][]Plug to close both the slots of sealed liquid cell.
[][]For sample of liquid material which converted to solid (Nujol preparation) and measurement using NaCl demountable liquid cell:
[][]Put the cell window on the cell window holder and place the spacer of appropriate thickness on the cell window.
[][]Take 3 to 5 mg of sample with 2 to 3 drop of Nujol in a mortar and mix properly.
[][]Insert sample inside the spacer with a spatula. Put another cell window on the spacer and fit the metal plate on it.
[][]Fasten those plates with the four screws. Do not fix them with excessive force. It is enough to fasten them tightly by hand.

Operation Procedure (FTIR): calibration of FTIR

[][]Double click on “IRsolution” software icon.
[][]Press Measure
[][]Select FTIR Parameters in parameter window as follows:
[][]Data :
[][]Measurement Mode: % Transmitance ,
[][]Resolution: 2
[][]Apodization: Happ-Genzel
[][]No of Scans: 10
[][]Range (cm-1): Min: 400 cm-1 Max: 4000 cm-1
[][]Instrument:
[][]Beam: Internal
[][]Detector: Standard
[][]Mirror speed: 2.8
[][]More:
[][]Mode: Power
[][]Remove sample, if any, from the sample compartment.
[][]Click on Measurement then “Initialize” then “Yes”.

[][]After successful initialization, click BKG then “OK”. Wait till window on the screen is displayed as last Bkg.
[][]After ‘Bkg scan’, put the sample disk in the sample chamber, with the help of sample holder and close the chamber.
[][]Enter the Sample name, Batch No., Sample ID. in comment box and enter the data file location in Data file box.
[][]Click Sample to measure sample. Wait till the actual sample IR scan is displayed.
[][]Click on the spectrum window. Select Calculate  peak table. Type threshold: 60.00.
[][]Click on Calc, OK
[][]Compare the Spectrum in computer screen. View the IR scan of standard, click on Manipulation 2 then “Purity” then “Yes”.
[][]Again view the IR scan of sample, click on Manipulation 2  “Purity”  “Calc”  “OK”.
[][]After comparison with standard and sample then click file and open file as required. Then click Window  “Join visible”  “Calc”  “OK”.
[][]Purity index should be within 0 .9500 – 1.0000.
[][]A disc is rejected if visual examination shows lack of uniform transparency or when transmittance at about 2000 cm-1 (5 µm) in the absence of a specific absorption band is less than 60 % without compensation, unless otherwise prescribed in individual monograph.
[][]For printing of spectrum, click File  “Print preview”. Select respective necessary template and then print.
[][]Close the parameter window and the Software window.
[][]Shutdown PC, switch off Printer.
[][]Power OFF Spectrophotometer.
[][]Take out the liquid cell from the instrument.
[][]Discard the disk /Nujol / liquid sample.
[][]Clean the holder and liquid cell with dry and clean tissue paper.
[][]In case of sealed liquid cell mop and wash with IPA or absolute Ethanol and in case of demountable liquid cell mop and wash with Chloroform or Carbon Tetrachloride.
[][]Keep them in specified desiccator.
[][]Rub mortar, pestle, barrel & plunger with tissue paper to make them free from dust.
[][]Mop them with a tissue paper soaked in absolute ethanol.
[][]Keep them in a desiccator for next operation.
[][]Record all analysis in operation log book as per Annexure-II.

Operation Procedure (ATR):

Running a sample:

[][]Turn on the computer and crick on the respective software on the desktop.
[][]Set the MIRacle/ MIRacle A Base Unit to the instrument.
[][]Before initialization, set FTIR Parameters in parameter window as follows:
[][]Data :
[][]Measurement Mode: % Transmitance ,
[][]Resolution:2
[][]Apodization: Happ-Genzel
[][]No of Scans: 10
[][]Range (cm-1): Min : 700 cm-1 Max : 4000 cm-1
[][]Click on Measurement then “Initialize” then “Yes”. Click “cancel” option for auto adjustment.
[][]Click on Measurement then “Auto adjustment (Fine)” then “Yes”.
[][]After autoadjustment, click BKG then “OK”. Wait till window on the screen is displayed as last Bkg.
[][]Set the clamp to the base. Place sample on the ZnSe crystal- Liquids -place a drop of sample on the ZnSe crystal. Place a small neat solid sample on the ZnSe crystal with a spatula. Adjust the knob of the ATR until the pressure reads 12.
[][]Make sure that no acid sample (pH below 5), strong alkaline sample (pH more than 9) or liquid which give damage to PTFE should not be place on ZnSe prism.
[][]Enter the Sample name, Batch No., Sample ID. in comment box and enter the data file location in Data file box. Click Sample to measure sample. Wait till the actual sample ATR scan is displayed.

Working up the Data:

[][]Compare the Spectrum in computer screen. View the ATR scan of standard, click on Manipulation 2 then “Purity” then “Yes”.
[][]Again view the ATR scan of sample, click on Manipulation 2  “Purity”  “Calc”  “OK”.
[][]After comparison with standard and sample then click file and open file as required. Then click Window  “Join visible”  “Calc”  “OK”.
[][]For printing of spectrum, click File  “Print preview”. Select respective necessary template and then print

Calibration:

[][]Calibrate the FTIR Spectrophotometer at 6 month’s frequency either by following procedure or as per supplier’s protocol:
[][]Power ON the Spectrometer. Wait for at least 1 hour. Power ON PC & Printer.
[][]Double click on “IRsolution” software icon. Press Measure
[][]Select FTIR Parameters in parameter window as follows:
[][]Data :
[][]Measurement Mode: % Transmitance ,
[][]Resolution : 2
[][]Apodization : Happ-Genzel
[][]No of Scans : 10
[][]Range (cm-1) : Min : 400 cm-1 Max : 4000 cm-1
[][]Instrument :
[][]Beam : Internal
[][]Detector : Standard
[][]Mirror speed : 2.8
[][]More :
[][]Mode : Power
[][]Remove sample, if any, from the sample compartment.
[][]Click on Measurement then “Initialize” then “Yes”.
[][]After successful initialization, click BKG then “OK”. Wait till window on the screen is displayed as last Bkg.
[][]After ‘Bkg scan’, place the Polystyrene film in the sample chamber and close the chamber.
[][]Enter the Polystyrene 1 and Wave number verification in comment box and enter the data file location in Data file box.
[][]Click Sample to scan the polystyrene film (0.05 mm thick). Wait till the actual sample IR scan is displayed.
[][]Click on the spectrum window. Select Calculate  peak table. Type threshold: 65.00.
[][]Click on Calc  OK
[][]For printing of spectrum, click File  “Print preview”. Select respective necessary template and then print. Collect Polystyrene spectrum and peak table printed in two pages.

Limit of Wave Number Accuracy

[][]Check the maximum at following wave numbers (cm-1): 3060.0 (±1.5) cm-1, 2849.5 (±1.5) cm-1, 1942.9 (±1.5) cm-1, 1601.2 (±1.0) cm-1, 1583.0 (±1.0) cm-1, 1154.5 (±1.0) cm-1, 1028.3 (±1.0) cm-1.
[][]Resolution of apparatus
[][]Resolution due to transmittance:
[][]Record the Spectrum of a polystyrene film of approximately 35 µm thickness using Measuring Mode: % T.
[][]Measure the percentage transmittance at the transmission maximum at 2870 cm-1 (3.48 µm) and that at the transmission minimum at 2849.5 cm-1 (3.51 µm).
[][]Measure the percentage transmittance at the transmission maximum at 1589 cm-1 (6.29 µm) and that at the transmission minimum at 1583 cm-1 (6.32 µm).
[][]Record the results in calibration information sheet as per Annexure-I.

Acceptance criteria:

[][]The difference between the % transmittance at the transmission maximum at 2870 cm-1 (3.48 µm) and that at the transmission minimum at 2849.5 cm-1 (3.51 µm) must be greater than 18.
[][]The difference between the percentage transmittance at the transmission maximum at 1589 cm-1 (6.29 µm) and that at the transmission minimum at 1583 cm-1 (6.32 µm) must be greater than 10.

Resolution due to Absorbance:

[][]Record the Spectrum of a polystyrene film of approximately 35 µm thickness using Measuring Mode: Abs.
[][]Measure the absorbance at the absorption minimum at 2870 cm-1 and the absorption maximum at 2849.5 cm-1.
[][]Measure the absorbance at the absorption minimum at 1589 cm-1 and the absorption maximum at 1583 cm-1.
[][]Record the results in calibration information sheet as per Annexure-I.

Acceptance criteria:

[][]The difference between the absorbance at the absorption minimum at 2870 cm-1 and the absorption maximum at 2849.5 cm-1 is greater than 0.33.
[][]The difference between the absorbance at the absorption minimum at 1589 cm-1 and the absorption maximum at 1583 cm-1 is greater than 0.08.
[][]If the calibration is not within the specified standards, check the cleanliness of polystyrene film again and repeat the calibration.
Wavelength Repeatability Test:
[][]Repeat the Spectrum of the polystyrene film and Superimposed one after another of the absorption bands at 2849.5 cm–1 (3.51 µm), 1601.2 cm–1 (6.25 µm), 1028.3 cm –1 (9.72 µm).
[][]Acceptance Criteria: Compare the difference within 0.5% of the wave number scale and Purity index should be within 0.9500 – 1.0000
[][]Affix the label “CALIBRATED “on the equipment if all results are satisfactory. If the equipment found out of calibration limit affix “NOT FIT FOR USE” label and inform supplier.

Cleaning procedure:

[][]Clean the instrument with clean dry cloth daily.
[][]Remove your sample from the ATR, by using a cloth that is damped with acetone.
[][]Clean the plunger in the same way, if it made contact with sample.
[][]Never squirt (spray) acetone directly on the platform.

Annexure: Calibration of FTIR

Annexure-I: Calibration Information Sheet for FTIR Spectrophotometer
Annexure-II: Operation Logbook for FTIR Spectrophotometer

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Electric Analytical Balance Calibration, Cleaning & Daily Accuracy Check

Electric Analytical Balance Calibration; Purpose :

Electric Analytical Balance Calibration; The purpose of this SOP is to describe the operation, calibration, cleaning and daily accuracy check of Electric Analytical Balance

Scope :

This procedure is applicable for Electric Analytical Balance , installed in the quality control laboratory of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure
[][]QC: Quality Control

Responsibilities:

Executive/Sr. Executive, QC

[][]To ensure that this procedure is followed.
[][]To ensure daily accuracy check of the balances.
[][]To maintain the records properly as per SOP.
[][]To preserve calibration, daily accuracy check record.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]Arrange training on the SOP to all concerned personnel.
[][]To ensure implementation of the SOP after training.

Head of Quality Assurance

[][]Approval of the SOP
[][]To ensure the overall implementation of the SOP.

Procedure:

General precautions:

[][]Do not move or replace Balance after calibration. If require, calibrate after movement.
[][]Do not place Balance near to heat generating equipment or direct sunlight.
[][]Clean up any spillage in or around the balance immediately after operations.
[][]Proper protective clothing such as safety glasses, gloves and Laboratory coat must be worn during weighing process.
[][]Do not use sharply pointed objects to operate the keyboard of balance.
[][]Do not use cleaning agents which contain solvents or abrasive ingredients.

Operation:

To start up:

[][]Level and adjust at each time it is moved to a new location. The balance is exactly horizontal when the air bubble is in the middle of the level glass. Adjust the two front leveling feet appropriately until the air bubble comes to rest exactly in the middle of the glass.
[][]Plug the AC adapter and connect the power supply. Connect the printer to the balance.
[][]Switch on the printer using I/O switch.
[][]Press On/Off () button to on the Electric Analytical Balance. Display will show 0.0000g.
[][]Convert the weighing unit from g into mg, press scroll down button if necessary.
[][]Allow the balance to warm up to enable it to adapt itself to the ambient condition.
[][]Long press for menu button and select ‘BASIC’ by single press Enter button
[][]Set date, time and unit using keys and Enter button and save the settings using button.
[][]Press cancel (C) button to return come out of that ‘BASIC’ option and return to its main menu

Weighing:

[][]Check the machine is clean and calibrated. Then remove all loads from weighing pan.
[][]When zero (0.0000 g) reading is displayed, the balance is ready for operation. If the display shows greater than or less than zero, press tare button to tare the balance.
[][]If the balance is not in the weighing mode, press and hold the key down until ‘WEIGHING’ in the display.
[][]Use handle/coupling element for the operation of the draft shield door of the both side of the instrument.
[][]Open right/left/upper sliding window of the instrument.
[][]Place empty container/weighing paper on the pan of the balance. Close the sliding window.
[][]The weight is displayed. Allow the reading to stabilize and wait until the instability detector disappears from the left side of the display and the stability beep sounds.
[][]Press Tare button to tare the balance. When zero (0.0000 g) reading is displayed, the balance is ready for weighing.
[][]The weighing-in aid is a dynamic graphic indicator which shows the used amount of the total weighing range. It can be recognized at a glance when the load on the balance approaches the maximum load.
[][]Add weighing sample (Maximum 120 g) on the container/weighing paper using weighing spoon. Close the sliding window. The net weight is now displayed.
[][]Allow the reading to stabilize and wait until the instability detector (O) disappears from the left side of the display and the stability beep sounds
[][]To get printout of the weight, press print button.
[][]For performing another weighing press Tare button to tare the balance and follow previous steps from to increase or decrease digit, press display resolution button.
[][]Finally, press and hold On/Off button button untill ‘SHUT OFF’ shows on the display.
[][]Fill up the Operation Log book for Semi-Micro Balance (as per Annexure-II).

Daily Accuracy Check:

[][]Perform the Internal and External Calibration as per below mentioned procedure
[][]Take 20 g, 70 g of certified weight and clean it with a soft cloth.
[][]Use tare button to tare the balance before start with a weighing.
[][]Always press button to tare the balance between the interval of one weight to another and observe whether the instability detector (O) disappears from the left side of the display or not and the balance will give a stability beep sounds.
[][]Open one sliding window and place the weights separately at the center of the weighing pan, close the sliding window and allow the reading to be stabilized and wait until the instability detector (O) disappear from the left side of the display and the stability beep sounds.
[][]Print the results by pressing print button if necessary.
[][]Record the value of those weights in Log Book for Daily Accuracy Check (as per Annexure-I).

Calibration:

Internal Calibration:
Manual Adjustment with Internal weight:

[][]Long press menu button and press scroll down button to go to ‘ADVANCED’ option.
[][]Select ‘ADVANCED’ by pressing Enter button.
[][]Press scroll down button once to select ‘CAL’ option by pressing Enter button.
[][]Then select ‘ADJ. INT’ using scroll down button and then press Enter button.
[][]Press Cancel (C) twice and save the settings if required by scrolling down button and press Enter button and then return to its main menu.
[][]Unload weighing pan Press and hold calibration button to execute ‘Internal Adjustment’.
[][]The balance adjusts itself automatically. The adjusting is finished when the message “ADJ.DONE” appears briefly on the display. The balance returns to the last active application and is ready for operation.
[][]After adjustment, the result of the calibration will be printed out automatically or press print (button for print copy.

External Calibration:

Manual Adjustment with External weight:

[][]Long press menu button and press scroll down button to go to ‘ADVANCED’ option.
[][]Select ‘ADVANCED’ by pressing Enter button.
[][]Press scroll down button once to select ‘CAL’ option by pressing Enter button.
[][]Select ‘ADJ. EXT’ by using scroll down and then press Enter button.
[][]Set the adjustment weight (100g) by using -/+ key for External Calibration and press Enter button.
[][]Then press cancel (C) button twice and save the settings if required by using -/+ key and press Enter button and then return to its main menu.
[][]Unload weighing pan Press and hold calibration button to execute ‘External Adjustment’.
[][]The required predefined adjustment weight value flashes on the display.
[][]Place adjustment certified weight on the center of pan. The balance adjusts itself automatically.
[][]When ‘0.0000 g’ flashes, remove the adjustment weight.
[][]The adjustment is finished when the message ‘ADJ DONE’ appears briefly on the display. The balance returns to the last active application and is ready for operation.
[][]After adjustment, the result of the calibration will be printed out automatically or press print button for print copy.

Eccentricity:

[][]Take 20 g, 70 g of certified weight and clean it with a soft cloth.
[][]Use tare button to tare the balance before start with a weighing.
[][]Always press button to tare the balance between the interval of one weight to another and observe whether the instability detector (O) disappears from the left side of the display or not and the balance will give a stability beep sounds.
[][]Place 50g weight at center, Left Rear, Right Rear, right Front, Left Front and center on the pan again separately.
[][]Allow the reading to be stabilized in each time while weighing and wait until the instability detector (O) disappear from the left side of the display and the stability beep sounds.
[][]Press print button separately to print each individual reading in same print page.

Linearity:

[][]Use Tare button to tare the balance before start with a weighing.
[][]Always press button to tare the balance between the interval of one weight to another and observe whether the instability detector (O) disappears from the left side of the display or not and the balance will give a stability beep sounds.
[][]Place 10 g, 20 g and 50 g on the center of pan separately.
[][]Allow the reading to be stabilized in each time while weighing and wait until the instability detector (O) disappear from the left side of the display and the stability beep sounds.
[][]Press Print ( ) button separately to print each individual reading in same print page.

Sensitivity:

[][]Use Tare button to tare the balance before start with a weighing.
[][]Always press button to tare the balance between the interval of one weight to another and observe whether the instability detector (O) disappears from the left side of the display or not and the balance will give a stability beep sounds.
[][]Place 100 g on the center of pan.
[][]Allow the reading to be stabilized in each time while weighing and wait until the instability detector (O) disappear from the left side of the display and the stability beep sounds.
[][]Press Print ( ) button separately to print each individual reading in same print page.

Repeatability:

[][]Use Tare button to tare the balance before start with a weighing.
[][]Always press button to tare the balance between the interval of one weight to another and observe whether the instability detector (O) disappears from the left side of the display or not and the balance will give a stability beep sounds.
[][]Place 100 g on the center of the pan for ten times separately.
[][]Allow the reading to be stabilized in each time while weighing and wait until the instability detector (O) disappear from the left side of the display and the stability beep sounds.
[][]Press Print ( ) button separately to print each individual reading in same print page.

Result:

[][]Record all the values for calibration in Calibration Information Sheet for Electric Analytical Balance (as per Annexure-III).
[][]Perform the Calibration of the Electric Analytical Balance once after every six months.

Cleaning:

[][]Ensure that no liquid comes into contact with the balance and AC adapter.
[][]Remove all objects from the balance.
[][]Clean the pan with soft brush followed by with soft clean cloth.
[][]Clean all of the parts of the balance with clean dry cloth.
[][]Set the parts of weighing pan carefully.

 

Annexure:

Annexure-I: Log book for Daily Accuracy Check of Electric Analytical Balance
Annexure-II: Operation Log book for Electric Analytical Balance
Annexure-II: Calibration Information Sheet for Electric Analytical Balance

Electric Analytical Balance Calibration, Cleaning & Daily Accuracy Check Read More »

Calibration of Semi-Micro Balance

Calibration of Semi-Micro Balance; Purpose :

Calibration of Semi-Micro Balance; The purpose of this SOP is to describe the operation, calibration, cleaning and daily accuracy check of Semi-Micro Balance (Model: MS205DU).

Scope :

This procedure is applicable for Semi-Micro Balance (Model: MS205DU), installed in the quality control laboratory of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure
[][]QC: Quality Control

Responsibilities:

Executive/Sr. Executive, QC

[][]To ensure that this procedure is followed.
[][]To ensure daily accuracy check of the balances.
[][]To maintain the records properly as per SOP.
[][]To preserve calibration, daily accuracy check record.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]Arrange training on the SOP to all concerned personnel.
[][]To ensure implementation of the SOP after training.

Head of Quality Assurance

[][]Approval of the SOP
[][]To ensure the overall implementation of the SOP.

Procedure:

General precautions:

[][]Do not move or replace Balance after calibration. If require, calibrate after movement.
[][]Do not place Balance near to heat generating equipment or direct sunlight.
[][]Clean up any spillage in or around the balance immediately after operations.
[][]Proper protective clothing such as safety glasses, gloves and Laboratory coat must be worn during weighing process.
[][]Do not use sharply pointed objects to operate the keyboard of balance.
[][]Do not use cleaning agents which contain solvents or abrasive ingredients.

Calibration of Semi-Micro Balance; Operation:

To start up:

[][]Level and adjust at each time it is moved to a new location. The balance is exactly horizontal when the air bubble is in the middle of the level glass. Adjust the two front leveling feet appropriately until the air bubble comes to rest exactly in the middle of the glass.

[][]Plug the AC adapter and connect the power supply. Connect the printer to the balance.
[][]Switch on the printer using I/O switch.

[][]Press On/Off button to on the Semi-Micro Balance. Display will show 0.00000 g.
[][]Convert the weighing unit from g into mg, press scroll down button if necessary.
[][]Allow the balance to warm up to enable it to adapt itself to the ambient condition.
[][]Press menu button and select ‘BASIC’ by pressing Enter button
[][]Set date, time and unit using -/+ keys and Enter button and save the settings.
[][]Press cancel (C) button to return come out of that ‘BASIC’ option and return to its main menu.
[][]Perform the daily accuracy check at the starting of the day.

Calibration of Semi-Micro Balance; Weighing:

[][]Check the machine is clean and calibrated. Then remove all loads from weighing pan.
[][]When zero (0.00000 g) reading is displayed, the balance is ready for operation. If the display shows greater than or less than zero, press Tare button to tare the balance.
[][]If the balance is not in the weighing mode, press and hold the key down until ‘WEIGHING’ in the display.
[][]Use handle/coupling element for the operation of the draft shield door of the both side of the instrument.
[][]Open right/left/upper sliding window of the instrument.
[][]Place empty container/weighing paper on the pan of the balance. Close the sliding window.
[][]The weight is displayed. Allow the reading to stabilize and wait until the instability detector (O) disappears from the left side of the display and the stability beep sounds.

[][]Press Tare button to tare the balance. When zero (0.00000 g) reading is displayed, the balance is ready for weighing.
[][]The weighing-in aid is a dynamic graphic indicator which shows the used amount of the total weighing range. It can be recognized at a glance when the load on the balance approaches the maximum load.
[][]Add weighing sample (Maximum 220 g) on the container/weighing paper using weighing spoon. Close the sliding window. The net weight is now displayed.
[][]Allow the reading to stabilize and wait until the instability detector disappears from the left side of the display and the stability beep sounds
[][]To get printout of the weight, press print button.

[][]For performing another weighing press tare (O/T) button to tare the balance and follow all steps described above. To increase or decrease digit, press display resolution button.

[][]Finally, press and hold On/Off button ( ) button until ‘SHUT OFF’ shows on the display.
[][]Fill up the Operation Log book for Semi-Micro Balance (as per Annexure-II).

Daily Accuracy Check:

[][]Perform the Internal and External Calibration as per below mention Steps under Calibration.
[][]Take 50 g, 150 g of certified weight and clean it with a soft cloth.
[][]Use tare button to tare the balance before start with a weighing.
[][]Always press button to tare the balance between the interval of one weight to another and observe whether the instability detector (O) disappears from the left side of the display or not and the balance will give a stability beep sounds.
[][]Open one sliding window and place the weights separately at the Centre of the weighing pan, close the sliding window and allow the reading to be stabilized and wait until the instability detector (O) disappear from the left side of the display and the stability beep sounds.
[][]Print the results by pressing print button if necessary.
[][]Record the value of those weights in Log Book for Daily Accuracy Check (as per Annexure-I).

Calibration:

Internal Calibration:

Manual Adjustment with Internal weight:

[][]Press menu button and then press scroll down to go to ‘ADVANCED’ option.
[][]Select ‘ADVANCED’ by pressing Enter button.
[][]Press scroll down button once to select ‘CAL’ option by pressing Enter button.
[][]Then select ‘ADJ. INT’ using scroll down button and then press Enter button.
[][]Press cancel (C) twice and save the settings if required by scrolling down button and press Enter button and then return to its main menu.
[][]Unload weighing pan Press and hold calibration button to execute ‘Internal Adjustment’.
[][]The balance adjusts itself automatically. The adjusting is finished when the message “ADJ.DONE” appears briefly on the display. The balance returns to the last active application and is ready for operation.
[][]After adjustment, the result of the calibration will be printed out automatically.

External Calibration:

Manual Adjustment with External weight:

[][]Follow the previous instruction[Manual Adjustment with Internal weight] for manual adjustment.
[][]Select ‘ADJ. EXT’ by using scroll down and then press Enter button.
[][]Enter the adjustment weight (200g) by using -/+ key for External Calibration and press Enter button.
[][]Then press cancel (C) button twice and save the settings if required by scrolling down button and press Enter button and then return to its main menu.
[][]Unload weighing pan Press and hold calibration button to execute ‘External Adjustment’.
[][]The required predefined adjustment weight value flashes on the display.
[][]Place adjustment certified weight on the center of pan. The balance adjusts itself automatically.
[][]When ‘0.0000 g’ flashes, remove the adjustment weight.
[][]The adjustment is finished when the message ‘ADJ DONE’ appears briefly on the display. The balance returns to the last active application and is ready for operation.

Eccentricity:

[][]Take 50 g, 150 g of certified weight and clean it with a soft cloth.
[][]Use Tare button to tare the balance before start with a weighing.
[][]Always Press button to tare the balance between the interval of one weight to another and observe whether the instability detector (O) disappears from the left side of the display or not and the balance will give a stability beep sounds.
[][]Place 100 g weight at center, Left Rear, Right Rear, right Front, Left Front and center on the pan again separately.
[][]Allow the reading to be stabilized in each time while weighing and wait until the instability detector disappear from the left side of the display and the stability beep sounds.
[][]Press print button separately to print each individual reading in same print page.

Linearity:

[][]Take 50 g, 150 g of certified weight and clean it with a soft cloth.
[][]Use tare button to tare the balance before start with a weighing.
[][]Always press button to tare the balance between the interval of one weight to another and observe whether the instability detector disappears from the left side of the display or not and the balance will give a stability beep sounds.
[][]Place 20 g, 50 g, 100 g, and 200 g on the center of pan separately.
[][]Allow the reading to be stabilized in each time while weighing and wait until the instability detector (O) disappear from the left side of the display and the stability beep sounds.
[][]Press Print button separately to print each individual reading in same print page.

Sensitivity

[][]Take 50 g, 150 g of certified weight and clean it with a soft cloth.
[][]Use tare button to tare the balance before start with a weighing.
[][]Always press button to tare the balance between the interval of one weight to another and observe whether the instability detector disappears from the left side of the display or not and the balance will give a stability beep sounds.
[][]Place 200 g on the center of pan.
[][]Allow the reading to be stabilized in each time while weighing and wait until the instability detector (O) disappear from the left side of the display and the stability beep sounds.
[][]Press Print button separately to print each individual reading in same print page.

Repeatability (200 g):

[][]Take 50 g, 150 g of certified weight and clean it with a soft cloth.
[][]Use tare button to tare the balance before start with a weighing.
[][]Always press button to tare the balance between the interval of one weight to another and observe whether the instability detector disappears from the left side of the display or not and the balance will give a stability beep sounds.
[][]Place 200 g on the center of the pan for ten times separately.
[][]Allow the reading to be stabilized in each time while weighing and wait until the instability detector (O) disappear from the left side of the display and the stability beep sounds.
[][]Press Print button separately to print each individual reading in same print page.

Repeatability (20 g):

[][]Take 50 g, 150 g of certified weight and clean it with a soft cloth.
[][]Use tare button to tare the balance before start with a weighing.
[][]Always press button to tare the balance between the interval of one weight to another and observe whether the instability detector disappears from the left side of the display or not and the balance will give a stability beep sounds.
[][]Place 20 g on the center of the pan for ten times separately.
[][]Allow the reading to be stabilized in each time while weighing and wait until the instability detector (O) disappear from the left side of the display and the stability beep sounds.
[][]Press Print button separately to print each individual reading in same print page.

Result:

[][]Record all the values for calibration in Calibration Information Sheet for Semi-Micro balance (as per Annexure-III).
[][]Perform the Calibration of the Semi-Micro Balance once in every six months.

Cleaning:

[][]Ensure that no liquid comes into contact with the balance and AC adapter.
[][]Remove all objects from the balance.
[][]Clean the pan with soft brush followed by with soft clean cloth.
[][]Clean all of the parts of the balance with clean dry cloth.
[][]Set the parts of weighing pan carefully.

Annexure:

Annexure-I: Log book for Daily Accuracy Check of Semi-Micro Balance
Annexure-II: Operation Log book for Semi-Micro Balance
Annexure-II: Calibration Information Sheet for Semi-Micro balance

Calibration of Semi-Micro Balance Read More »

Maintenance of Desiccator

Maintenance of Desiccator; Purpose :

Maintenance of Desiccator; The purpose of this procedure is to describe the maintenance (handling and cleaning) of desiccator.

Scope :

This procedure is applicable for all desiccators in the quality control laboratory of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

Desiccant canister: A container with hygroscopic substance which induces or sustains a state of dryness in its area.

Responsibilities:

Officer/ Executive, QC

[][] To follow the instructions of this procedure correctly.

Sr. Executive, QC

[][] To ensure that SOP is followed correctly.

Manager, Quality Control

[][] To ensure that this procedure is kept up to date.
[][] To ensure appropriate personnel from the section are trained on this procedure.
[][] To confirm that SOP is technically sound and reflects the required working practices.

Manager, Quality Assurance

[][]Approval of the SOP.
[][]To ensure the overall implementation of the SOP.

Procedure:

Precaution(s):

[][]Do not touch hot samples, while transferring them from Oven/Muffle furnace to desiccator.

Operation

[][]Place about 200 g of silica (desiccant) and/or dessicant canister into the bottom of the desiccator.
[][]Set the sample platform (desiccator plate) to the desiccator.
[][]Apply a smear of grease in between lid & desiccator rim to avoid sticking of lid with the dessicator.
[][]Close the lid properly.
[][]Open the lid to retain the sample to be analyzed and close the lid again.
[][]Remove the sample after required period of time.

Cleaning

[][]Rub the desiccator, sample platform (desiccator plate) and lid with a dry, clean cloth.
[][]Laboratory Attendant will collect the silica (desiccant) to activate (in the oven at about 105°C) and then replace it to the desiccator once in a week or even more frequently when blue color of desiccant turns purple/pink.
[][]Fill up the logbook for desiccant change (as per Annexure-I).
[][]Officer/Executive, QC will check the logbook for proper condition of desiccant or the desiccant change.

Annexure:

Annexure-I: Logbook for desiccant change of desiccator.

Maintenance of Desiccator Read More »

Handling of Reference Standard and Preparation & Storage of WS

Handling of Reference Standard; Purpose :

Handling of Reference Standard; The purpose of this procedure is to provide the instruction for handling of reference standard, impurity standards and standardization & storage of working standard.

Scope :

This procedure is applicable for the management of reference standard and working standard in the quality control laboratory of general block of XX Pharmaceuticals Ltd.

Definitions/Abbreviation:

Chemical Reference Standard:

Primary chemical reference standard is one that is widely acknowledged to have the appropriate qualities within a specified context, and whose value is accepted without requiring comparison to another chemical standard.

Secondary Reference Standard/Working Standard:

A secondary chemical reference standard is a substance whose characteristics are assigned and/or calibrated by comparison with a primary chemical reference standard. The extent of characterization and testing of a secondary chemical reference standard may be less than for a primary chemical reference standard.

[] CRS : Chemical Reference Standard
[] WS : Working Standard
[] USPRS : United States Pharmacopeia Reference Standard
[] BPCRS : British Pharmacopeia Chemical Reference standard
[] ICRS : International Chemical Reference Standard (WHO)
[] EPCRS: European Pharmacopeia Chemical Reference Standard

Responsibilities:

Officer/Executive, Quality Control

[] Handle reference standard properly according to manufacturer’s certificate of analysis and instruction.
[] To standardize working standard
[] ollow the instructions of this procedure correctly.

Sr. Executive, QC

[] To ensure proper handling & storage of reference standard andworking standard.
[] To keep a track of its use, use before date, current pharmacopoeias reference standard lot number and all the related documents.

Manager, Quality Control

[] To approve WS after verification.
[] To ensure appropriate personnel from the section are trained on this procedure.
[] To confirm that SOP is technically sound and reflects the required working practices.

Head of Quality Assurance

[] To ensure the overall implementation of the SOP.
[] Approval of the SOP.

Procedure:

General Note:

[] Read carefully the label of container before use of CRS.
[] After use sealed properly the CRS.
[] Handle the CRS according to material safety data sheet.
[] Ensure proper storage of CRS and WS.
[] Do not use CRS and WS after expiry.

Handling of Reference Standard:

Use one of the following Reference Standard for analysis of raw materials:
[] Pharmacopoeia Standards
[] Validated Suppliers Standards
[] In-house Reference Standards
[] Ensure that the purity of CRS is equivalent to 99.5% or higher, calculated on the basis of the material in its anhydrous form or free of volatile substances.
[] After receiving of CRS, write down the details in Chemical Reference Standard Details Record (as per Annexure-I).

[]During receiving, check the following points :

[][] Sealing condition (flip off seal for USPRS)
[][] Label on the container
[][] Part No.
[][] Lot No.
[][] Certificate of Analysis with complete information on test method.
[][] Information on optimal storage condition (Temperature and humidity).
[][] Updated material safety data sheet outlining any health hazard associated with the material.

[]Match the lot number of CRS with supplied vial.
[]Preserve all reference standard at 2-80C or according to the label of the container or according to manufacturer’s instruction.
[]Preserve all CRS up to expiry date.

[]Standardization of Working standard:

Determination of Identification:

[][]Use CRS for material identification by IR spectrometry and/or chromatographic methods.
[][]For identification, select a lot of respective raw material, which has been approved recently.
[][]Follow the approved analytical method for identification.
[][]Analyze the physical and chemical test against the reference standard.
[][]Confirm that the result is within specification and prepare the test report in Working Standard Analysis Report (as per Annexure-II).
[][]Use this lot as WS for the next routine analysis.

[]Determination of Assay:

[][]For standardization of WS, select a lot of respective raw material, which has been approved recently.
[][]Standardize this lot against the reference standard.
[][]Perform Water (by KF)/Loss on drying (whichever applicable) in twice as per specification and validated analytical method. The average of two results shall be used to determine the assay value.
[][]If the assay is performed by HPLC inject a blank, five replicate injection of standard solution, one test solution & one end standard. If the assay is performed by UV-Spectrophotometer or Potentiometer, at least analysis two samples. Percent of RSD for peak areas or readings of individual analyses should not be more than 1.0%.
[][]The content should be declared to two digits after decimal point.
[][]Prepare the report in Working Standard Analysis Report as per Annexure-II.
[][]Keep all relevant certificates of analysis, IR spectrum, chromatogram and any data regarding identification, purity and assay.
[][]A history sheet of each Working standards shall be maintained in Working Standard Preparation & Consumption Record (as per Annexure –III).

[]Labeling & Storage of Working Standard:

[][]After analysis kept sample in properly sealed clean and dry amber coloured glass vials/bottles.
[][]Prepare four vials/bottles of each working standard containing about 5 g.
[][]Prepare six vials/bottles of each working standard containing about 4 g in case of moisture sensitive materials.
[][]Affix the label on the WS Vials/bottles as per Annexure IV.
[][]On the opening of the vials/bottles, mention the date of opening on label.
[][]In order to maintain the integrity of the working standard, the dispensed vials/bottles have to be kept at the conditions indicated on the vials/bottles label. If the storage condition is 2ºC to 8ºC, store the dispensed vials/bottles in refrigerator with controlled temperature monitoring system and if the storage condition is recommended as room temperature, store the vials/bottles in a desiccator

[]Validity/Shelf Life and Consumption of Working Standard:

[][]Before preparation of working standard ensures that the manufacturer’s shelf life of respective material is valid up to more than one year.
[][]Use the working standard within one year from the date of standardization.
[][]Use the working standard of moisture sensitive material within two months from the date of opening.
[][]Use the working standard of non moisture sensitive materials within three months from the date of opening.
[][]Before use, keep refrigerated vials in a desiccator to reach at room temperature. After use seal the vial/bottle properly and store as per recommended storage condition.

[]Reference numbering system of Working standard:

[][]Assign working standard reference number in following way:
[][]Put first two letters of working standard i.e. WS.
[][]Put a hyphen (-) after the abbreviation, then a serial number of four digits i.e. 0001, again put a slash and then two digits of month i.e. 01 for January.
[][]Again put a slash (/) and then last two digits of the year i.e. XX for year 20XX.
[][]For example, First working standard prepare on January 20XX will get the Lab. Control No. WS-0001/01/XX

Discard Procedure of CRS & WS:

[][]At the time of issuing a new vial/bottle, the old/used vial/bottle shall be destroyed in following manner:
[][]Empty the contents in waste beaker containing previously prepared 0.4% sodium hypochlorite solution. Shake the dispersion of sample in container with the help of a glass rod and leave it for at least 12 hours. Then neutralize the liquid (pH 6-9) by acid/alkali and dilute the liquid 10 to 20% by fresh water and drain out slowly into designated place and clean the drain with adequate water flushing.
[][]Deface the label of the vial/bottle.
[][]Discard the vial/bottle into the specific container as broken glassware. Record the destruction details in Chemical Reference Details Record (as per Annexure-I) for CRS, and Working Standard Preparation & Consumption Record for WS (as per Annexure-III).

Annexure:

Annexure-I: Chemical Reference Standard Details Record
Annexure-II: Working Standard Analysis Report
Annexure-III: Working Standard Preparation & Consumption Record
Annexure-IV: Label of Working Standard

Handling of Reference Standard and Preparation & Storage of WS Read More »

Calibration of Glassware with Handling & Washing

Calibration of Glassware: Purpose

Calibration of Glassware; The purpose of this SOP is to ensure that all glass wares are properly handled, thoroughly cleaned and calibrated accurately before use.

Scope:

This procedure is applicable for glassware handling, washing and calibration used in the different analysis of quality control laboratory and microbiology laboratory of general block of XX Pharmaceuticals Ltd.

Definitions/Abbreviation:

[] ASTM: American Society for Testing and Materials
[] SOP   : Standard Operating Procedure

Responsibilities:

[] Officer/Executive/Sr. Executive, Quality Control
[] To ensure that this procedure is followed.
[] To maintain the records properly as per SOP.

Manager, Quality Control

[] To ensure that this procedure is kept up to date.
[] To confirm that the SOP is technically sound and reflects the required working practices.
[] To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.
[] Schedule calibration of the instrument at the defined intervals.

Head of Quality Assurance

[] Approval of the SOP.
[] To ensure the overall implementation of the SOP.

Procedure:

Precaution(s):

[] Handle with care during cleaning of Glassware.
[] Before discard of glassware, observe the label on glassware and handle with care as the type of chemical.
[] Wear gloves, mask and protective clothing during glassware handling and cleaning.
[] Do not use laboratory glassware for drinking purpose.
[] Do not handle the hot glassware without heat resistant gloves.
[] Do not put the hot glassware on cold or wet surface or cold glassware on hot surface.
[] Avoid to heat glassware that is etched, cracked, chipped, nicked or scratched.
[] Do not heat directly thin glassware with flaming.
[] Never place the glassware from the freezer into warm water baths.

Handling Procedure:

[] Hold the beakers, bottles, flask the side and bottoms rather than by the tops.
[] Avoid over tighten the clumps.
[] Use always coated clumps to avoid breakage while the clumping glassware.
[] Cool the glassware slowly to prevent breakage.
[] Dispose the broken glass into specific waste bucket.
[] Keep all cleaned glassware at designated place.

Washing Procedure:

[] Transfer all used glassware to washing area.
[] Discard the solution from glassware into a designated container/place.
[] Rinse initially all glassware with sufficient potable water for removal the residual content of solution.
[] For pipette, pass sufficient potable water through the pipette by force at two or three times.
[] Wipe to remove the label with detergent powder or suitable solution.
[] Allow to soak the glassware with diluted detergent for 10-15 minutes to remove any contaminants.
[] Rinse the glassware with sufficient potable water until detergent is removed.
[] Finally rinse with purified water for two or three times for removal any contaminating substances that may be present in the potable water.
[] Discard the rinsing solution.
[] Place cleaned glassware into Glassware drying rack for removal of residual water from glassware.
[] Dry the glassware for QC analysis and sterilize the glassware at 200°C for 1 hour for use in Microbiological analysis.

Calibration Procedure:

Burette Calibration:

[] Take a burette and inspect to ensure smooth tap operation.
[] Observe the tip of the burette, ensure no cracks or chips.
[] Observe markings on burette which is legible.
[] Rinse the burette at several times with purified water.
[] Fill the glassware up to the mark.
[] Dispense into a pre-tarred 100 ml beaker.
[] Record final volume.
[] Record mass of water.
[] Repeat the same procedure for another two times.
[] Calculate the volume delivered from the equation below using recoded weight and density of water at the temperature of calibration.  Take Tabulated Density of water at the temperature of calibration from the Annexure-II.
Volume of Burette= Weight/Tabulated Density of water at the temperature of calibration
[] Record calculated volumes, determine mean and compare the volume with that read from the burette and then determine the error as per Annexure – I.

Limit of error of the calculated volume should be as per following table (as per ASTM E-287)
Nominal Volume, mL2550
Limit of error, mL0.030.03
Limit of error, %0.120.10

Calibration of Pipette:

[] Take purified water into a beaker.
[] Record the temperature of the water used.
[] Weigh and tare another 100 ml beaker.
[] Dispense water as per pipette volume into tarred beaker.
[] Record the weight of purified water.
[] Repeat the same procedure for another two times.
[] Calculate the volume delivered from the equation below using recoded weight and density of water at the temperature of calibration.  Take Tabulated Density of water at the temperature of calibration from the Annexure-II.
Volume of Pipette= Weight/Tabulated Density of water at the temperature of calibration
[] Record calculated volumes, determine mean and compare the volume with the nominal volume and then determine the error as per Annexure – I.

Limit of error of the calculated volume should be as per following table (as per ASTM E-969)-
Nominal Volume, mL1234510152025
Limit of error, mL0.0060.0060.010.010.010.020.030.030.03
Limit of error, %0.600.300.330.250.200.200.200.150.12

Calibration of Volumetric Flask:

[] Observe the volumetric flask, ensure no cracks or chips.
[] Observe markings on volumetric flask, ensure they are legible.
[] Rinse volumetric flask at several times with purified water.
[] Rinse with acetone and air dry.
[] Tare volumetric flask on balance.
[] Add purified water and fill to mark.
[] Record weight of water.
[] Record the temperature of the water used.
[] Repeat the same procedure  for another two times
[] Calculate the volume delivered from the equation below using recoded weight and density of water at the temperature of calibration.  Take Tabulated Density of water at the temperature of calibration from the Annexure-II.

[] [] Volume of Volumetric Flask= Weight/   Tabulated Density of water at the temperature of calibration

Record calculated volumes, determine mean and compare the volume with the nominal volume and then determine the error as per Annexure – I.

Limit of error of the calculated volume should be as per following table (as per ASTM E-288)
Nominal Volume, mL
510255010020025050010002000
Limit of error, mL0.020.020.030.050.080.100.120.150.300.50
Limit of error, %0.400.200.120.100.080.050.050.030.030.025

Download All Annexure

Annexure I : Glassware Calibration Record
Annexure II : Density of Water

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Analysis and Release Procedure of Intermediate and Bulk Product

Analysis and Release Procedure: Purpose

Analysis and Release Procedure, The purpose of this procedure is to establish an appropriate system for analysis of intermediate stage sample (i.e. powder, granules, core tablet) and semi-finished (bulk) products (i.e. coated tablet, filled capsule) from production department for ensuring the quality by subsequent testing as well as releasing intermediate stage sample for next processing stage and semi-finished (bulk) products for packaging.

Scope:

This procedure is applicable for intermediate and semi-finished (bulk) products manufactured in general block at XX Pharmaceuticals Limited.

Definitions / Abbreviation:

Standard Operating Procedure (SOP): Standard Operating Procedure.

[] QC: Quality Control.
[] COA: Certificate of Analysis
[] SAF: Sampling Advice Form
[] Mfg. Date: Manufacturing Date
[] Exp. Date: Expiry Date
[] XX: Current version of SOP
[] Bulk Product: Any product which has completed all processing stages up to, but not including, final packaging.
[] Batch (or Lot): A defined quantity of material or product processed in one process or series of processes so that it could be expected to be homogeneous.

Responsibilities:

Sr. Executive/Executive, QC

[] To ensure that the instructions of this procedure are correctly followed.
[] To maintain the records properly as per SOP

Executive, QA

[] To perform sampling.
[] To provide SAF and sample to QC for analysis.
[] To receive report from QC dept. after completion of analysis.

Manager, Quality Control

[] To ensure that this procedure is kept up to date.
[] To confirm that the SOP reflects the required working practices.
[] To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.

Head of Quality Assurance

[] Approval of the SOP.
[] To ensure the overall implementation of the SOP.

Procedure:

General Precaution(s):

[] Check the calibration status of the instruments to be used.
[] Check the validity of the working standard to be used.
[] Do not return any bulk sample to production unit to avoid batch/product mix-up.
[] Transfer excess sample to ‘Sample for Disposal’ place after approval.

Intermediate and Semi-Finished (bulk) Product Test Plan:

[] Before starting analysis ensure the test plan as Annexure-II.
[] In case of ready to fill pellets for capsule, carry out potency calculation by using assay result of representative lot of raw material & average filled weight (taken from in-process result of encapsulation stage). Dissolution test result will be taken from representative lot of raw material.
[] Perform assay & dissolution test in every 10th batch of regular commercial batch and process validation batch in case of ready to fill pellets for capsule.

Receiving and analysis:

[] Executive, Quality Assurance will collect sample of intermediate and semi-finished (bulk) product maintaining the SOP of intermediate and semi-finished (bulk) products sampling procedure.
[] Quality Assurance will provide test sample to QC according to ‘Intermediate and Semi-Finished (bulk) Product Test Plan’ (as per Annexure-II).
[] Executive, Quality Assurance will send test sample along with the Sampling Advice Form (SAF).
[] After receiving the sample, QC Executive will put the Lab. Control No. on the SAF and record all necessary information in ‘Intermediate and Semi-Finished (bulk) Product Log Register’ (as per Annexure-I).
[] After proper entry in the log book, QC Executive will keep the sample in the designated place of ‘Sample Receiving Room’.
[] QC In-charge/Sr. Executive, QC will assign the work and issue the finished product analytical work sheet to QC Sr. Executive/Executive with initial and date on every page and enter the worksheet issued by (initial and date) in the ‘Intermediate and Semi-Finished (bulk) Product Log Register’ (as per Annexure-I).
[] Sr. Executive/Executive, QC will take sample from sample receiving room and test the sample against the respective approved method of analysis.
[] Sr. Executive/Executive, QC will follow ‘Intermediate and Semi-Finished (bulk) Product Test Plan’ (as per Annexure-II) or as per requirement of SAF for analysis.
[] Record all analytical raw data and make calculation in the analyst logbook (Annexure-V) with attachment of required printout of weight(s).
[] Record the results in the work sheet with attachment of required raw data.
[] Carry out the test for assay of single sample preparation.
[] In case of instrumental analysis carried for testing, fill the instrument log properly.
[] Compare the results with the specification.
[] In case where test results go out of specification, report to designated personnel. Analysis may be repeated with proper authorization.

Release:

[] Sr. Executive/Executive, QC will compile the test report and prepare COA (as per Annexure-IV).
[] Sr. Executive/Executive, QC will check the test report, analyst log book, worksheet and COA.
[] In-charge, QC will verify the test report and approve COA if all results comply with the respective specifications.
[] If the test result does not comply with the specification follow the SOP for handling of out of specification.
[] After completion of the test, transfer left over sample in specified place labeled as “Under Test Samples” until the batch is approved.
[] After approval of the batch, transfer the excess sample to a place labeled as “Sample for Disposal” by making necessary entry in sample disposal register.
[] Sr. Executive/Executive, QC will input the necessary data in finished product trend analysis.
[] Send the approved test report with SAF and COA to Quality Assurance.

Find All Annexure Here

Annexure-I     : Intermediate and Semi-Finished (bulk) Product Log Register
Annexure-II    : Intermediate and Semi-Finished (bulk) Product Test Plan
Annexure-III   : Finished Product Analytical Worksheet
Annexure-IV   : Certificate of Analysis
Annexure-V    : Analyst Logbook

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Packaging Material Sampling and Release Procedure

Packaging Material Sampling and Release, Purpose :

The purpose of this SOP is to describe the procedure for sampling and releasing of packaging materials for pharmaceutical products.

Packaging Material Sampling and Release, Scope :

This procedure is applicable for all packaging materials received at the warehouse of  XX Pharmaceuticals Limited.

Definitions/Abbreviation:

[] SOP: Standard Operating Procedure
[] QC: Quality Control
[] GRN: Goods Received Note
[] COA: Certificate of Analysis
[] ERP: Enterprise Resource Planning
[] Sampling: It is a process of collecting the materials so that the collection shall represent the whole lot.
[] Sampling plan: Description of the number of units and/or quantity of material that should be collected.
[] Consignment: A supply of a material of particular batch intended to be used in different department.
[] Lot: A defined quantity of material made by a specified process cycle having uniform quality.

Responsibilities:

The roles and responsibility is as follows:

Officer/Executive/ Sr. Executive, Quality Control

[] To ensure that the procedure is correctly followed.
[] To maintain the records properly as per SOP.
[] To ensure that this procedure is kept up to date.
[] To confirm that the SOP reflects the required working practices.
[] To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.

Executive/ Sr. Executive, Warehouse

[] To ensure availability of containers to be sampled in quarantine area.

Executive, Production

[] To arrange machine trial when required and share the report to QC with the concern of Manager,

Production.

Head of Quality Assurance

[] To ensure the overall implementation of the SOP.
[] Approval of the SOP.

 Procedure:
General Precaution(s):

[] Take sample for microbial testing first followed by other sampling.
[] Sampling should be carried out by trained personnel.

Sampling: Packaging Material Sampling and Release

[] Receive the GRN with Manufacture’s COA from the warehouse and enter the details (GRN no., lab. control no., name of material, code no., invoice/challan no., manufacturer lot no., local batch no., manufactured by, supplied by, pack size, no. of pack, total quantity and received by & date) in the ‘Packaging Material Log Register’ (as per Annexure-I) maintained in QC department for packaging material.
[] Ensure that material is received from Approved Vendor.
[] If the material is not from approved vendor or if the Manufacture’s COA for primary packaging material is not received, inform Supply Chain Management Department.
[] QC Officer/Executive or QC sampler will select the no. of container/packs to be sampled as per sampling plan and sample quantity according to ‘Sampling quantity for Packaging Material’ (as per Annexure-II) and take required no. of “SAMPLED” label.
[] For example, when the total no. of container of inner carton (secondary packaging material) is 25, then no. of container to be sampled will be Ö 25 + 1 = 5 + 1 = 6.
[] If the batch size is 3100 pcs, then 32 pcs of inner cartons will be taken from 6 different containers.

Sampling plan:

[] The n plan

The “n plan” is based on the formula n = 1 + ÖN, where N is the number of sampling units in the consignment. The value of n is obtained by simple rounding. A minimum number of containers needs to be sampled, e.g. if N is less than or equal to 4, then every container is sampled. According to this plan, samples are taken from n sampling units (containers/pack) selected at random.

Sampling plan for primary packaging material

[] In case of primary packaging material, select no. of reels/pack/ container for sampling as per “n plan”.

Collect approximately 1 feet sample of foil/film from each of selected reels of films/foils.

[] In case of bottle/cap/dropper/stopper, take randomly 10 samples from selected containers.
[] In case of Container/Jerry can/Cap for Jerry can; check physical appearance of at least 3 samples from each selected container/pack (selected as per “n plan”) and then take randomly two containers for laboratory test from selected container/pack.

Sampling plan for secondary packaging material

[] For secondary packaging material, select container/pack for sampling as per “n plan”.
[] Samples can be withdrawn from any part of the container (usually from the top layer).
[] Collect sample proportionally from the selected container/pack following ‘Sampling quantity for Packaging Material’ (as per Annexure-II).
[] In case of Shipper carton and Master carton, check physical appearance and text of at least 3 shipper cartons from each selected pack and then take randomly 3 shipper cartons for laboratory test from selected pack.
[] Inform Warehouse before going for sampling to arrange the packaging material containers.
[] Take ‘Sampled’ label, sampling tools, packaging material sampling report, sampling basket and GRN before sampling.
[] Check the physical condition and cleanliness of packaging material containers/packs before opening for sampling.
[] If any container/pack found in damaged condition, intimate warehouse in-charge.
[] Damaged containers/packs whose integrity is doubtful should be sampled and tested separately.
Inform warehouse in-charge to take initiatives for repacking of damaged container/pack if necessary.

 Sampling of packaging materials

[] Check the details given on the GRN with the manufacturers label and ensure that the “Quarantine” label affixed properly by the warehouse personnel on all packaging material containers/packs of a consignment.

[] Check the physical condition of outer pack/container/damage condition.
[] Microbiology personnel will collect sample first in sampling booth for microbial analysis (when applicable).
[] Check the physical condition such as appearance (in case of Shipper carton/Master carton, Container/Jerry can/Cap for Jerry can), winding (in case of foil/film) etc. of the packaging material for any gross abnormalities. Measure internal core diameter, total reel diameter (in case of foil/film) of three reels. [] Record all necessary information in ‘Packaging Materials Sampling Report’ (as per Annexure-IV).
[] Select number of containers/bags/packs and collect sample according to sampling plan. Repair the sampling point properly, close the container/pack and affix the ‘SAMPLED’ label in cascading manner (overlapping upto half of the status bar of the previous label) over the “QUARANTINE” label without hiding any information of the previous label. Affix ‘UNDER TEST’ label on all other containers of the consignment in the same way.

[] Enter the information about the material sampled i.e. date, GRN No., lab. control no., name of  material, code no., invoice no./challan no., manufacturer lot no., manufactured by, sampled quantity, sampled by and remarks (if any)  into the ‘Sampling Register for Packaging Material’ (as per
Annexure-III).
[] Record sampling details in ‘Packaging Materials Sampling Report’ (as per Annexure-IV).
[] If any discrepancy found, immediately inform the warehouse in-charge to take action accordingly.
[] Transfer the collected samples to QC laboratory.

Release:

[] On receipt of the packaging material sample from warehouse, QC will keep them into “Under test sample (packaging material)” labeled rack in sample receiving room or any other designated place with proper labeling.
[] Enter the sampled by (initial) in the ‘Packaging Material Log Register’ (as per Annexure-I).
[] In-charge/Sr. Executive, QC will issue the packaging material work sheet with initial and date on every page to the analyst and enter the worksheet issued by (initial and date) in the ‘Packaging Material Log Register’ (as per Annexure-I).
[] Carry out the physical appearance test very carefully.
[] Test all parameters according to the packaging material specification and the packaging material test method and record the analytical raw data and calculations, and attach the printout of weight(s) in the analyst logbook.
[] Fill up the respective Packaging material work sheet (as per Annexure-V) and attach printout of required raw data.
[] Accordingly prepare the ‘Certificate of Analysis for Packaging Material’ (as per Annexure-VI).
[] Use bracket like [  ] to indicate that the result is taken from manufacturer’s certificate of analysis (COA).
[] Keep a remarks on ‘Certificate’, if any minor observation (variation in dimension, colour etc.) is found for a batch of packaging material.
[] Compile a batch report with COA, test report (packaging material work sheet), packaging materials sampling report (prepared as per Annexure-IV), QC copy of GRN.
[] Keep one retention sample with the bunch if feasible.
[] If it is not possible to keep retention sample with the bunch, keep them into another box/pack with proper labeling.
[] Submit the batch report with respective packaging material specification to Executive/Sr. Executive, Quality Control for checking.
[] Check and verify the test result against Packaging Material Specification. Inform production department for machine trial or practical trial for a particular material, if required.
[] Executive, Production is responsible for machine trial and reporting.
[] On completion of checking/verification, enter the detail in the ERP.
[] Submit GRN, testing report and COA to In-charge/Sr. Executive, QC for checking and approval. Give part release to fulfill the production demand, if required.
[] In-charge, QC/Sr. Executive, QC will check report and approve finally for passed/rejected status of the packaging material.
[] Officer/Executive, QC will prepare status label (Passed/Rejected) after approval of GRN. The expiry and retest should be not applicable for all secondary packaging materials, glass bottle, ampoule, plastic container/cap/dropper/stopper/syringe, polyethylene bag, aluminium cap, sealing foil and alu-lid foil. In case of PVC, PVdC film and Alu-bottom foil; the expiry and/retest should be as per manufacturer’s recommendation. If not mentioned by manufacturer, then the expiry period for PVC, PVdC film and Alu-bottom foil should be five years.

[] Officer/Executive/Sr. Executive, QC will check and sign on the passed label.
[] Only the rejected label will be signed by In-charge/Sr. Executive, QC.
[] After release of consignment entry information regarding a passed/rejected GRN in “Packaging material log register” (as per Annexure-I).
[] After approval send copy of GRN to warehouse/Store.
[] QC Executive or QC sampler will affix status label (Passed/Rejected) in cascading manner (overlapping upto 3/4 th of the status bar of the previous label) over the “SAMPLED” or “UNDER TEST” label without hiding any information of the previous label.
[] Enclose mail or any other relevant document and approved GRN, with the respective batch document.
[] Keep a copy of GRN with batch document and file it up.

List of Annexes: Packaging Material Sampling and Release Procedure

[] Annexure-I     : Packaging Material Log Register
[] Annexure-II    : Sampling quantity for Packaging Material
[] Annexure-III   : Sampling Register for Packaging Material
[] Annexure-IV   : Packaging Materials Sampling Report
[] Annexure-V    : Packaging Material Work Sheet
[] Annexure-VI   : Certificate of Analysis for Packaging Material

Packaging Material Sampling and Release Procedure Read More »

Storage Conditions of Raw Materials and Packaging Materials

Storage Conditions of Raw Materials and Packaging Materials, Purpose:

The purpose of this procedure is to describe the instruction of storage conditions of raw materials and packaging materials.

Storage Conditions of Raw Materials and Packaging Materials, Scope:

This SOP is applicable for storage conditions of raw materials and packaging materials to Quarantine Area, Ambient Store, AC Store, Finished Goods Store, Capsule Shell Store and Central Warehouse of XX Pharmaceuticals Ltd.

Definitions/Abbreviation:

[] Ambient Store: Storage area with normal environment condition.
[] MSDS: Material Safety Data Sheet.

Responsibilities:

The roles and responsibility is as follows:

Executive, Warehouse

[] Maintain storage conditions of all raw and packaging materials as per Manufacturer’s instruction or according to specification.
[] Record the temperature and humidity of the material storage room.
[] Follow the instructions of this procedure correctly.

Executive, Quality Compliance

[] Verify the storage conditions of raw and packaging materials.

 General Manager, Plant

[] Ensure that all raw and packaging materials are stored properly.
[] Ensure appropriate personnel from the section are trained on this procedure and evaluate the effectiveness of training.
[] Confirm that SOP is technically sound and reflects the required working practices.

Head of Quality Assurance

[] Approval of SOP.
[] To ensure the overall implementation of the SOP.

Procedure:
Precaution(s):

[] Precautions must be taken to prevent unauthorized entry in the storage areas.
[] All stores must be secured with lock and key.

Storage Conditions:

Maintain Storage conditions as below:
[] Quarantine Area :Below 25°C
[] Ambient Store:Below 40°C
[] AC Store:Below 25°C

Finished Goods Store:Below 30°C

Capsule Shell Store:Temperature Below 25°C & Relative Humidity Below 60%
Central Warehouse:Below 25°C

 Storage of the materials:

[] Carry out the emergency plan if temperature goes above 25°C for AC store.
[] Record the temperature and humidity for the time when temperature goes above 25°C.
[] Inform QA department immediately providing all recorded data and existing product status.
[] Check the recorded data and evaluate the sensitive material, which might temperature sensitive.
[] Send the advice to Quality Control Department for retesting of that sensitive material before use in production.
[] Carry out tests as described in the respective test method.
[] Analyze the impurity of the substance, if required.
[] Affix “REJECTED” label on the existing label of the container when retesting result does not comply with specification.
[] Prepare a list for storage condition of raw materials and packaging materials as per Annexure-VII; then take approval from Head of Quality Assurance.

[] Update the list for storage condition of raw materials and packaging materials three months to yearly or when required.

Recording of storage conditions:

[] Sr. Executive/Executive, Quality Compliance will issue the ‘Temperature & Relative Humidity Record Sheet of Warehouse’ as per Annexure-I to Annexure-VI
[] Executive, Warehouse by maintaining proper record.
[] Record the temperature and humidity of Quarantine Area, Ambient Store, AC Store, Finished Goods Store, Capsule Shell Store and Central Warehouse thrice in a day in ‘Temperature & Relative Humidity Record Sheet of Warehouse’ prepared as per Annexure-I to Annexure-VI.
[] Maintain the storage condition as per QA approved Storage Condition of Raw materials and Packaging materials.

List of Annexes

1.0 Annexure-I: Temperature Record Sheet of Quarantine Area.
2.0 Annexure-II: Temperature Record Sheet of Ambient Store.
3.0 Annexure-III: Temperature Record Sheet of AC Store.
4.0 Annexure-IV: Temperature Record Sheet of Finished Goods Store.
5.0 Annexure-V: Temperature & Relative Humidity Record Sheet of Capsule Shell Store.
6.0 Annexure-VI: Temperature Record Sheet of Warehouse Central Warehouse.
7.0 Annexure-VII: Format of Storage Condition of Raw materials and Packaging materials.

 

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Retesting of Raw and Packaging Material Standard Operating Procedure

Purpose:

The purpose of this procedure is to describe the process for retesting of raw material and packaging materials (before retest date).

Scope:

This procedure is applicable for all raw materials (APIs and excipients) and some packaging materials received in XX Pharmaceuticals Limited.

Definitions/Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]QC: Quality Control.
[][]API: Active Pharmaceuticals Ingredients

Responsibilities:

The roles and responsibility is as follows:

Officer/Executive/Sr. Executive, QC & Microbiology

[][]To ensure that the instructions of this procedure are correctly followed.
[][]To maintain the records properly as per SOP.

Executive, Warehouse

[][]To send retest request to QC in time.
[][]To ensure availability of containers to be sampled from quarantine area to the sampling booth and their replacement after sampling.
[][]To ensure cleanliness of Sampling booth and containers to be sampled.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP reflects the required working practices.
[][]To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.

Head of Quality Assurance

[][]Approval of the SOP.
[][]To ensure the overall implementation of the SOP.

Procedure:

[][]Mention the retest date on passed label at the time of first release.
[][]Frequency of re-testing will be one year from test date.
[][]If the next retest date exceeds the expiry date, assign the retest date same as expiry date.
[][]The expiry date provided by the manufacturer will not be extended in any circumstances for active raw material.
[][]In case of excipients and packaging material, the expiry date may be extended on the basis of retest result if the expiry date is mentioned as best before/use before/retest date in manufacturer’s COA.
[][]In such cases, recommended expiry will be assigned instead of expiry and the next retest frequency will be every six months.
[][]The expiry date may be extended as per manufacturer’s recommendation.
[][]If there is no manufacturer’s recommendation, the expiry date may be extended twice for every six month up to one year from expiry date on the basis of retest result.
[][]Executive, warehouse will raise ‘Retesting Advice Form’ (as per Annexure-I) by ERP for the identified raw/packaging materials subject to retest or expiry.
[][]In case of material to be retested, warehouse will send the retest advice form at least 7 days before the retest date and QC will test and release/reject retested material within the retest date.
[][]In case of material to be expired, warehouse will send the retest advice form on the expiry date and QC will reject the expired material after necessary entries in retest advice form.
[][]QC will receive retesting advice form from warehouse and enter necessary information in Raw Material Register and assign the new Lab. Control No. for retest as below:
e.g. Lab. Control No./R1
Where, Lab. Control No. is of the identified material subject to retest.
/ is separator
R1 is retest for first time (e.g. R1, R2…..)
[][]Take sample from last used container for active and excipients sufficient for necessary retest parameters to relevant test specification.

[][]Collect sample following SOP for Raw material sampling and release procedure SOP for Packaging material sampling and release procedure and affix ‘UNDER RETEST’ label on the previous ‘PASSED’ label in cascading manner.

Carryout the following tests for each raw material

[][]Description/Appearance
[][]LOD/Water Content/Moisture Content
[][]Chromatographic Purity/Related Substance
[][]Assay
[][]pH/Acidity/Alkalinity test
[][]Microbial limit test
[][]Bacterial Endotoxin test
[][]Other relevant test (If necessary)
[][]Carry out required tests as described in the respective test method.
[][]Record analytical raw data in analytical worksheet and analyst logbook. Entry all results in certificate of analysis in ERP.
[][]Verify the test report against specification in ERP.
[][]Follow SOP for handling of out of specification if the test result does not comply with the specification.
[][]After approval/rejection, take print out the COA and two copies of approved ‘Retesting Advice Form’.
[][]Attach the retest report and related documents with the previous test reports.
[][]Prepare the required number of status labels (PASSED/REJECTED) for retested material.
[][]QC will send a copy of approved ‘Retesting Advice Form’ to warehouse.

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Manufacturing Trend Analysis Standard Operating Procedure

Manufacturing Trend Analysis, Purpose:

Manufacturing Trend Analysis, the purpose of this SOP is to define a procedure for trending of manufacturing data and to ensure that management reviews the trends and takes appropriate action.

Manufacturing Trend Analysis, Scope:

This procedure is applicable for all products manufactured at general block and are analyzed in Quality Control and Microbiology Laboratory of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]QC: Quality Control.

Responsibilities:

[][]The roles and responsibility is as follows:
[][]Executive/Executive, QC & Microbiology
[][]To ensure that the instructions of this procedure are correctly followed.
[][]To maintain the records properly as per SOP.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.
[][]To ensure effective assessment of trend analysis of Product.
[][]Take correction action to prevent reoccurrence.

Head of Quality Assurance

[][]Approval of the SOP.
[][]Review all trend analysis to take appropriate action.
[][]To ensure the overall implementation of the SOP.

Procedure:

[][]Manager, Quality control will issue the ‘Finished Product Trend Card’ (Annexure-I) by making entry in the ‘Trend Card Issue Register’ (Annexure-II)
[][]QC Executive will make entry in ‘Finished Product Trend Card’ and MS Excel format at the time of report submission.

Trend the following key parameters by QC Executive taken from IPC data:

Tablet:

[][]Disintegration Test
[][]Average weight

Capsule:

[][]Disintegration Test
[][]Filled weight

Powder for suspension:

[][]Filled weight
[][]Trend the following key parameters by QC Executive taken from analytical data:

Tablet:

[][]Assay (Active content)
[][]Dissolution Test (if applicable)

Capsule:

[][]Assay(Active content)
[][]Moisture content
[][]Dissolution Test (if applicable)

Powder for suspension:

[][]Assay (Active content)
[][]Moisture content
[][]Dissolution Test (if applicable)
[][]Quality Control Manager will review the trend at the time of report approval.
[][]If there are any atypical findings that indicate potential quality or performance issues, then follow the below instruction:
[][]Carry out an immediate laboratory investigation as per procedure for out of specifications. But this action will not prevent from releasing the batch to commercial.
[][]If the laboratory investigation indicates that there is no laboratory error, then it must be reported to AGM, Quality Assurance to conduct an investigation and take action to bring the situation in control.
[][]Preserve all the data securely for Periodic Product Review.

List of Annexure:

Annexure-I: Finished Product Trend Card
Annexure-II: Trend Card Issue Register

Manufacturing Trend Analysis Standard Operating Procedure Read More »

Raw Material Sampling and Release Standard Procedure

Raw Material Sampling and Release, Purpose:

Raw Material Sampling and Release, the purpose of this procedure is to describe the process for sampling and release of the raw materials (actives and excipients).

Raw Material Sampling and Release, Scope:

This procedure is applicable for all raw materials (APIs and Excipients) received in XX Pharmaceuticals Limited.

Definitions/Abbreviation:

[][]QC: Quality Control
[][]API: Active Pharmaceuticals Ingredients
[][]GRN: Goods Received Note
[][]CoA: Certificate of Analysis
[][]AQL: Acceptance Quality Limit
[][]BOPP: Bi-axially Oriented Polypropylene
[][]Mfg. Date: Manufacturing Date
[][]Exp. Date: Expiry Date
[][]ERP: Enterprise Resource Planning
[][]SS: Stainless Steel

Responsibilities:

The roles and responsibility is as follows:

Officer/Executive, QC and Officer/Executive, Microbiology

[][]To ensure that the instructions of this procedure are correctly followed.
[][]To maintain the records properly as per SOP

Executive, Warehouse

[][]To ensure availability of containers to be sampled from quarantine area to the sampling booth and their
replacement after sampling.
[][]To ensure cleanliness of sampling booth and containers to be sampled.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP reflects the required working practices.
[][]To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.

Head of Quality Assurance

[][]Approval of the SOP.

Procedure:
General Precaution(s):

[][]Take sample for microbial testing first followed by other sampling.
[][]Use clean and dry sampling device for sampling.
[][]Use sampling device after moping with freshly prepared 70% IPA for collecting the sample for microbiological limit test.
[][]Material of only one consignment shall be sampled at a time.
[][]Use different sampling devices for sampling of different materials.
[][]For sampling of volatile and hazardous chemicals and solvents, follow instructions as given in their handling procedures.
[][]All solid as well as liquid raw materials except solvents are to be sampled in sampling booth.

Sampling: Raw Material Sampling and Release

[][]Receive the GRN for raw material from the warehouse then compare with Manufacture’s CoA and enter the details (GRN Received Date, GRN No., Lab. Control No., Name of material, Code No., Invoice/Challan No., Manufacturer Lot No., Manufactured by, Supplied by, Mfg. Date, Exp. Date, Qty. received, Received by & date) in the Raw Material Register (as per Annexure-I) maintained in QC department.
[][]If the Manufacture’s CoA is not received, inform to Supply Chain Department.
[][]Ensure that material is received from Approved Vendor.
[][]If the material is not from Approved Vendor, then the material is not to be sampled.
[][]Assign the work of sampling of the material to the QC Executive.
[][]Share the copy of GRN and Manufacturer CoA with Microbiology Laboratory, when required.
[][]Inform Warehouse to ensure cleanliness of sampling area and fill-up the Cleaning Checklist before Sampling of Raw Materials (Annexure-VIII) and then start-up of sampling booth.
[][]Assigned QC Executive will take required no. of “SAMPLED” label as per labeling SOP.
[][]Assigned QC Executive will prepare and checked ‘SAMPLING IN PROGRESS’ label (as per Annexure-II); prepare required containers/poly bags for sampling according to sampling plan for the material to be sampled.

Sampling plan

[][]In case of all active raw materials, carry out sampling from all containers in each of supplied batch for performing identification test individually for all the containers.
[][]In case of all excipient, carry out sampling from different containers in each of supplied batch according to formula √n + 1 e.g. for 10 containers sample from √10 + 1 = 4.16 ≈ 5 containers.

Sampling container

[][]Select the sample container according to the nature of the material to be sampled.
[][]Use clean fresh poly bags for solid materials.
[][]Use clean dry glass bottle with screw cap for liquid, dry amber glass bottle with screw cap for light sensitive liquid and transparent stoppered flask for solvents.
[][]Use sterilized screw capped conical flask (autoclaved at 121°C for 15 minutes) for sampling of raw material for microbial test.
[][]Sample all light sensitive solid materials in black polyethylene bag.
[][]Sample all the moisture sensitive materials in air tight container.

Sampling note: Raw Material Sampling and Release

Solid

If the material is in paper bag, take the sample by cutting a small ‘V’ on the bag and in case of Drum open the lid & inner polyethylene then push the Sampling thieve and take sample into a labeled poly-bag. Then place a clean poly-bag over the tear area and properly seal the poly-bag with adhesive tape. In case of Drum, tie the inner-polyethylene with rubber band/cable tie, finally twist the lid properly.

Liquid

Deep the liquid sampling device vertically into the sample drum and collect the sample or pipette after gently stirring the liquid and transfer the liquid sample to a labeled, cleaned container. Solvent in distorted metal drum must be sampled in addition to the rule of Ön + 1. Sample all flammable solvents in solvent dispensing room.

Sampling device

Use stainless steel sampling devices specially designed for solid and liquid material.

[][]For solid materials received in drums/container use specially designed S.S. sampling device by which material can be sampled from different level (thief sampler).
[][]For liquid and solvents received in drum, use specially designed S.S. drum sampler.
[][]For liquid material received in small container use specially designed small SS liquid sampler.
[][]For solid material received in bags use specially designed SS solid sampler/SS spoon.
[][]For microbiology analysis, use screw capped conical flask/glass bottle and SS spoon (autoclaved at 121°C for 15 minutes).
[][]Clean and maintain the sampling device (tools) as per SOP for cleaning and storage of sampling tools after completion of sampling.

Damaged containers or torn bags

[][]Check the physical condition and cleanliness of raw material containers before opening for sampling.
[][]If any container found in damaged condition, intimate warehouse in-charge.
[][]Damaged containers whose integrity is doubtful should be sampled and tested separately.
[][]Inform warehouse in-charge to take initiatives for repacking of damaged container or torn bags if necessary.

Gowning  procedure

[][]Wear fresh gown before entering into sampling booth.
[][]Wear sterile gloves, mask before sampling for microbiology analysis.
[][]Cover the hands with gloves and wear a cap and mask to cover hair and nose respectively.
[][]Cover the footwear with shoe cover.
[][]Use separate apron, nose mask, hand gloves, cap & shoe covers for sampling of different material.
[][]Mop the hands with 70% IPA and air dry before proceeding for sampling and particularly when samples are to be drawn for Microbiological testing.

Sampling procedure

[][]Check the Cleaning Checklist before Sampling of Raw Material (as per Annexure-VIII).
[][]Inform Warehouse before going for sampling to arrange the raw material containers which are to be sampled in sampling booth area and ensure the cleanliness of these containers externally, before bringing the container to be sampled to the sampling area.
[][]Enter the Warehouse (Raw Material) with sampling basket, sampling utensils, sampled label, poly-bags, GRN and ‘Sampling in progress’ label.
[][]Check the details given on the GRN with the suppliers label and ensure that the “Quarantine” label affixed by the warehouse personnel on all raw material containers of a consignment.
[][]Select number of containers/ bags as per sampling plan and inform Warehouse personnel to send the raw material containers to the material entry airlock.
[][]Check that ‘CLEANED’ label is affixed to the sampling booth and then affix the ‘Sampling in-progress’ label outside of the sampling booth. Enter the sampling booth.

Operate the sampling booth

[][]Receive the desired container(s) within material entry airlock. Check that the containers are free from dirt & dust externally. Do not sample the container/bag whose packing integrity has been lost (material has been exposed to environment).
[][]Take the raw material inside the sampling booth. Sample in a manner so that laminar airflow can be in operation without any interruption.
[][]Enter the information about the material sampled into the ‘Sampling Register’ i.e. Date, GRN No., Lab. Control No., Name of material, Code No., Manufacturer Lot no., Manufactured by,  Sampling start time (as per Annexure-IV).
[][]Wear disposable hand gloves just before start of sampling.
[][]Open the container for sampling one by one.
[][]Check the physical condition of the raw material for any gross abnormalities like dis-colourisation, lumps, foreign matter and physical heterogeneity. Record information in Raw Materials Sampling Report (as per Annexure-V).
[][]Collect the sample aseptically into sterile screw capped conical flask by sterilized sampling device for microbiology analysis.
[][]Assign the sampled Container No. as 1/25, 2/25, 13/25, 25/25 etc. with Reference to drum number of container sampled.
[][]Draw the sample from different levels of the container. (i.e. From Top, Middle & Bottom). The weight of the total sampled quantity should be according to List of Raw Material Sampling Quantity (prepared as per Annexure-III).
[][]For excipient, prepare composite sample by taking equal quantity of material from the sampled drum. Mix thoroughly in big polythene bag for retained sample and testing sample. For identification test take individual small quantity of sample from each sampled container.
[][]For active raw material, prepare composite sample during sampling for assay for every 10 containers of the consignment by taking equal quantity of material from individual sampled container. Mix thoroughly in plastic bag to make sample for assay test. For complete analysis (except identification and assay) and retention sample make composite sample by taking equal quantity from all bags or container during sampling. For identification test take individual small quantity of sample from each container.
[][]Take the individual sample from each sampled container for microbiological analysis in sterile container, if specified.

Reseal the container properly after sampling as follows: Raw Material Sampling and Release

[][]Fibre/Plastic container pack: Shrink the inside poly bag by twisting it sufficiently. Bent it & tie it using cable tie. Place the lid of container & close it tightly & seal it.
[][]Woven and Paper Bag: Close the sampling point and seal it properly using BOPP tape.
[][]Liquid RM container: Place the lid of container & keep it tightly closed.
[][]Affix yellow colour duly filled & signed ‘SAMPLED’ label on each containers from which the samples are collected and ‘UNDER TEST’ label on all containers of a consignment.
[][]After completion of sampling switch off the sampling booth.
[][]Record sampling details in Raw Materials Sampling Report (as per Annexure-V).
[][]Enter the Sampling end time, Sampled quantity, Sampled by and Remarks (if any) into the ‘Raw Material Sampling Register’ (as per Annexure-IV).
[][]Place the used sampling device in container labeled as ‘TO BE CLEANED’ containing a poly bag.
[][]Shift sampled container outside the sampling booth.
[][]Inform warehouse personnel to transfer it to quarantine area.
[][]Leave sampling booth and affix ‘TO BE CLEANED’ label outside the sampling booth. Inform warehouse personnel for cleaning.
[][]Warehouse personnel will clean the sampling booth, enter the sampling booth cleaned by in ‘Raw Material Sampling Register’ (as per Annexure-IV) and then affix ‘CLEANED’ label outside the sampling booth.
[][]If any discrepancy found, immediately inform the warehouse in-charge.
[][]Keep the collected samples in the sample receiving room of QC Laboratory in dedicated rack for Raw Material or in refrigerator, if specified.
[][]Keep the retention sample in retention sample room or in refrigerator, if specified.
[][]Enter the sampled by (initial) and date in the ‘Raw Material Log Register’ (as per Annexure-I).

Release:

[][]Enter the sampled by (initial) and date in the ‘Raw Material Log Register’ (as per Annexure-I).
Issue the Raw Material Analytical Work Sheet (as per Annexure-VI) (for commercial raw material) with initial and date on every sheet to the analyst and enter the worksheet issued by (initial and date) in the ‘Raw Material Log Register’ (as per Annexure-I).
[][]Carry out the physical appearance and identification test separately for active raw material from each container.
[][]Microbiology will perform microbial limit test from all sampled container and bacterial endotoxins test from composite sample.
[][]Perform identification test of excipient from all sampled containers.
[][]For active raw materials, prepare sub-composite sample from each 10 container and then prepare composite sample from all the sub-composite samples. Perform the test of sub-composite sample if composite sample shows out of specification result to identify easily which container(s) is in problem. Retain all the sub-composite samples until release of the material.
[][]For active raw materials perform rest of the test as per the specification from the composite sample prepared from all containers. Carry out assay test from the composite sample and take result.
[][]For excipient perform the complete test as per specification from the composite sample prepared from the sampled containers.
[][]Check the appearance of capsule shell according to Sampling Plan for Normal Inspection of Capsule Shell (as per Annexure-IX).
[][]Test all parameters according to the Raw Material Specification and analyze the batch exactly as written in the method of analysis.
[][]Record all analytical raw data and calculations, and attach the printout of weight(s) in the analyst logbook.
[][]Fill up the Raw Material Analytical Work Sheet (as per Annexure-VI) and attach printout of required raw data.
[][]Weigh the sample ± 5.0% of specified quantity for assay test and ±10.0% of specified quantity for all other tests.
[][]Use bracket like [ ] to indicate that the result is taken from manufacturer’s/supplier’s certificate of analysis (CoA) (if available).
[][]Entry all data in previously created certificate of analysis for raw materials in ERP (as per Annexure-VII).
[][]Verify the test report with specification followed by Approval/Rejection in ERP.
[][]Follow SOP for handling of out of specification if the test result does not comply with the specification.
[][]After approval/rejection print out the COA and two copies of GRN under the heading of

  • Approved/Rejected quantity.
  • Date of Release/Rejected.
  • Approved/Rejected status.

[][]Submit all report to QC Manager for approval.
[][]Submit one copy of GRN with the initial with date of In-Charge, QC or his/her designee to store.
[][]Compile a bunch with CoA (as per Annexure-VII), filled Raw Material Analytical Work Sheet (as per Annexure-VI) and raw data, Raw Materials Sampling Report (as per Annexure-V), QC copy of GRN after approval.
[][]Fill up the Trend Card with necessary data.
[][]Prepare the required number of green “PASSED” label for passed.
[][]In case of Rejection, prepare the required no. of red “REJECTED” label.
[][]Fill up the Raw Material Rejection Form (as per Annexure-X) for rejection of raw material.
[][]Paste “PASSED”/“REJECTED” label in cascading manner (overlapping upto 3/4 th of the status bar of the previous label) over the “UNDER TEST” label without hiding any information of the previous label.

List of Annexes: Raw Material Sampling and Release

Raw Material Sampling and Release Standard Procedure Read More »

Sampling Tools Cleaning and Storage SOP

Sampling Tools Cleaning and Storage; Purpose:

Sampling Tools Cleaning and Storage; The purpose of this procedure is to describe the instruction of cleaning and storage of sampling tools.

Sampling Tools Scope:

This SOP is applicable to sampling tools used for Quality Control Laboratory and Microbiology Laboratory at XX Pharmaceuticals Ltd.

Definitions/Abbreviation:

[][]SOP: Standard Operating Procedure: A written authorized procedure, which gives instructions for performing operations.
[][]QC: Quality Control.

Responsibilities:

[][]The roles and responsibility is as follows:
[][]Laboratory Attendant, QC & Microbiology
[][]To prepare of cleaning solution.
[][]To clean and store all sampling tools by following SOP.
[][]Executive, QC & Microbiology
[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]Arrange training on the SOP to all concerned personnel.
[][]To ensure implementation of the SOP after training.
[][]Schedule calibration of the instrument at the defined intervals.

Head of Quality Assurance

[][]Approval of the SOP.
[][]To ensure overall implementation of this SOP.

Procedure:

Precaution(s):
[][]Wear hand gloves, mask and protective clothing before cleaning of sampling tools.
[][]Be sure that the sampling tools are cleaned just after use.
[][]After cleaning of tools, be sure that the tools are free from any residual content of detergent or sample.
[][]During handling, sterilized gloves should be worn after sterilization of microbiology sampling tools.
Cleaning of Sampling Tools:

For scoop/spoon:

[][]Clean the sampling devices with potable water following by 0.5% soap or detergent solution.
[][]Finally rinse with purified water to remove the adhering material.
[][]Check the cleanliness physically and clean again if necessary.
[][]Dry in hot air oven for use in QC sampling.
[][]Sterilize at 2000C for 1 hour or autoclave at 1210C for 15 minutes for the sampling of Microbiology analysis.

For pipette (glass) and Glass Rods:

[][]Pass the running potable water through the pipette to remove the adhering material.
[][]Sink the pipette into 0.5% soap or detergent solution.
[][]Rinse with potable water to remove detergent.
[][]Finally rinse with purified water.
[][]Confirm that the tools are cleaned properly, clean again if it is necessary.
[][]Dry in hot air oven for use in QC sampling.
[][]Sterilize at 2000C for 1 hour or autoclave at 1210C for 15 minutes for the sampling of Microbiology.

Storage of Sampling Tools:

[][]After dry, remove the cleaned tools from the oven and wrap the dry tools individually with cleaned polybag.
[][]Ensure that there is no exposure of sampling tools after wrapping the cleaned dried tools with polybag.
[][]Finally keep it at closed condition.
[][]Affix the tag “CLEANED” label duly signed with date on the sampling tools.
[][]Use the tools within 7 days sampling of Chemical test and within 24 hours for sampling of microbiology test.

Sampling Tools Cleaning and Storage SOP Read More »

Sampling Booth Start-up, Operation and Cleaning

Sampling booth Purpose:

The purpose of this SOP is to describe the operation and cleaning procedure of Sampling Booth in order to comply with cGMP standard.

Sampling booth Scope :
The scope of the procedure is applicable to the Sampling Booth installed at the Warehouse of general block of XX Pharmaceuticals Limited.

Definitions/Abbreviation:

[][]SOP: Standard Operating Procedure
[][]QC: Quality Control

Responsibilities:

The Roles and Responsibilities are as follows:

Officer/Executive/Sr. Executive, Quality Control

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Executive, Warehouse

[][]To ensure that this procedure is followed.
[][]To check & ensure cleaning of sampling booth.

Manager, Quality Control

[][]To confirm that the SOP is technically sound and reflect the required working practice.
[][]To arrange the training on the SOP to all concerned personnel and to ensure the implementation of the SOP after training.

Head of Quality Assurance

[][]To approve the Document
[][]To ensure the overall implementation of the SOP.

Procedure

Precautions:
[][]The working person must follow safety procedures of works.
[][]For any trouble, disturbance switch OFF the Sampling Booth.
[][]Don’t sampling solvent and flammable liquid inside the sampling booth

Operation

[][]Check the Sampling Booth first physically.
[][]Check electric connection and mechanical set up.
[][]Machine switch on.
[][]Light on and blower on.
[][]Open the door.
[][]After completion desired work clean the Laminar Unit properly.
[][]Close the door and switch off main switch.
[][]Switch ON Sampling Booth.
[][]Switch ON Light.
[][]Switch ON the Laminar Air Flow.
[][]Increase or decrease air flow by pressing up/down button.
[][]Operate the Sampling Booth for 30 minutes before starting sampling.
[][]Record the machine operation start time & end time and other parameters on the  Equipment Log Book’

Cleaning

[][]Remove dust from the Sampling Booth with a vacuum cleaner and then clean with lint free cloth.
[][]Clean the booth with wet mop.
[][]Wipe the water with lint free cloth.
[][]After final cleaning affix the ‘CLEANED’ label.
[][]Record the cleaning status in the ‘Equipment Log Book’.

Download Here:

[][]Annexure I: Equipment Log Book

Sampling Booth Start-up, Operation and Cleaning Read More »

Instrument calibration Standard operating procedure

Instrument calibration Purpose:

Instrument calibration, This SOP ensures that all type laboratory instruments of QC, PD, IPQC, Microbiology and balances of Production department are appropriately calibrated and calibration status maintained on due time.

Scope :

This procedure is applicable for calibration frequency of all types of laboratory instruments installed in QC, PD, IPQC, Microbiology and balances of Production department of General Block of XX Pharmaceuticals Ltd.

Definitions :

[][]QC: Quality Control.
[][]ENG: Engineering department.
[][]PD: Product development.
[][]IPQC: In-process Quality Control.

Responsibilities:

The roles and responsibility is as follows:

Officer/ Executive

[][]Ensure that the instructions of this procedure are correctly followed.
[][]Ensure that all equipment’s are included in the Instrument list.
[][]Maintain and track the calibration schedule.
[][]Ensure that all equipment’s bear appropriate calibration label and are used after calibration.
[][]To verify the third party calibration report and raw data.

Manager, Quality Control

[][]Ensure that this procedure is kept up to date.
[][]Ensure that the calibration requirement are assessed and are fully documented for all pieces of the instrument.
[][]Ensure appropriate personnel from the section are trained on this procedure.
[][]Confirm that SOP is technically sound and reflects the required working practices.

Manager, Quality Assurance

[][]Approval of SOP.
[][]Approval of calibration frequency and calibration schedule.

Precaution(s):

[][]There are no significant hazards or special instructions relating to the process/activities described in this SOP.

Procedure:

[][]Calibrate the equipment regularly as per frequency stated in the instrument calibration frequency (prepared as per format in Annexure-I) and as per calibration due date stated in the instrument calibration schedule (prepared as per format in Annexure-II) for individual equipment.
[][]Review the instrument calibration frequency when new instrument is included.
[][]Review the instrument calibration schedule yearly.
[][]Mention the responsibility (Third Party / Supplier name) for external calibration and (calibrator name and department) for internal calibration.
[][]Calibrate the instrument within 3 days of calibration due for monthly calibration period, within 7 days of calibration due for 3 and 6 monthly calibration period and 15 days of calibration due for yearly calibration period.
[][]In case of any breakdown or replacement of any damaged part where calibration needs to be carried out, the calibration schedule will be reviewed accordingly.
[][]Executive/ Sr. Executive of respective department will intimate the Engineering department/ Supplier service engineer/ outside agencies for the calibration of the instruments/ equipments.
[][]Maintain all standards, reagents, instruments and equipments etc. required for calibration.
[][]Calibrate the instrument across the operating range at a frequency appropriate to the reliability and frequency of use. Tolerance must be specified and should reflect the manufacturer’s specification or process tolerance or whichever the tightest.
[][]Re-evaluate calibration requirement immediately if there is any change in the instrument in use.
[][]Calibration must be performed by trained personnel or by approved Third Party Service Engineer.
[][]Calibration record must include:
=>Equipment name, model number and instrument ID No.
=>The name of the person who carried out the calibration.
=>Date of calibration.
=>The date when calibration is next due.
[][]For calibration, use reference standards or reference instruments whose calibration is traceable.
[][]Store the calibration device, certified standard weight in a secure place.
[][]For internal calibration, affix the calibration sticker label “ CALIBRATED” (format of calibration labels should be as per SOP: Calibration management program, Ref. No. SOP/ENG/00Y/XX, where XX refers to current version no.), with performer initial, date of completion and calibration due.
[][]For external calibration, affix the calibration sticker provided by external calibrator with performer’s initial, date of completion and calibration due.
[][]If the instrument is found out of tolerance/ limit during calibration, a label ‘Out of calibration” will be affixed on the instrument (as per SOP: Calibration management program No. SOP/ENG/00Y/XX, where XX refers to current version no.).

Notify the relevant person/ department/ organization to repair (or replace if necessary) the instrument in a timely manner.

 

Download

Annexure I Instrument Calibration Frequency
Annexure II Instrument Calibration Schedule

Instrument calibration Standard operating procedure Read More »

Assigning of laboratory control number for different items

Assigning of laboratory control number; Purpose

The tenacity of this SOP is to define the procedure of assigning Laboratory control number (Lab. Control No.) of all type raw material, packaging material, water, intermediate, bulk and finished product that are analyzed in Quality Control and Microbiology Laboratory.

Assigning of laboratory control number; Scope

This procedure is applicable for all type of raw materials, packaging materials, water, intermediate, bulk and finished products of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[] GRN: Goods Received Note

[] Lab. Control No.: A system of alpha-numerical number which represents request for analysis of materials/ water/ products received from respective department.

[] QC: Quality Control.

[] SAF: Sampling Advice Form

Responsibilities

The roles and responsibility is as follows:

[] Sr. Executive/Executive, Quality Control & Microbiology

[] To confirm that this procedure is followed.

[] To maintain the records properly as per SOP.

Assistant Manager, Quality Control

[] To confirm that this procedure is kept up to date.

[] To check that the SOP reflects the required working practices.

[] Organize training on the SOP to all concerned personnel.

[] To confirm implementation of the SOP after training.

Head of Quality Assurance

[] To ensure the overall implementation of the SOP.

[] Take initiative to Approval of the SOP.

Procedure:

[] All newly delivered samples & the accompanying documents (e.g. test request) must be assigned a separate registration number.

[] Assign Laboratory control number (Lab. Control No.) in following way:

Put first two or three letters according to the abbreviations mentioned below –

  • BBW     Boiler Blowdown Water
  • BFW     Boiler Feed Water
  • CTW     Cooling Tower Water
  • DW       Drinking Water
  • EM       Environment Monitoring
  • ET        Endotoxin Test
  • ETP      Effluent Treatment Water
  • FP        Bulk Product (Semi-Finished)
  • GMB     General Microbiology
  • PM       Packaging Material
  • PMS     Packaging Material of Source Approval
  • PSC     Purified Steam Condensate
  • PTW     Potable Water
  • PW       Purified Water
  • RM       Raw Material
  • RMS     Raw Material of Source Approval
  • SHC     Sodium Hypochlorite
  • ST        Sterility Test
  • STB      Stability Sample
  • WFI      Water for Injection
  • WW      Wash Water

Write down a hyphen (-) after the abbreviation, then serial number consist of three digits i.e. 001, then a  slash and put two digits of month i.e. 08 for month August.

Again write down a slash (/) then last two digits of the year i.e. XX for year 20XX. For example, first raw material received on August 20XX will get the Lab. Control No.: RM-001/08/XX.

GMB will be included before abbreviation of each test in case of microbiology lab control no./lab reference no. and put slash (/) after that.

Record Lab. Control No. in Register against each GRN / SAF.

Record the same in respective documents and status label also.

Assigning of laboratory control number for different items Read More »

Specification and analytical method preparation and review

Specification and analytical method; Purpose

The tenacity of this SOP is to define the procedure for preparation, review & approval of specification & analytical methods in quality control & microbiology laboratory.

Scope

This procedure is applicable for all raw materials (APIs and excipients), water, packaging materials and finished products of  XX Pharmaceuticals Limited.

Definitions/Abbreviation:

[] COA: Certificate of Analysis

[] ERP: Enterprise resource planning

[] PMS: Packaging material specification

[] QA: Quality Assurance

[] QC: Quality Control

Responsibilities

The roles and responsibility is as follows

Officer/Executive/ Senior Executive, Quality Control

[] To confirm that this procedure is followed.

[] To retain the records properly as per SOP.

Assistant Manager, Quality Control

[] To confirm that this procedure is kept up to date.

[] To ensure that the SOP is technically sound & reflects required working practices.

[] Arrange training on the SOP to all concerned personnel.

[] To confirm implementation of the SOP after training.

Head of Quality Assurance

[] Take initiative to approval of SOP.

[] To ensure overall implementation of this SOP.

Procedure

Precaution(s)

There is no significant precaution or special instructions relating to the activities described in this SOP.

Preparation
  • Enter code no. in ERP, then assign the specification reference number using the format and the analytical method reference number using the specific format
  • Check whether, material is included in different Pharmacopeia [BP/EP/USP] or not.
  • Prepare specification & analytical method strictly align with Pharmacopeia if the material is included in BP/EP/USP.
  • Prepare specification & analytical method strictly align with Manufacturer’s guides/COA /analytical methods if the respective raw material or packaging material is not encompassed in BP/EP/USP. Include any additional test parameter as internal requirement.
  • QC will share rest of the QC test sample & raw data with PD. PD will suggest to include any in-house parameter in specification (as when required/not).
  • Compare specification & analytical method received from two or more suppliers; prepare specification & analytical method based on the suitable one based on feasibility study on site. Discuss with the concerned suppliers in case any difference identified.
  • For printed packaging material, Officer/Executive, QC will receive copy of artwork & approved shade card/design from QA and then prepare the specification and transfer to QA for approval. After approval of the specification, QC will receive control copy of specification along with artwork and approved copy of shade card/design from QA.
  • QC will prepare specification for unprinted packaging materials (Foil, Sachet, PVC/ PVDC Film etc.).
  • The issue date & review date should be in the day-month-year (dd-month-yyyy) format i.e. 25-August-20YY.
  • Assign two years review time for next revision from date of preparation for specifications and analytical methods.
  • For draft specification & analytical method; assign one year review time from date of preparation.
  • Follow respective standard format (as per concerned Annexure) for the preparation of specification & analytical method.
  • Enter final specification of raw material & packaging material in the ERP.
Review
  • Review specification & analytical method from draft to final one & change version no. to next one.
  • Review final specification & analytical method with a proper change control procedure when any change   is necessary.
  • Review method & specification if there is any change in respective Pharmacopeia. Put a new version number with a new review date.
  • If no modification is required at the time of review, then use subsequent review portion assign next expiry date 2 years from the review date and use the same.
Approval
  • Check analytical method & specification.
  • Manager, QA or Manager, QC will give approval after ensuring that each page of the document has been signed by person who prepared & person who checked specification after its finalization.
  • Keep master document in QA department.
  • Keep controlled copy in the QC & Microbiology department (as when required).
  • Retrieve previous specification & analytical method by revised one after review. Treat previous one as ‘OBSOLETE’.
  • Keep the ‘OBSOLETE’ copy in a file after stamping as ‘OBSOLETE’ in red ink
  • Discard the ‘OBSOLETE’ specification least after two years from the date of obsolete.

 

Download All Annexure here

Annexure I Format for Packaging Material Specification

Annexure II Format for Raw Material or Water Specification

Annexure III Format for Finished Product Specification

Annexure IV Format for Analytical Method of Raw Material or Water

Annexure V Format for Analytical Method of Packaging Material

Annexure VI Format for Analytical Method of Finished Product

 

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HPLC analysis and system suitability check procedure

HPLC analysis and system suitability; Purpose:

The purpose of this SOP is to describe the procedure for HPLC analysis and checking of system suitability.

HPLC analysis and system suitability; Scope

This procedure is applicable to all HPLC analysis that will be carried out in quality control laboratory of XX Pharmaceuticals Limited.

Definitions/Abbreviation
  • Standard Operating Procedure (SOP)
  • Standard Operating Procedure. A written authorized procedure, which gives instructions for performing operations.
  • HPLC: High performance liquid chromatography
  • QC: Quality Control
  • RSD: Relative standard deviation
Responsibilities

The roles and responsibility is as follows:

Officer/Executive/ Senior Executive, Quality Control

  • To ensure that the instructions of this procedure are correctly followed.
  • To maintain the records properly as per SOP
Assistant Manager, Quality Control
  • To confirm that this procedure is kept up to date.
  • To check that the SOP reflects the required working practices.
  • To organize training on the SOP to all concerned personnel & to ensure implementation of the SOP after training.
Head of Quality Assurance
  • Take initiative to approval of the SOP.
  • To confirm the overall implementation of the SOP.

Procedure:

General Precaution(s):

  • Ensure that the mobile phase is filtered and degassed properly by sonication before use.
  • Suggested injection procedure should be run in one single sequence.
Analytical procedure:
  • Prepare desired mobile phase, filtered by 0.22 or 0.45 µm membrane filter & degassed for at least 5 minutes with the help of sonication.
  • Equilibrate the column for at least 30 minutes or more until baseline gets stabilized with desired mobile phase & check the baseline to ensure the system is ready for injection.
  • Prepare standard solution & assay sample and keep record of weights.
  • At first inject blank to confirm the absence of unknown peak at the retention time of Principal peak & then inject standard solution to check retention time of the principal peak of interest. Run chromatogram minimum 2 minutes extra after principal peak elution is over and peak is properly integrated.
  • Unless otherwise specified in the individual method, data from five replicate injections of standard are used to calculate RSD, if the requirement is 2.0% or less; data from six replicate injections are used if the RSD requirement is more than 2.0%. Tailing factor of principal peak of interest should be between 0.8 and 1.5 unless otherwise stated in individual method.
  • Inject standard & assay preparation solution into the HPLC system as per suggested injection procedure previously mentioned.
  • Following are the suggested injection procedure to be followed unless otherwise specified in respective method.
Injection procedure for test homogeneity of Blend/Granules sample
Sample ID with No. of Injection
  • Blank: 1 Time
  • Resolution or System Suitability solution (If applicable) : 1 Time
  • Standard: 5 Times
  • Sample-1: 1 Time
  • Sample-2: 1 Time
  • Sample-3: 1 Time
  • Sample-4: 1 Time
  • Sample-5: 1 Time
  • Sample-6: 1 Time
  • End Standard: 1 Time
Injection procedure for Assay
  • Blank: 1 Time
  • Resolution or System Suitability solution (If applicable) : 1 Time
  • Standard: 5 Times
  • Sample: 1 Time
  • End Standard: 1 Time
Injection procedure for dissolution
  • Blank: 1 Time
  • Resolution or System Suitability solution (If applicable) : 1 Time
  • Standard: 5 Times
  • Sample-1: 1 Time
  • Sample-2: 1 Time
  • Sample-3: 1 Time
  • Sample-4: 1 Time
  • Sample-5: 1 Time
  • Sample-6: 1 Time
  • End Standard: 1 Time
Injection procedure for Content Uniformity
  • Blank: 1 Time
  • Resolution or System Suitability solution (If applicable) : 1 Time
  • Standard: 5 Times
  • Sample-1: 1 Time
  • Sample-2: 1 Time
  • Sample-3: 1 Time
  • Sample-4: 1 Time
  • Sample-5: 1 Time
  • Sample-6: 1 Time
  • Sample-7: 1 Time
  • Sample-8: 1 Time
  • Sample-9: 1 Time
  • Sample-10: 1 Time
  • End Standard: 1 Time
  • For injection of more than 12 samples, run end standard after every 12th sample.
  • Calculate the result comparing the area of sample solution with the average area of 5th standard (6th standard if six replicate injections required) and respective end standard.
Chromatogram review and documentation:

The custom report covers the following information and can be modified as per the specific need.

  • Acquired by
  • Sample Name
  • Sample ID
  • Tray No.
  • Vial No.
  • Injection Volume
  • Data File
  • Method File
  • Batch File
  • Date Acquired
The peak table in custom report for standard covers the following data, however select other data as per requirement.
  • Title
  • Sample Name
  • Sample ID
  • Ret. Time
  • Area
  • Theoretical Plate
  • Tailing Factor
  • Resolution

The peak table in custom report for sample covers the following data, however select other data as per requirement.

  • Title
  • Sample Name
  • Sample ID
  • Ret. Time
  • Area
  • Result
  • Unit
General guideline:
  • In the test for Assay, run all Standard & Sample chromatograms minimum 2 minutes extra after the principal peak elution is over & peak is properly integrated or as per the method.
  • In Chromatographic Purity/Degradation/Related Substances, run the chromatogram 2.5 times the retention time of principal peak or as specified in individual method. In case of specific impurity analysis, run the chromatogram minimum 2 minutes extra after the principal peak elution is over and peak is properly integrated.
Allowable modification in chromatographic system:

Following are general criteria, which provide extent of allowable variation to get system suitability. The adjustments are allowed only to improve quality of chromatography unless otherwise directed in the respective method/pharmacopoeial monograph.

pH of mobile phase:

pH of aqueous buffer used in mobile phase preparation can be adjusted to within ± 0.2 units of the value or range specified. (Example: If specified pH is 7.0 then allowable limit for adjustment is 6.80 – 7.20)

Concentration of salts in buffer:

Concentration of salts used in the preparation of aqueous buffer employed in mobile phase can be adjusted within ± 10% if the permitted pH variation is met. (Example: If specified concentration is 1.0% then allowable limit for adjustment is 0.90%–1.10%)

Ratio of components in the mobile phase

Following adjustment limits apply to minor components of the mobile phase (specified at 50% or less). The amount(s) of these component(s) can be adjusted + 30% relative. However the change in any component cannot exceed + 10% of absolute (i.e. in relation to the total mobile phase). Adjustment can be made to one minor component in ternary mixture. Examples of adjustments for binary and ternary mixture are given below.

Binary mixtures

Specified ratio of 50:50: 30% of 50 is 15% absolute, but this exceeds the maximum permitted change of + 10% absolute in either component. Therefore, the mobile phase ratio may be adjusted only within the range of 40:60 to 60:40.

Specified ratio of 2:98: 30%of 2 is 0.6% absolute. Therefore the maximum allowed adjustment is within the range of 1.4:98.6 to 2.6:97.4.

Ternary Mixtures

Specified ratio of 60:35:5: For the second component, 30% of 35 is 10.5% absolute, which exceeds the maximum permitted change of + 10% absolute in any component. Therefore the second component may be adjusted only within the range of 25% to 45% absolute. For the third component, 30% of 5 is 1.5% absolute. In all cases, a sufficient quantity of the first component is used to give a total of 100%. Therefore, mixture range of 50:45:5 to 70:25:5 or 58.5:35:6.5 to 61.5:35:3.5 would meet the requirement.

Detector wavelength
  • Deviations from the wavelengths specified in the method are not permitted.
  • Stationary phase:
  • Column length: ±70%.
  • Column internal diameter: ±25%.
  • Particle size: Maximum reduction of 50%, No Increase    permitted.
  • Flow rate: When the particle size is changed, the flow rate may require adjustment, because smaller particle columns will require higher linear velocities for the same performance (as measured by reduced plate height). Flow rate changes for both a change in column diameter and particle size can be made by:

F2=F1x [(dc22xdp1)/( dc12xdp2)]

Where F1 and F2 are the flow rates for the original and modified conditions, respectively; dc1 and dc2 are the respective column diameters; and dp1 and dp2 are the particle sizes.

When column dimensions are changed, the flow rate may be adjusted using the following equation:

F2=F1x [(l2d22/( l1d12)]

Where F1 and F2 are the flow rates for the original and modified conditions, respectively; l1 and l2 are the respective column lengths; and d1 and d2 are the diameters.

  • Injection volume: Injection volume can be reduced as far as consistent with acceptance precision and detection limits; no increase is permitted.

Column temperature: ±10°C.      F2=F1x [(l2d22/( l1d12)]

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HPLC analysis and system suitability.

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HPLC Column Washing Procedure in best effective way

HPLC Column Washing Procedure; Purpose

The tenacity of this SOP is to define the procedure for washing of HPLC column to avoid any intrusion on repeated usage & to escalation column lifespan.

HPLC Column Washing Procedure; Scope

This procedure is applicable for all HPLC columns used within quality control laboratory of XX Pharmaceuticals Limited.

Definition: 
  • COA: Certificate of analysis
  • HPLC: High performance liquid chromatography
  • QC: Quality Control
  • SOP: Standard Operating Procedure
Responsibilities

The roles and responsibility is as follows

Senior Executive/Executive, Quality Control
  • To confirm that the instructions of this procedure are correctly followed.
  • To accomplish the HPLC column washing properly in accordance with this SOP.
  • To keep record of HPLC column washing time properly.
Manager, Quality Control
  • To confirm that this procedure is kept up to date.
  • To ensure that the SOP reflects the required working practices.
  • To assemble training on the SOP to all concerned personnel and to confirm implementation of the SOP after training.
Head of Quality Assurance
  • Take initiative to approval of the SOP.
  • To confirm the overall implementation of the SOP.
Procedure
  • Use HPLC grade solvents for column washing.
  • Freshly prepared, filtered and degassed solvent or solution should be used.
  • Purge solvent line to make them free from air bubbles.
  • Do not change flow rate at increment greater than 0.2 ml/min.
  • Keep column with proper end fitting during storage.
  • Do not over make tighter the column end fittings.
Pre-Wash (mobile phase run/ Prior to analysis) procedure
  • Set column on column compartment of HPLC.
  • Select shipping solvent, from COA of respective manufacturer, If not mentioned in COA, store the column based on column properties like Nitrile /ODS/Amine group etc.
  • Run shipping solvent (e.g. Azide solution, 65% Acetonitrile,) mentioned in COA of respective manufacturer for 15-20 minutes.
  • Gradually change the organic phase composition depending on the organic phase composition in mobile phase to reach the same in mobile phase. For example, gradually decrease the organic phase from 65% Acetonitrile (in shipping solvent) & finally reach 30% Acetonitrile (in mobile phase). For the Gradient HPLC this can be conducted through time program and for Isocratic HPLC, this can be done using intermediate solvents, as appropriate. Accomplish this run within 15 to 20 minutes.
  • Change line with mobile phase & execute HPLC analysis.
Post-Wash (mobile phase run /after completion of analysis) procedure
  • For mobile phase containing Buffer and counter ion
  • Replace mobile phase with purified water. Purge line. Run same for 15-20 minutes.
  • Depending on shipping solvent, gradually reach the same. For example, if 65% Acetonitrile is shipping solvent, then start with 100 % purified water and gradually increase the organic phase and finally reach at 65% Acetonitrile. For the Gradient HPLC this can be conducted through time program and for Isocratic HPLC, this can be done using intermediate solvents like 15%, 30%, 45% Acetonitrile, as appropriate. Accomplish this run within 55-60 minutes conducting each solvent composition period 15-20 minutes.
For mobile phase without buffer and counter ion

Depending on the shipping solvent, gradually reach the condition from the organic phase composition of mobile phase. For example, if 65% Acetonitrile is shipping solvent and organic phase composition in mobile phase is 30% Acetonitrile, then start with the initial organic phase of 30% Acetonitrile (70% Purified water) and gradually increase the organic phase and finally reach at 65% Acetonitrile. For the Gradient HPLC this can be conducted through time program and for Isocratic HPLC, this can be done using intermediate solvents as appropriate. Accomplish this run within 55 to 60 minutes conducting each solvent composition period 15 to 20 minutes.

 For mobile phase containing tri-ethyl amine
  • Replace the mobile phase with a mixture of methanol and 0.05% phosphoric acid (50:50 v/v) & run for 30 minutes.
  • Depending on the shipping solvent, gradually reach same. For example, if 65% Acetonitrile is storing solvent, then start with 20 to 30% Acetonitrile & gradually increase the organic phase and finally reach at 65% Acetonitrile. For the Gradient HPLC this can be conducted through time program and for Isocratic HPLC, this can be done using intermediate solvents as appropriate. Accomplish this run within 55 to 60 minutes conducting each solvent composition period 15 to 20 minutes.
  • Stop run. Remove column from HPLC unit, do end capping properly both ends &  place in respective column box.
  • Store column box in an allocated place.
  • Record HPLC column washing time after analysis in logbook for operation of HPLC.

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Entry and exit procedure for sterility testing area

Entry and exit procedure; Purpose

To detail the Standard Operating Procedure for Entry and Exit in Sterility Testing Area of XX Pharmaceuticals Ltd.

Entry and exit procedure; Scope

This SOP define the Entry & Exit Procedure of personnel who will get entry & exit in sterility testing area in Microbiology Laboratory of General Building at XX Pharmaceuticals Limited.

Definitions/Abbreviations

[] Not Applicable

Responsibilities
  • The roles and responsibility are as follows
  • Executive/Senior Executive, Microbiology
  • Follow the instructions of this procedure correctly.
Assistant Manager, Microbiology QC
  • To confirm that this mentioned procedure is kept up to date.
  • To confirm appropriate personnel from the section are trained on this procedure.
Head of Quality Assurance
  • Take initiative approval of SOP
  • To confirm the overall implementation of the SOP
Procedure

Instructions

  • Only certified, trained & validated employees can enter into the sterility testing area.
  • All employees are responsible to maintain their personnel hygiene & cleaning regularly.
  • To follow aseptic technique during change procedure
  • Always confirm sterility of the garments to be worn in the proper area.
  • Always confirm that sterile garments in the Laminar Air Flow dress cabinet.
  • The person infected by flue, cold, open lesions (i.e.: eczema) should not enter into sterility test area.
  • Confirm that AHU[Air Handling Unit] of sterile testing area is switched on at least one hour before starting testing in that mentioned area.
Step 01: Entry into Change room- 01 (Room no: GMB012, Grade: C)
  • Take away the whole garments (except undergarments), wrist watch, Jewelry, & any kind of ornaments after entering into the change room 01.
  • Personal/Street shoe must be put off into shelf of the step over bench. Cross step over bench & put on dedicated shoe kept into shelf of the other site.
  • Use 70% IPA from the IPA dispenser to rub Hand.
Step 02 : Entry into Change room 02 (Room Grade: C)
  • Put on a pair of sterile hand gloves very carefully.
  • Wear sterile primary gown having two parts (Trouser & shirts) & a hood to cover the hairs.
  • Rub the hands with 70% sterile IPA.
Step 03: Entry into Change Room 03 (Room Grade: B)
  • Take sterile garments from dress cabinet which was formerly kept into the dress cabinet in change room 03 of sterility testing area.
  • Put on sterile dress with sterile overall, head gear, face mask, Shoes, Sterile hand gloves & safety goggles and confirm aseptic clothing. The procedure of proper clothing is described below:
Putting on Gloves
  1. Open the bag of sterile cleanroom latex free gloves & fold out to expose folded cuff area of the gloves.
  2. Put on the glove by put in the fingers into latex free glove & pulling on the folded cuff area to cover the palm, confirming that only inside of the cuff is touched.
  3. With gloved fingers, fold gloves over the arms, pulling them up over the wrists & forearms, confirming that gloves endure its sterility.
Putting on Hood
  1. Open bag having sterile hood ensuring the contents remain sterile.
  2. With care & only touching inside of hood, turn hood inside out & place on the head, confirming that all head is covered & no bouffant cap is unprotected.
  3. Clasp hood around the neck by clipping self-possessed buttons under chin.
  4. Being cautious not to touch outside surfaces, adjust hood to cover all of head.
Putting on Mask

[] Put on facemask & by touching as minimal area as possible tie on mask & making sure it fits comfortably.

Putting on Safety Eyewear

[] Put on sterile safety eyewear glasses remain on isolated portion of Laminar air Flow of dress cabinet.

Putting on Safety Overalls
  1. Open bag having sterile overall, confirming innards remain sterile. Unfold left & right sides of overall.
  2. Taking top folded edge of overall unfold it towards you until it is lying flat to reveal full length of zipper.
  3. Take hold of upper edge of each leg inaugural & gather a handful of the garment in each hand, to catch up legs of overall.
  4. Continue to gather garment in this way so that when overall is held up it does not touch floor.
  5. Lifting overall, hold in front of you & step into one leg at a time, gradually releasing gathered fabric to allow each foot to push through.
  6. Take care not to allow arms of overall to touch floor.
  7. Pull overall up to waist height, taking care not to touch outer side of the overall.
  8. Slip hands into sleeves, one at a time & then slip remainder of overall over shoulders.
  9. Check that hood skirt is completely inside collar of overall & fasten overall with the zipper.
Step 04 : Entry into Sterility testing room 04 (Room Grade: B)
  • Spray gloved hands & wrists with sterile 70% IPA.
  • Flashing door with help of elbow, enter into sterility test room.
Step 05: Exit from testing room
  • After completion test remove used hand gloves put off into waste bin.
  • Rub hands with the help of 70% Iso Propyl Alcohol
  • Pull door to enter into change
  • Pull door to enter into second Change room then enter into first change room.
  • Take clean laboratory dress from cabinet put in the change room 01.
  • Send used garments to laundry for washing.
  • Enter information regarding entry exit procedures such as entry time, exit time, purpose,
  • Analyst name signature in log book, Annexure-I

Download Annexure Here

Annexure I Log book of Entry and Exit Personnel of Sterility Testing Area

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HPLC Column Management at best easy way

HPLC Column Management; Purpose

The tenacity of this SOP is to define proper controlling of all HPLC columns during receive, use and storage period to confirm that the HPLC column performs satisfactorily and gives reproducible results.

HPLC Column Management; Scope

This process is applicable for stock usage of HPLC columns required for Materials and Products analysis in quality control laboratory of general block of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[] QC: Quality Control.

[] HPLC: High performance liquid chromatography.

[] CoA: Certificate of analysis.

Responsibilities:

The roles and responsibility is as follows

Officer/Executive/Senior Executive, Quality Control
  • To confirm that this procedure is followed.
  • To maintain the records properly as per SOP.
Assistant Manager, Quality Control
  • To confirm that this procedure is kept up to date.
  • To ensure that the SOP is technically sound & reflects the required working practices.
  • Organize training on the SOP to all relevant personnel.
  • To confirm implementation of the SOP after training.
  • Schedule calibration of the instrument at the defined intervals.
Head of Quality Assurance
  • Initiative to take approval of the SOP.
  • To confirm overall implementation of this SOP.
Procedure:
  • Preserve column with appropriate end fitting during storage.
  • Prevent the column from any type of mechanical shocks.
  • Always use the column in the indicated direction.
  • Clean solvent reservoir filter in the mobile phase by sonication in the Methanol for 30 minutes, when required.
  • Test sample should be free from any type of particulate matter.
  • Stock review and raise requisition
Executive, QC will raise a purchase requisition considering the following elements:
  • Product & Method wise dedicated column.
  • New method related to Product Development which is in product launch pipeline for commercialization.
  • New Pharmacopoeia (BP, USP & EP) requirements.
  • Underprivileged system suitability performance of a column that has been triggered from HPLC column usage register and included in retired HPLC column register.
  • Executive, QC will make a list for purchasing of new columns on the basis of purchase requisitions to ensure uninterrupted HPLC analysis.
  • In-Charge, QC will finally review the list for purchasing of new columns by checking the HPLC column stock and issue and retired HPLC column register status or considering column requirement for new product.
Column receiving
  • Executive, QC will receive new column with CoA.
  • After receiving a new HPLC column, QC Executive will check the column CoA, specification & physical condition and compare with Purchase Order and Invoice description.
  • If complies with ordered description, then assign an individual column serial number (e.g. GQC-H001, where H represents HPLC column and 001 is the serial number) and record necessary information [Column receiving date, Column description (Name, brand, particle size and dimension etc.), Part number/ Catalogue, Manufacturer name, Supplier name, Column Sl. No., Column dedicated for (Product /Material), Column issue date etc.] in the HPLC column stock and issue register.
Column performance check for new column: HPLC Column Management
  • Check availability of reference reagents /standards required for performance test. If unavailable, then promptly raise requisition.
  • Carry out the column performance test for new HPLC column, as per manufacturer’s instructions. (If particular chemicals as per Manufacturer’s CoA are available.)
  • Check column with respect to Manufacturer’s CoA for retention time, theoretical plates using the material provided with the column & method specified by manufacturer.
  • In case of emergency carry out performance check only with the available reference standards/reagents.
  • Connect the column to HPLC system.
  • Flush (condition) specific column with shipping solvent (the details available with manufacturer’s CoA) or methanol for at least 30 minutes with a flow rate of 0.5 ml/min.
  • Flush column with mobile phase as mentioned in the technique for respective columns.
  • Prepare test solution in mobile phase as recommended in the procedure.
  • After column is conditioned, inject 20 µl or as per manufacturer’s CoA & record chromatograph of test solution.
  • Calculate tangent (theoretical plates) as per the USP method. The result should meet system suitability parameters.

Theoretical plate: (N) = 16 (t/W)2

Asymmetry (10%) = w/2f

Where, t = Retention time

W = Width of peak measured by extrapolating the relatively straight sides to the baseline

W = Width of peak at 10% of peak height

f = Distance between perpendicular dropped from apex of the peak and leading edge of peak at 10% of peak height

  • Keep records of the performance check on the HPLC Column Performance Check Record (as per Annexure-IV).
  • Accept column for use if observed values are within limit specified in manufacturer’s CoA.
  • Inform manufacturer through Purchase Department, if test result doesn’t comply with the accepted limit mentioned in the manufacturer’s CoA.
  • If problem is not resolved, reject same & information Purchase Department regarding rejection.
Material/Product Dedicated Column
  • In-Charge, QC will ensure method and/or product wise dedicated columns are available for HPLC analysis.
  • Same column can be used for analysis of two or more products in different dosage form where product formulation & active ingredients are same. But prior to use, method shall be validated using same column.
  • If dedicated column is not available, instantly discuss with In-Charge, Quality Control.
  • Column other than material and/or product dedicated column can be used in case of emergency with the concern of In-Charge, Quality Control.
Column Issue
  • Prior to issue a new column, review previous column history & record all information [Initial theoretical plates (Before issue), Column issue date, Issued by, Remarks] in the HPLC column stock and issue register.
  • If dedicated column is not available for a new material/product analysis, discuss the matter with In-Charge, QC for alternate decision.
  • All decisions shall be recorded in HPLC column stock and issue register (Annexure-I).
  • After issue, record the column information in a new page in HPLC Column usage register. (Annexure-II).
Column Care
  • Confirm that the integrity of the column packing is not be disturbed by needless opening of the column ends.
  • Handle HPLC columns as per manufacturers’ instructions, e.g. avoidance of physical shock, vibration and storage at high temperature.
  • For silica-based columns, avoid eluents outside the pH range of 3-8 where possible, except when column manufacturer specifications acclaim otherwise.
  • Wash column as per HPLC column washing procedure.
  • After use, wash the column to make it free from buffer salts with a suitable solvent (typically 1:1 aqueous/organic solvent for reversed phase columns) about 45 to 60 minutes maintaining a flow rate of 1.5 to 2.0 ml per minute.
  • After washing cap or seal column for storage in designated place.
  • In case of poor system suitability performance or column blockage caused by precipitation of buffer salts, always incorporate a flush with a solvent/water mixture before switching to pure solvent as per HPLC analysis and system suitability check procedure SOP No.: (SOP/QC/009).
  • Record the HPLC column flushing time in HPLC log book. Maintain HPLC column cleaning and storage as per manufacturer’s instructions.

Regeneration of a column

  • If the system suitability fails only then do the column regeneration.
  • For columns C6, C4, C18, C8, Phenyl, Amino, Polymeric follow the sequence given below with a 1.0 ml flow per minute flow rate.
  • Flush with filtered and de-gassed water for 30 minutes. Inject 20 µL of 1.0% of Acetic acid in purified water.
  • Flush with Methanol for 30 minutes, inject 20 µL of 1.0% Dimethyl Sulphonic Oxide (spectroscopic grade) in Methanol.
  • Flush with
  1. Acetonitrile for 15 minutes;
  2. Chloroform for 10 minutes;
  3. Methanol for 30 minutes sequentially;
  4. Isopropanol for 15 minutes;
  5. Purified water for 15 minutes
  • Check pH of water at inlet and outlet, which should be identical.
  • Mobile phase for the compound to be analyzed.

 

Retired HPLC Column

  • After washing, if the HPLC column performance is not improved then In-Charge, QC will review column washing process and column history prior to discarding/retiring a column.
  • The column retiring information must be recorded in the respective page of HPLC column usage log sheet (Annexure-II) and retired column register (Annexure-III).
  • Keep all retired columns under lock & key in a separate locker in the lab area. Before keeping analyst must ensure that the retired column has been separated from usage stock and de-shaped.
  • Periodically the HPLC column usage log sheet and retired column register shall be reviewed and retired column shall be destroyed as per column destruction process and manufacturers’ instructions.
  • Retired column storage period should not be less than last test product shelf-life plus one year.

Download All Annexure: HPLC Column Management

Annexure I HPLC Column Stock and Issue Register

Annexure II HPLC Column Usage Register

Annexure III Retired HPLC Column Register

Annexure IV HPLC Column Performance Check Record

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Waste Management in Quality Control Laboratory

Waste Management; Purpose

The purpose of this SOP is to describe the laboratory waste management procedure for disposal of test samples (raw materials, in-process, bulk/ finished product left over samples); expired retention samples (raw materials, finished product); broken glassware and glass container; packaging materials; all Laboratory chemicals & reagents used within the quality control laboratory.

Waste Management; Scope

This procedure is applicable to all laboratory operations associated with the disposal activity in the quality control and microbiology laboratory for general block at XX Pharmaceuticals Limited.

Definitions / Abbreviation
  • SOP: Standard Operating Procedure
  • QC: Quality Control
  • ETP: Effluent Treatment Plant
  • MSDS: Material Safety Data Sheet
Responsibilities

The roles and responsibilities are as follows

Senior Executive/Executive, QC & Microbiology
  • To ensure that this procedure is followed.
  • To identify correct sample for disposal.
 Asst. Manager, Quality Control
  • To ensure that this procedure is kept up to date.
  • To confirm that the SOP reflects the required working practices.
  • Arrange training on the SOP to all concerned personnel.
  • To ensure implementation of the SOP into routine use after training.
  • To ensure availability of adequate facilities, systems and resources to carry out this process and approve the SOP.
Head of Quality Assurance
  • Take initiative to Approval of this SOP
  • To ensure the overall implementation of the SOP
Procedure
  • Wear rubber gloves, mask, safety glass and footwear during disposal work.
  • Carry out the disposal work at the designated place.
  • Wash hands thoroughly with soap and water, at the end of the operation.
  • Always keep the waste bin covered with lids.
  • Destroy any label/carton/ foil before dumping into the bin for disposal.
  • Cross mark all label on the container with marker pen or destroy the label of container before disposal.
  • Use separate container for collecting the broken glass and transfer to the salvage yard-marking container as “BROKEN GLASSWARE”.
  • Do not return left over samples of raw materials, in-process material, bulk/ filled products to the container or work points from which it has been taken.
  • Keep all the waste in designated bin.
  • Carefully identify the name and check the status label of the sample to be disposed off.
  • Check the MSDS of raw materials for the hazardous identification and proper method of disposal.
  • Check the container properly for any left out material before disposition of the containers.
  • Use the sink of fume cupboard to drain out flammable, toxic, corrosive water-soluble solvent and all mobile phase.
  • Never light any type of flames & always place sign “No Flames” to warn others about the presence of Ether. Accumulate water immiscible solvents [like Chloroform, Dichloromethane, Carbon Tetrachloride, etc.) into one bottle & ether (Diethyl Ether waste) in another bottle & evaporate them separately using beaker by placing in fume cupboard.
  • Place hazardous solid waste (e.g. tissue paper, filter paper, cotton, contaminated gloves etc.) in dedicated bin/container.
  • Dispose liquid samples in sink by using large amount of tap water.
  • After completion of test, retain left over samples of raw materials, in-process material, bulk/ finished products with proper identification labeled as “UNDER TEST SAMPLE” in specified place the batch is approved.
  • After approval of the batch, transfer the excess samples (tablets, raw materials, capsules) of approved batch to a place labeled as “SAMPLE FOR DISPOSAL” record the disposal details in the Sample Disposal Register (Annexure-I).
  • Once in a month or when required, collect and destroy all samples for disposal following the above steps.
  • In case of raw materials, in-process material, and bulk/ finished products, empty out the sample from the poly bag into a container containing water, destroy the sample label of poly bag by shredding into “WASTE BIN FOR PAPER” & destroy the ploy bag in to the bin, labeled as “HAZARDOUS SOLID WASTE “.
  • Shake dispersion of sample in container with the help of a glass & allow disintegrating. After the complete disintegration, drain out slowly into designated place & clean the drain with adequate water flushing.
  • For stability sample after approval of report, analyst shall destroy the samples by dispersing them into a container having sufficient water and destroy the film, foil, de-blistered strips/blisters into a designated bin, labeled as “FILM/ FOILS FOR DISPOSAL”;
  • The secondary packaging materials (carton, leaflets, labels, shipper carton, master carton) into “WASTE BIN FOR PAPER” and other packaging materials (i.e. polyethylene bag, cap, plastic stopper, dropper etc.) into another bin, labeled as “PACKAGING MATERIAL FOR DISPOSAL”.
  • Shake the dispersion of sample in container with the help of a glass rod and allow to disintegrate. After complete disintegration, drain out slowly into designated place and clean the drain with adequate water flushing.
  • In case of ampoules, vials and bottles; break open the glass ampoule, open the vials and bottles, empty the contents in water and discard the broken ampoule and vial into a bin, labeled as “BROKEN GLASSWARE”. Shake the dispersion of sample in container with the help of a glass rod and allow to disintegrate. After the complete disintegration, drain out slowly into designated place and clean the drain with adequate water flushing.
  • Collect all types of waste from the respective bins into the different polythene bag by attaching “TO BE DISPOSED” label, weigh the waste content, and send waste to the salvage yard with a waste transfer note.

Download Annexure Here: Waste Management

Annexure I Sample Disposal Register

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Test solution and volumetric solution Preparation & standardization

Test solution and volumetric solution; Purpose

The tenacity of this procedure is to describe procedure for preparation & handling of test solution and volumetric solution.

Test solution and volumetric solution; Scope

This SOP is valid for preparation of chemical reagent in Quality Control Laboratory at XX Pharmaceuticals Ltd.

Definitions

N/A

Responsibilities

The roles and responsibility is as follows

Officer/Executive/ Sr. Executive, Quality Control
  • To confirm tests are performed with correct reagent as specified in method.
  • To confirm record of reagent preparation in the work sheet.
  • To confirm correct storage of reagent.
  • To confirm use of reagent within the shelf life.
  • To confirm reagents are retained until test results are approved.
  • To confirm use of log book.
Assistant Manager, Quality Control
  • To ensure reagents are in place and controlled.
  • To assess & disposition of expired reagent.
  • To maintain record.
  • To incorporate sound technical knowledge.
Head of Quality Assurance
  • To ensure the overall implementation of the SOP.
  • Take initiative to approval of the SOP.
Procedure

Precaution(s):

  • Wear protective clothing, gloves and goggles. Avoid contact with skin, eyes & clothing & inhalation of vapor.
  • Use a fume hood while preparing solutions.
  • Read label instructions of reagent container for any special precaution.
General
  • For solution preparation use purified water & analytical grade reagents & chemicals.
  • Prepare solution as per respective approved worksheet.
  • Calculate expiry date of solutions from date of preparation.
  • Check the following things before preparation of any solution.
  1. Glassware being used is clean & dried.
  2. Required reagents are available.
  3. Required instruments are calibrated.
  • Wear suitable safety appliances while making concentrated solutions of acid & alkali/any hazardous chemicals/substances.
 General guideline for the preparation of Test Solution
  • Enter details in test solution preparation register (as per Annexure-I)
  • Assign sequential reference number as below:
  1. g.TS-001/09/XX
  2. Where, TS is the abbreviation of Test Solution
  3. 001 is the sequential number
  4. / is separator
  5. 09 is the month of preparation (September)
  6. XX is last two digits of year 20XX
  • Affix respective label on container as per Annexure-III.
  • Expiry date of test solutions will be 06 months or as per mentioned in respective worksheet. During usage, any change in physical properties of the solution identified then discard it.
  • If a solution is directed to prepare “fresh” then it must be prepared on the same day of use
  • Discard the excess solution after expiry/ usage by diluting the solution with doubled quantity of water & then drain it into the drainage, and & entry on the respective worksheet & register.
General guideline for the preparation of volumetric solution
  • Analyst shall prepare all type of volumetric solutions as per respective worksheet.
  • Enter details in volumetric solution preparation register (as per Annexure-II)
  • Assign sequential reference number as below:
  1. g.VS001-001/08/XX
  2. Where, VS001 is the code no. of 0.1 M Ammonium thiocyanate VS
  3. 001 is the sequential number
  4. / is separator
  5. 09 is the month of preparation (August)
  6. XX is last two digits of year 20XX
  • Affix respective label on the container as per Annexure-IV.
  • Volumetric solutions and standard solution for limit test must not be store for more than three months. If during usage any change in physical properties of the solution identified then discard the solution.
  • Where stabilization time is not mentioned, stabilize solution for one hour before standardization.
  • Carry out standardization & calculate factor of the solution twice & RSD of two results must be within 0.2%
  • Find out the mean factor, which will be within ±5.0% of the labeled factor.
  • If factor of prepared solution identified more than ±5.0% variation, do the necessary dilutions/weight adjustments and carry out re-standardization. Report the factor upto four digits after decimal.
  • Solution should be re-standardized in 1 month +7 days interval. In case, where extraneous matters, layer separation or hazy solution observed then discard the solution.
Assign re-standardization reference number as below

e.g. Reference No./R1

Where, Reference No. of the volumetric solution subjected to re-standardization

/ is separator

R1 is re-standardization for first time (e.g. R1, R2…..)

Store all the solutions in cleaned dry containers & use amber color containers for light sensitive solutions.

Reject excess solution after expiry/ usage by diluting the solution with doubled quantity of water and then drain it into the drainage, and make entry on the respective worksheet & specific register.

Download all Annexure Here

Annexure I Test Solution Preparation Register

Annexure II Volumetric Solution Preparation and Standardization Register

Annexure III & IV Label for Test Solution & Label for Volumetric Solutions

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Chemicals and Reagents Management in Quality Control Laboratory

Chemicals and Reagents Management; Purpose

The tenacity of this SOP is to define the process for order, receipt, labeling, daily issue, stock control, handling, storage, labeling and expiry dating of all laboratory chemicals and reagents, solvents & solutions used within the quality control laboratory at XX Pharmaceuticals Ltd.

Chemicals and Reagents Management; Scope

This procedure is applicable to all laboratory chemicals & reagents, solvents & solutions used in the quality control laboratory at XX Pharmaceuticals Limited.

Chemicals and Reagents Management; Definitions / Abbreviation

[] ACS: American Chemical Society.

[] AR: Analytical Reagent.

[] GR: Guaranteed reagent.

[] MSDS: Material safety data sheet.

[] SOP: Standard Operating Procedure.

[] QC: Quality Control.

 

Reagent

Reagent is a substance which is added to a system in order to cause a specific chemical reaction, or added to notice if a reaction occurs or not.

Flash point

It is describe as minimum temperature of liquid at which it provides sufficient vapor to form ignitable mixture with the air.

Flammable liquid

Any liquid having Flash Point below 37.8⁰C[100 F]. Less-flammable liquids having flashpoint between 100 F & 200 F are well-defined as the combustible liquids.

HLF:

Highly flammable liquid having Flash Point of less than 32⁰C

Corrosive substance

A corrosive substance can be defined as which destroy or irretrievably damage human tissue when it comes into contact. Normally used corrosives are: Ammonium Hhydroxide, Acetic Acid, Chromic Acid, Hydrochloric Acid, Hydrotropic Acid, Hydrofluoric Acid, Nitric Acid, Perchloric Acid, Potassium Hydroxide, Phosphoric Acid, Sulfuric acid, Sodium Hydroxide.

YTD

Year-to-date. It can be defined as a period, starting from the beginning of the current year, and continuing up to the present day.

Chemicals and Reagents Management; Responsibilities:

The roles and responsibility is as follows

Officer/ Executive, QC
  • To raise requisition for & receive all laboratory chemicals & reagents maintaining proper procedure.
  • To confirm labeling with proper information, expiry dating of all laboratory chemicals, solvents, reagents and solutions after receipt or preparation.
  • To maintain daily issue, usage & all records properly as per SOP.
  • To confirm that procedures are followed during preparation of reagents & solutions.
  • To confirm that this procedure is followed.
Manager, Quality Control
  • To confirm that this procedure is kept up to date.
  • To check that the SOP reflects the required working practices.
  • To conduct training on the SOP to all concerned personnel & ensure implementation after training.
  • To confirm effective assessment for expiry dating of laboratory chemicals, reagents and solvents.
  • To track timely procurement of laboratory chemicals and reagents.
Manager, Quality Assurance
  • Take initiative to Approval of the SOP.
  • To confirm the overall implementation of the SOP.

Procedure:

Precaution(s):
  • Follow the relevant MSDS & safety guidelines while handling chemicals & hazardous reagents.
  • Proper protective clothing such as safety glasses, gloves & laboratory coat must be worn while handling chemicals in the laboratory.
  • Use fume hood while handling acids, bases, hazardous & flammables substances.
  • Try to minimum exposure to avoid contamination.
  • Use sonication to degas HPLC mobile phase before use.
  • Correctly label each unit container of chemicals & reagents.
  • Read reagent label very carefully before any type of use.
  • Don’t use any chemical or solvent when contaminated or change of physical appearance or precipitation observed.
  • Never ingest toxic substances.
  • Do not allow highly flammable liquids, toxic substances, corrosive substances to come into contact with the skin and eye.
  • Keep away flammables substances from fire or ignition source.
General guidelines
  • Never use beakers or measuring cylinders for precise volumetric measurement.
  • Always use class a glassware for all volumetric application.
  • Allow solutions temperature reduce to room temperature before any dilution to volume.
  • Always use clean, inert PTFE stirring bar as magnetic stirrer.
  • Reagent quality must be ACS[American Chemical Society] or AR or GR grade or equivalent, unless otherwise specified in relevant analytical method.
  • To prepare reagent solutions always use distilled water or purified water (that complies with USP/ BP/ EP requirement).
  • To avoid contamination even with best precaution, never return dispensed chemicals to stock bottle.
  • Before mixing solutions together, measure each solution individually.
  • Highly consumable like Methanol, maintain control of first in first out (FIFO) process.
  • Checked Expiry dates of reagent solution be before use.
  • To prevent contamination to the entire quantity and allocate the same expiry date as mentioned in the primary container, divide a large quantity of reagent into smaller containers. This is very useful for hygroscopic reagents.
  • Light sensitive reagent solution is to be kept in plastic bottles or amber glass.
  • Store chemicals in a designated place, away from heat or sunlight, return to the same location after each time of use.
  • Never store chemicals or waste in fume hood.
Ordering of reagents and chemicals
  • Review laboratory chemicals & reagents stock inventory on Monthly/Six monthly/Yearly basis / as when required.
  • Prepare a list for purchasing of new reagents & chemicals to ensure uninterrupted analysis in laboratory operations.
Raise a purchase requisition considering the following elements:
  • New method related to new product which is in product launching pipeline for commercialization of new product.
  • Reagents or chemicals with short self life expiry.
  • Pharmacopoeia (BP, USP & EP) requirements.
  • If possible, to avoid powder handling, Order toxic materials in liquid form.
  • Place requisition minimum three months earlier to the Procurement Department before the existing stock become nil.
Receipt of reagents and chemicals
  • Just after receipt, check integrity of the container & ensure reagents & chemicals are received its standard condition.
  • Check label on the bottle & tally with invoice / certificate / MSDS. If any discrepancy is found, report promptly to Store and Procurement Department.
  • After receipt, record receiving information at “Reagent and Chemical Receiving Register” as per Annexure-II & “Reagent Stock and Issue Register” for Liquid/Solid as per Annexure-III respectively.
  • Use ‘S- serial number’ for solid reagent & L- serial number’ for liquid reagent for reagent code numbering,.
  • Affix a reagent label to each unit primary container as per Annexure-VI.
  • Record the date of receipt & storage temperature mentioned on the label collected from manufacturer’s label/ certificate of analysis/ invoice. Assign the expiry date if found in manufacturer’s label.
  • Allocate the expiry date from the date of opening as follows, unless otherwise stated in manufacturer’s label,
  • Store reagents & chemicals in dedicated area where temperature at or below 30°C.
  • Keep large quantities solvents in the solvent store at room temperature unless otherwise stated in manufacturer’s label.

 

Chemicals and Reagents Management

 

Use of reagents and chemicals
  • Issue unbroken bottle/container from stock against requisition as per Annexure-I & maintain issue record (issued quantity/ issued by/date/balance amount etc. as required) into the ‘Reagent Stock and Issue Register’ for Liquid or Solid as per Annexure-III.
  • On the basis of critical stock position, raise requisition for chemicals & reagents to procurement department.
  • Allocate opened date/expiry date sign on the previously affixed label for newly opened container.
  • Not issued bottle/containers must not be mix with the opened bottle/container.
 Handling and storage of Toxic substances, highly flammable liquids

Toxic substances:

  • All toxic substances/chemicals to be labeled as toxic & handled under fume cupboard.
  • For weighing dry toxic powder, use container with lid. Add approximate amount of powder to the container & close lid in a fume hood. Back to the balance & weigh the powder. Back to the fume hood to prepare solution.
  • Keep container closed as soon as possible with tightly fitting.
  • Low dilute solution (<1% w/v) of toxic substances may be handled in the laboratory with appropriate care to avoid contamination of the area & individuals.
  • All vessels/containers used for long-lasting storage of toxic substances/chemicals must be carefully labeled with the contents & hazard type.
  • Vinyl/nitrile/latex gloves must be worn while handling toxic substances/chemicals. Properly fitted mask must be use to handle handling solid toxic substances.
  • Adequate care should be taken during removing of PPE [Personal Protective Equipment] to avoid contamination of the hand/face.
  • All contamination by toxic substances/chemicals must be washed off/cleaned up instantly as per instructions/guidelines/protective measures mentioned on MSDS [Material Safety Data Sheet].
  • Disposal of toxic substances/chemicals must be conduct with extra care.
 Highly flammable liquids
  • Majority of laboratory solvents and certain flavors, essence & film coating solutions are highly flammable liquids

can cause serious fires & explosions with subsequent injury to personnel & damage to goods.

  • Must be stored in the isolated place of Solvent store area.
  • An intact bottle shall be transferred to the laboratory by maintaining a record/requisition.
  • Stored quantity in the Laboratory/ Production area must not exceed 20 litres.
  • To avoid accumulation of vapor, must be stored in a suitable well ventilated place.
  • Must be handled in a well-ventilated area such as a fume cupboard in the Laboratory.
  • A suitable carrier to be use during carrying of Bottles to minimize the risk of breakage.
  • Containers should not store in direct sunlight/near a source of heat/ignition. Store the containers in the isolated place on a metal/solvent resistant tray.
  • Never use in the same working area near undressed flame, hot plate/any equipment that is legally responsible to produce a spark.
  • Container must be closed at all times other than when the liquid is being transferred from it.
Download all Annexure Here: Chemicals and Reagents Management

Annexure I Requisition Form for Laboratory Chemicals and Reagents

Annexure II Reagent and Chemical Receiving Register

Annexure III Reagent Stock and Issue Register

Annexure IV List of Toxic Laboratory Chemicals

Annexure V List of Flammable Solvents

Annexure VI Label for Reagent

 

 

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Handling of spillage in quality control laboratory

Handling of spillage; Purpose

The tenacity of this SOP is to define the handling of the spillages in the quality control laboratory to make laboratory safe, neat & clean.

Handling of spillage; Scope

This process is applicable to the chemical room, instrument room in the quality control laboratory of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[] MSDS: Material Safety Data Sheet

[] SOP: Standard Operating Procedure

[] QC: Quality Control

[] Spillage: The act of allowing a fluid or material to escape from the container.

Responsibilities

The roles and responsibility is as follows.

Lab attendant, QC

[] To clean-up the spills maintaining proper procedure.

Officer, QC

[] To ensure that this procedure is followed.

Manager, Quality Control
  • To confirm that this process is kept up to date.
  • To confirm that the SOP is reflects the required working practices.
  • Place training on the SOP to all concerned personnel.
  • To confirm implementation of the SOP after training.
Head of Quality Assurance
  • Take initiative to Approval of this SOP.
  • To confirm the overall implementation of the SOP.

 Procedure:

Precaution(s):
  • Carefully handle the solvents & chemicals to avoid accidents & spillages.
  • Use gloves, mask & eye protector while handling spillage.
  • Be watchful while neutralization process of acid or base spills because it may be enthusiastic, cause splashes & yield large amount of heat.
  • For spillage of flammable liquids, control all potential source of ignition near spillage area.
  • Never generate dust or cause the contaminated powder to become airborne while cleaning of solid spills.
  • If broken glass is involved, never pick it up with gloved hand rather than use tongs.
  • Ensure that all forms of local exhaust i.e. fume hoods are operating.
  • Water shouldn’t be used for chemicals which are water reactive.
  • Never use a vacuum cleaner to clean up the spill.
  • On spillage, personnel who caused the spill will instantly inform supervisor, all persons in the laboratory to take care & the lab attendant to clean spillage.
  • Evacuate the specific area, if required.
  • Limit access to spill area until total cleanup is completed.
  • For water spillage use only mop with dry cloth.
  • Wear suitable PPE[personal protective equipment] e.g. gloves, goggles, masks etc. while cleaning up spills.
  • Use tongs to pick-up the broken glass, when spills involve broken glass, place it in plastic dustpan to place them in the bin dedicated for broken glassware.
  • Use brush & the plastic dustpan to place materials into polyethylene bags & dispose it as chemical waste when spillage of solids.
  • If spillage occurs due to liquids like acids or solvents, mop it up clearly.
  • When needed, add adequate quantity of absorbent silica or precalcinated silica granules and let stand for few minutes, collect the material using hand gloves into polyethylene bags & dispose it as chemical waste.
  • If needed, use sodium bicarbonate to neutralize acids. Use pH paper to check pH when acid spills have been neutralized. Then mop it up with water.
  • For spillage of liquids like alkali, add adequate quantity of water to dilute it, mop with the help of dry cloth and finally wipe with wet cloth.
  • In case of Mercury spills, begin cleanup procedure with collecting the droplets of mercury. The large droplets can be consolidated by using scraper or a piece of cardboard. For cleaning up small mercury droplets, pick up with a piece of adhesive tape. Slowly & carefully squeeze mercury onto a damp paper towel. Place paper towel into polyethylene bags & dispose it as chemical waste.
  • While cleaning the area where spillage of hazardous chemicals & poisonous take precautions as per MSDS of respective chemicals.
  • After bulk of the material is cleaned up, wipe up the area with previously mixed detergent water & then with tap water and then leave the area to dry.
  • Rinse tools (plastic dustpan, tongs etc.) off plentiful amount of water.
  • Dry tools off & keep in isolated place.
  • Dispose of gloves as waste and place goggles back into the dedicated area.

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Chemical laboratory safety procedure, how to maintain it?

Chemical laboratory safety procedure; Purpose

Chemical laboratory safety procedure, The tenacity of this SOP is to define the general laboratory safety procedure, which will confirm the safe working condition within the Quality Control Laboratory.

Chemical laboratory safety procedure; Scope

This practice is valid for laboratory operations in the quality control laboratory of XX Pharmaceuticals Limited.

Definition

[] MSDS: Material safety data sheet.

[] PPE: Personal protective equipment.

[] QC: Quality Control.

[] SOP: Standard Operating Procedure.

Responsibilities:

The roles and responsibility is as follows

User/Analyst

[] To use personal PPE [Protective Equipment] as per MSDS [Material safety data sheet].

[] To maintain appropriate procedure for safety.

Manager, Quality Control
  • To confirm that this procedure is kept up to date.
  • To check that SOP reflects required working practices.
  • To organize training on the SOP to all concerned personnel.
  • To confirm implementation of the SOP after training.
  • To achieve the operational control.
  • To confirm the availability of suitable PPE & safety equipment.
Head of Quality Assurance
  • Take initiative to Approval of the SOP.
  • To confirm the overall implementation of the SOP.

Procedure:

Precaution(s):

  • Take a note of material hazard facts from the supplier’s information. Review any relevant hazard data in MSDS.
  • Do not smoke, drink, chew gum, eat, or apply cosmetics in the laboratory.
  • Do not keep food or beverages in the laboratory.
  • Always keep the flammable chemicals away from sources of fire.
  • Try to avoid unnecessary chemical exposure.
  • Never use fume hood for storage.
General procedure
  • Wear laboratory coat and dedicated laboratory shoes, before entering into the laboratory. Keep goggles/ eye protector in the pocket of lab coat and & when necessary. This will give protection against corrosive action of chemicals & contaminations.
  • Check PPE prior to use & attire appropriate protective equipment as processes dictate & when required to avoid chemical exposure.
  • Wear gloves when using any type of hazardous or toxic chemicals & respirator when handling solvents.
  • Wash & clean gloves regularly during a hazardous job. Discard soiled gloves as hazardous waste after use. Remove them before leaving laboratory/at the end of the work.
  • When handling/transferring solid chemicals only from one container to another, wear gloves dust mask and activity to be perform under fume cupboard.
  • Treat anonymous chemicals as hazardous & before starting work, make sure the analysts are familiar with all known hazards of the chemicals & take proper precautions.
  • Reject glass apparatus that is damaged, cracked/even scratched.
  • Examine all glassware before use. Use washed & clean glassware. Always move gas cylinder on cylinder trolley. Gas cylinder when standing upright position should always be appropriately supported.
  • Use fume hood to handle hazardous chemicals, volatile liquid and flammable compounds.
  • If solvent extraction is perform by shaking in a separating funnel, release pressure at frequent intervals by reversing funnel. Point the funnel away from the eyes & naked flames.
  • Avoid pipetting anything by mouth. Use mechanical pipetting device/pipette bulb/ aspirator.
  • Always add the acid to the water when diluting acids; never add water to acid. Add the acid to water slowly.
  • Conduct periodical inspection in laboratory refrigerators & storerooms, correctly label all collected samples.
  • Confirm all electrical wires are properly insulated. Report all electrical faults to the reporting authority/supervisor.
  • Instantly Report all type accidents to the Supervisor/Manager.
  • Confirm that all personnel engage laboratory know about the fire exit from the chemical laboratory.
  • Confirm eye showers & Fire extinguishers are located at easily accessible points.
  • Confirm all personnel/user are aware about the locations & proper use of all safety equipments (e.g. eye shower, First-aid kit, fire extinguishers).
  • Wash hands before leaving the laboratory, in case of chemical handling.
  • Wash the exposed area with large amount of water in case of spillage of any acid, base or irritant material on skin and seek immediate medical support if required.
  • Clearly sealed& labeled the dangerous materials and never leave it on the working bench unattended
  • Visitors to laboratory should be under the direct supervision of a accountable personnel.
Spillages
  • Spillages must be instantly dealt as per SOP for Handling of Spillages in the QC Laboratory.
Disposal of waste
  • Waste must be disposed as per SOP for Waste Management in QC Laboratory.

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Air Borne Particle Counter Operation

Air Borne Particle Counter; Purpose

To describe a standard operation, Cleaning & Calibration procedure of Air Borne Particle Counter.

Air Borne Particle Counter; Scope

Procedure is applicable to Air Borne Particle Counter of at XX Pharmaceuticals Limited.

Definition/Abbreviation:

Particle counter: An analytical device to count non-viable particles of specific sizes.

IPA : Isopropyl Alcohol.

Responsibilities:

The roles and responsibility is as follows:

Microbiologist

[] Follow the instructions of this procedure correctly.

Asst. Manager, Microbiology/QC

[] Ensure that SOP is technically sound & reflects the required working practices.

[] Confirm this procedure is kept up to date

Head of Quality Assurance

[] Take initiative to Approval of SOP.

Procedure

Instructions

[] Never use IPA on the display to wash it.

[] Don’t let the verification filter to be moistened.

[] Use your finger dab directly, don’t uses your nail on touch screen.

Operation
  • Turn on power switch.
  • Press “CONFIG” for “DATA SETUP”.
  • Select particle size with pressing “PARTICLE” option.
  • Select the particle size for another date setup then Press” BACK “option
  • Press ” SAMPLE” option for delay time, sampling time, sampling volume and no. of cycle setup then pressing “ENTER” for saving input.
  • To go to main display, Press ” BACK” option.
  • For manual mode or automatic mode, Press “SETTING”
  • For counting the particle, Press the “START” option.
  • Depending on room size, calculate number of sample.
  • Go to main the display
  • Press “CONFIG “
  • Pressing” LOCATION” option, Select Location.
  • Press” EDIT “option, if required to add new location.
  • To go to main display, Press the “BACK” option.
Set Location & Recipe
  • Go to the main display
  • Select the “CONFIG” option
  • Select the “RECIPE” option
  • Select the location
  • Write location name
  • Select the particle size
  • Select sampling time & sampling volume
  • Write down desired volume.
  • Select delay & set delay time (Initial one is 05 second by default).
  • Enable print average if needed
  • Select Auto print (if needed)
  • To go to main display Press “BACK” option.
  • Top count the particle, Press the “START”.
  • Completion of counting cycle is stopped automatically.
  • Then press “START” option for another cycle & counting the particle.
  • Take Print When Auto print option is disable
  • Go to the Main Display.
  • Press “DATA” option
  • Press” RANGE” option
  • Pressing “MAIN” option, Go to main display
Verification Test( Zero Count Test)
  • Go to the Main Display
  • Click on the Sampling Button
  • Select the location (Location should be 5)
  • Write Zero count test
  • Select time (1minute)
  • Select Unit( Ft ³ )
  • Select the Zero count test
  • Select the Sample
Cleaning

[] Clean Air Borne Particle Counter with & pipe with a piece of clean cloth

[] Use 70% sterile IPA damped cloth to clean it.

[] Clean the Display only with a clean sterile dry cloth.

Calibration Procedure

[] Contact with the supplier to the equipment to calibrate as per schedule.

[] Perform the calibration yearly or as per supplier instructions.

Download Annexure Here

 Annexure I Air borne particle Counter Logbook

Air Borne Particle Counter Operation Read More »

Water Bath, Operation, Calibration and Cleaning

Water Bath; Purpose

The tenacity of this SOP is to define the operation, calibration & cleaning of Water Bath

Water Bath; Scope

This procedure is applicable for Water Bath installed in Microbiology section at XX Pharmaceuticals Limited.

Definitions/Abbreviations

LED: Light Emitting Diode

Responsibilities:

The roles and responsibility are as follows

Executive/Senior Executive, Microbiology
  • To confirm that the instructions of this procedure are properly followed.
  • To maintain the record correctly as per SOP.
  • To confirm cleaning of shaking water bath maintaining safety guidelines.
Assistant Manager, Microbiology
  • To confirm that this process is kept up to date.
  • To ensure that the SOP is technically sound & reflects required working practices.
  • To arrange training on the SOP to all concerned personnel & to ensure implementation of the SOP after training.
  • Schedule calibration of the instrument at the defined intervals.
Procedure
Instructions
  • Laboratory coat, hand gloves & safety glasses must be worn while handling instrument.
  • Never touch the liquid within the bath as it may be very hot.
  • Each time use the display or a thermometer to check the temperature.
  • Never block ventilation slots during operation.
  • Each time disconnect bath from electricity supply before cleaning.
  • Allow the liquid in bath to cool down to 40°C before draining.
  • Use only purified water, never operate water bath without water.
  • Fill the it prior to connection to power supply.
  • It should be covered with a lid or polypropylene spheres to achieve optimum performance.
  • Always use the stainless steel flat lid with concentric rings when the instrument is not in use to avoid contaminants landing in the bath liquid.
  • Don’t touch any electrical contacts or open any closure panel that may be risk of electrical shock when above 60˚C or below room temperature,
Operating Procedure
  • Check the calibration date of the instrument before each time use. If the calibration is out of date, calibrate it and then use.
  • Check water level, If require adjust the water bath to an appropriate level with purified water.
  • Switch on the power from the main.
  • Using the switch “I” ON, “O” OFF button located at the rear side of it, Switch on the Water bath When ON (I) the switch is illuminated & unit performs a self-test where all segments of the 3 digit LED display & indicators illuminated.
  • To display “SP1” to set temperature, press & hold down key for more than 1.5 seconds. “SP1” will show blinking.
  • To select required temperature, use up or down arrow keys.
  • Heater indicator will illuminate. Wait until the display flashes between “SP1” & set temperature and will revert to show actual liquid temperature.
  • When the bath temperature is either 4°C above or below set temperature, LED indicator will illuminate.
  • Open concentric ring & place beaker or suitable container with sample on sphere of it.
  • After completion of work, switch off bath by using “I” ON, “O” OFF switch, located at rear side of back of it.
Calibration Procedure
  • Calibrate Water bath once in a year.
  • Fill purified water in water bath to an suitable level.
  • Switch on the bath using “I” ON, “O” OFF switch, located at the rear side of back of the Water bath.
  • Set desired temperature against calibrated standard thermometer at 35⁰C, 45⁰C, 65⁰C.
  • Wait 30 minutes to equilibrate.
  • Verify temperature using a calibrated standard thermometer & record the temperature in the Calibration information sheet for Water bath (as per Annexure-I).
Cleaning Procedure
  • When water becomes dirty, clean instrument otherwise clean once in a week.
  • Switch ‘OFF’ the instrument.
  • Disconnect main power supply.
  • Open stainless steel flat lids with concentric rings of the water bath.
  • Use purified water to wash the stainless steel flat lids and concentric rings.
  • To reduce potential biological contamination, remove the water from water bath.
  • Wash it with soapy water & then purified water.
  • Mop with clean dry cotton cloth.
  • To remove any deposits, use 10% nitric acid on a cloth (wear suitable gloves).
  • Gently heat to 50°C for an hour after adding 1 liter of vinegar to water in the stainless steel tank, empty and brush the lime away for descaling then rinse thoroughly afterwards.
  • Fill with purified water up to desired level .
  • Close the stainless steel flat lids with concentric rings.

 Download Annexure Here

Annexure I Calibration Information Sheet for Water Bath

Water Bath, Operation, Calibration and Cleaning Read More »

Cooled incubator, Operation, cleaning and calibration procedure

Cooled incubator Purpose

To operate, clean and calibrate Cooled Incubator in order to support the growth of Yeast and mould in Microbiological analysis.

Cooled incubator Scope

This SOP applies for operation, cleaning and calibration of Cooled Incubator, Model: ICP600 in Microbiology Section of at XX Pharmaceuticals Limited.

Definitions/Abbreviations

N/A

Responsibilities

The roles and responsibility is as follows

Executive/ Senior Executive, Microbiology

Operation, cleaning & calibration

Assistant Manager, Microbiology

Ensure Operation, cleaning, calibration and application of sound information.

Head Quality Assurance

Take initiate to approval of SOP

Procedure:

Instructions

  • Do not wipe with damped cloth at on position.
  • Use only 70% IPA or ethanol to wipe chamber
  • Do not overload chamber with tested items.
  • Do not keep items those may produce inflammation with air.
  • Keep all tested items to avoid touch inner surface of the chamber.
  • Do not move the Cooled Incubator at on position. Severe vibrations may cause serious damage of the temperature probes.
Operating Procedure
  • Press push/turn control key to put on main power switch in front of instrument. The Cooled Incubator will start in normal mode with display of timer, chamber temperature, alarm temperature (red color indication).
  • Hold down SET key & turn the push/turn control key at the clockwise or anti clockwise for setting date, local time, operating temperature at [23.5± 2.5]0C, alarm temperature at 300 After setting, SET key will be released the display briefly flashes the set point. The display then changes to the actual current temperature and starts to the setting temperature. The temperature will be automatically increased at setting temperature and display the setting temperature digitally.
  • Observe the display temperature until stable position.
  • Hold down the SET key (approximately 3 seconds) to select the operation mode, if require. The current operating mode will be flashed on the display. There are three operating mode in the Cooled Incubator:
  • Normal Operation
  • Weekly Programmer
  • Ramp time Programme Operation
  • Select required programme and set as per operation manual.
  • Select fan speed to set air changes. Selected position of fan speed will show in display.
  • Turn the push/turn control at clockwise until fan symbol flashing to move the air slider opens and closes the air valve to control the supply and discharge of air.
  • Check chamber temperature using by a calibrated digital thermometer, when the setting Temperature reaches.
  • Keep the required materials inside the chamber.
Cleaning & Disinfection :
  • Switch off Cooled Incubator and disconnect the power plug.
  • Remove all test flasks and others items from chamber.
  • Clean inside of chamber initially with dry cloth and wipe finally with 70% IPA wetted cloth.
  • Clean outside of chamber with dry cloth.
  • Disinfect all surfaces with 5% Savlon solution and dry the outer surface.
  • Reload all items into chamber when reach to dry the chamber surface.
  • At the end of cleaning, connect the power plug and switch on.
  • Clean the chamber once in a month.
  • Clean the outer surface every day.
 Performance Check
  • Check chamber temperature daily once.
  • Record chamber temperature in Daily temperature Record
  • Temperature range ± 2.5C from the set temperature.
Calibration of Cooled Incubator
  • Insert standard thermometer or thermocouples into chamber.
  • Place at different location of chamber at least 6 position.
  • Press & hold down SET key until the normal mode light blinking.
  • Turn push/turn control key clock wise to reach SETUP light.
  • Select Calibration to rotate push/turn control key.
  • Use three calibration temperatures as below :
  • 1 : 150C
  • 2 : 220C
  • 3 : 300C
  • Select required calibration temperature in SETUP key & set the corresponding calibration correction to 0.00
  • Measure deviation from selected calibration temperature under the steady conditions, using a reference instrument.
  • Set calibration correction in SETUP key. If the measured reference temperature is too low, the calibration correction setting is negative sign.
  • Adjust temperature if require from adjusting value of calibration temperature (CAL). The correction value should not more than ±10C.
  • Carry out check measurement using the reference thermometer.
  • Carry out others two calibration temperatures in the same manner.
  • Calibrate the incubator once in a year ± 15 days.
  • Record calibration in Calibration Record, as per Annexure-V of Engineering SOP
 Maintenance
  • If Cooled Incubator shows any mechanical, electrical or any others problem, inform to supplier or Engineering Department for corrective action.
  • After corrective action, recalibrate Cooled Incubator.

Download Annexure Here

Annexure I Cooled Incubator Operation Log Book

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Oven Operation, cleaning and calibration procedure

Oven Purpose

To dry all properly cleaned glassware which is subject to use in chemical analysis & also to sterilize cleaned glassware which is subject to use in different microbiological analysis.

Oven Scope

This SOP applied for operation of Oven, which model is: UNE600 in QC Section, Microbiology Section & Product Development Section of at XX Pharmaceuticals Limited.

Definition/Abbreviation

N/A

Responsibilities

The roles and responsibility is as follows

Executive, Microbiology/ Executive, QC

Operation, cleaning & disinfection and performance checking of oven.

Assistant Manager, Microbiology
  • Ensure Operation, cleaning & disinfection and performance checking.
  • Ensure that oven is calibrated.
  • Checking that SOP is technically informative.
Head of Quality Assurance

Take initiative to Approval of SOP

Procedure
Instructions
  • Never enter open hands in the chamber of oven.
  • To keep or remove glassware, wear temperature resistance gloves.
  • Avoid to keep glassware into chamber with water or any other solution.
  • Do not dry plastic materials using oven.
  • Always keep door closed & avoid opening door for long period.
Operating Procedure
Sterilization of Glassware for Microbiological Analysis
  • To put on the main power switch, Press push/turn control key in front of the instrument. Oven will start in normal mode with the display of the chamber temperature, timer, alarm temperature.
  • Turn the push/turn control key by hold down the SET key & at the clockwise or anti clockwise for setting date, local time, operating temperature, alarm temperature. After setting, SET key will be released the display briefly flashes the set point.
  • To select the programme, Press & hold down SET key and rotate push/turn control key at clockwise and select “Ramp timer” mode.
  • Set the work days group using the push/turn control by holding down the SET key and Press push/turn control to select the ramp segment “t1” If the day is not required, it will be off position.
  • Set the time using push/turn control by hold down the set key &
  • Use the push/turn control, to Select ramp segment “t2”. Hold down SET key and using the push/turn control set the time.
  • Until the temperature display is flashing, Turn push/turn control clockwise. Set the required temperature setpoint using push/turn control
  • Select setpoint waiting time by hold down the SET key. Hold down SET key and set on using the push/turn control. After the SET key has been released the function for setpoint waiting time is stored.
  • Hold down SET key & set time using the push/turn control then Select hold time “t3”.
  • Hold down SET key & set time using push/turn control after selecting cooling time “t4”.
  • Select program repeats “loop”. Hold down the SET key and set 2 for repeats using the push/turn control.
  • To set the air changes, select the fan speed. Turn the push/turn control clockwise until the fan symbol is flashing. Set fan speed 50% suing the push/turn control holding down the SET key.
  • Turn the push/turn control clockwise until monitor temperature display is flashing. Set the alarm temperature using the push/turn control holding down the SET key & select alarm temperature.
  • Turn push/turn control at clockwise until the fan symbol flashing to move the air slider opens & closes the air valve to control the supply and discharge of air.
  • Turn the push/turn control clockwise until the stop symbol ▀  is flashing. Select start ► using the push/turn control holding down the SET key and On releasing the SET key the program starts to run
Glassware Drying
  • To put on main power switch. Press push/turn control key in front of the instrument. The oven will start in normal mode with display of chamber temperature, timer, alarm temperature.
  • Select operating mode “Normal operation” holding down SET key (approximately 3 seconds) the current operating is flashing.
  • Select temperature set point by hold down the SET key & use the push/turn control to select required temperature set point. After the SET key has been released the oven briefly flashes the temperature setpoint. Heating is indicated by the orange heater symbol.
  • Select fan speed. Turn push/turn control clockwise until fan symbol is flashing while the holding down the SET key. To set 50% fan speed use the push/turn control
  • Turn the push/turn control clockwise until the monitor temperature display is flashing. Select the alarm temperature. Use the push/turn control to set the alarm temperature by holding down the SET key.
  • The display then changes to the actual current temperature and starts to the setting temperature. The temperature will be automatically increased at setting temperature and display the setting temperature digitally.
  • Observe the display temperature until stable position.
  • Remove dried glassware from oven at the end of drying,
Cleaning of Oven
  • Clean the inner benches of Oven with a cleaned cloth.
  • Use 70% IPA or ethanol to disinfect the inner surfaces.
  • Clean the outer surfaces with dry cleaned cloth.
  • Disinfect the outer surfaces with 5% Dettol /Savlon solution.
Calibration of Oven
  • Insert standard thermocouples or thermometer into the chamber.
  • At least 6 position to be consider to place different location of chamber.
  • Press & hold down SET key until the normal mode light blinking.
  • To reach SETUP light, turn push/turn control key clock wise.
  • Select Calibration to rotate push/turn control key.
  • Use the following temperature for calibration:
  • 1 : 1500C
  • 2 : 2000C
  • 3 : 2500C
  • Select required calibration temperature in SETUP key & set the corresponding calibration correction to 0.00
  • Under the steady conditions, using a reference instrument, measure the deviation from the selected calibration temperature.
  • If the measured reference temperature is too low, the calibration correction setting is negative sign, set the calibration correction in SETUP key.
  • The correction value should not more than ±10C.
  • Adjust the temperature if require from adjusting value of calibration temperature (CAL), carry out the check measurement using the reference thermometer.
  • Carry out others two calibration temperatures in the same manner.
  • Calibrate incubator once in a year.
  • Record calibration in Oven Calibration Record, Annexure-II.

Maintenance

Inform to supplier or Engineering Department for maintenance, If Oven shows any mechanical, electrical or any others problem, after maintenance, recalibrate the oven.

Download all Annexure here

Annexure I Oven Calibration Record

Annexure II Oven Log Book

 

 

Oven Operation, cleaning and calibration procedure Read More »

Vortex Mixer; Operation and Cleaning Procedure

Vortex Mixer; Purpose

To establish the procedure for ideal operation and cleaning of Vortex Mixer, Model: Genius 3 KIA, Fisher Scientific, UK in microbiology test.

Vortex Mixer; Scope

This SOP applies for operation, cleaning of Vortex Mixer, Model: Genius 3 KIA, Fisher Scientific, UK in Microbiology Section at XX Pharmaceuticals Limited.

Definitions/Abbreviations

NA

Responsibilities

The roles and responsibility is as follows:

Executive/ Senior Executive, Microbiology

Operate & clean of Vortex Mixer.

Asst. Manager, Microbiology

  • Ensure Operation, cleaning & application of sound technical information.
  • Keep the up to date of SOP.
  • Review that SOP is technically informative.
Head of Quality Assurance

Take initiative to Approval of SOP

Procedure:
Instructions
  • Do not press hardly on platform.
  • To avoid movement during vortex, keep Vortex Mixer in a fixed place.
  • Do not vortex any materials for long time.
  • To avoid overflow during vortex, maintain the level of test solution into test tube/Vial/test flask.
 Operation Procedure
  • Switch ON the power button. The red indicator light will be illuminated.
  • Press SET switch to select the automatic vortex or manual vortex.
  • Set time to press TIMER button as per requirement.
  • Adjust vortex speed by turning SPEED button at clockwise for increasing or anti clockwise for decreasing.
  • Place test tube/vial/test flask on the platform.
  • Attach tube/vial with the machine for more than 1 minute vortex.
  • Press START button if set manual vortex.
  • Touch test tube/vial on platform to start the vortex automatically.
  • Remove test tube at the end of vortex.
  • Switch OFF power button.
  • Disconnect machine.
  • Press MAINS switch off.
Cleaning Procedure
  • Switch off Vortex Mixer and disconnect the power plug.
  • Clean outer surface with dry cloth.
  • Disinfect outer surfaces of Microscope with 5% Dettol/Savlon solution.
  • Clean daily once.

Maintenance

Inform to supplier or Engineering Department for repairing, If Colony counter shows any mechanical, electrical or any others problem.

Vortex Mixer; Operation and Cleaning Procedure Read More »

Colony counter Operation and cleaning procedure

Colony counter; Purpose

To establish the procedure for ideal operation and cleaning of Colony Counter, Model: SC6, Stuart UK, in microbiology test.

Colony counter; Scope

This SOP applies for operation and cleaning of Colony Counter, Model: SC6, Stuart, UK in Microbiology Section of General Building at XX Pharmaceuticals Limited.

Definitions/Abbreviations

N/A

Responsibilities

The roles and responsibility is as follows

Executive/ Senior Executive, Microbiology

Perform operation & cleaning.

Manager, Microbiology

Confirm that operation is carried out properly.

Keep the SOP up to date.

Review that SOP is technically informative & application of sound knowledge.

Head of Quality Assurance

Take initiative to Approval of this SOP

Procedure:
Instructions
  • Do not press hardly on counting platform.
  • Do not use any concentrate cleaning or disinfection solution to outer surface of machine.
  • Do not open petridish during colony counting because all micro-organisms are unscrupulous pathogen.
  • Cover with a pack of clear discs to protect receiver plate from dust and scratches.
Operation Procedure
  • Turn on unit pressing by <ON/OFF> switch located at back of the unit.
  • Select plate receiver background as per requirement either dark or white pressing by side panel.
  • Select appropriate adaptor for use of less than 90 mm petridish & place it on the receiver plate.
  • Adjust sensitivity turning the control knob at clockwise for increasing and at anticlockwise for decreasing.
  • Place covered Petridish on receiver plate, using centering adapter if required.
  • Press & hold the <correct/reset> key to ensure display is set to zero before counting.
  • Mark on each colony with a felt tip pen. Every time a colony is marked, apparatus will register count with a bleep sound and counter advance.
  • Press <correct/reset> key once for removal of each count If unwanted counts are made.
  • Place first petridish on receiver plate to use averaging facility.
  • At end of the count, press the <save> key to store the count in the memory. This will indicated by three dashes on the display. Replace petridish with next and press <save>key to resume the count. Repeat until all dishes have been counted.
  • At the end of the run press the <average> key to display the average count. When average facility is active a red LED spot at the top left hand corner of the display will be visible.
  • Press & hold the <correct/reset> key until the display returns to zero when count is completed. This will clear the memory of saved counts.
  • Switch unit OFF at mains after all the counting is completed.
  • Maintain Colony Counter Log Book, Annexure-I for each operation.
Cleaning & Disinfection Procedure     
  • Remove plate from instrument for cleaning the receiver plate,
  • Make sure that instrument is switch off position.
  • Disconnect power plug.
  • Remove petridish from platform.
  • Clean outside of the equipment initially with dry cloth.
  • Disinfect the outer surfaces with 5% Dettol/Savlon solution.
  • Finally clean with Purified water.
  • Clean after each work.
Maintenance

Inform to supplier or Engineering Department for corrective action, If Colony counter shows any mechanical, electrical or any others problem.

Download Annexure Here

Annexure I: Colony Counter Logbook

Colony counter Operation and cleaning procedure Read More »

Biosafety Cabinet Operating Procedure

Biosafety Cabinet; Purpose

To establish the ideal operation of Bio-safety Cabinet to confirm that the air are free from any microorganisms & any particle in order to favor microbiological test.

Biosafety Cabinet; Scope

This SOP applies for operation of Bio-safety Cabinet, Model: AC2-4E1 in Microbiology Section at XX Pharmaceuticals Limited.

Definitions
  • BSC    : Bio-safety Cabinet
  • DOP   : Dioctyl Phthalate
  • HEPA : High Efficiency Particulate Air.
  • IPA     : Iso Propyl Alcohol.
  • PAO   : Poly alpha olefin.
Responsibilities

The roles and responsibility is as follows

Executive, Microbiology

Operation, cleaning & disinfection and performance checking of Bio-safety Cabinet

Manager, Microbiology
  • Ensure Operation, cleaning & disinfection, performance checking and application of sound technical information.
  • Review that SOP is technically informative.
Head of Quality Assurance

Take initiative to Approval of SOP

Procedure:
Instructions
  • Do not wipe HEPA filter side of BSC.
  • Do not turn on UV light without full cover of slash.
  • Move always gently during operation of BSC to minimize air turbulence.
  • Care should be taken that water do not enter into HEPA filter through working station of down flow.
Operating Procedure
  • Press UV light button to turn on the UV light.
  • Wait for 30 minutes.
  • Press light button to turn on.
  • Pull up front slash at 50% open position. Open position (%) will be indicated on the display.
  • If show alarm, adjust position of slash.
  • Press FAN button to start up and wait for 3 minutes.
  • After 3 minutes, fan will be automatically started and
  • Use 70% ethanol/IPA to wipe all the surfaces of workstation, except in front of HEPA filter.
  • Use 70% ethanol to wipe all materials (Glassware’s, containers and other articles) before bringing them inside the Bio-safety Cabinet.
  • Start the work.
  • Use 70% ethanol to wipe again entire platform after finishing work.
  • Press light button to turn off.
  • Pull down to cover front slash at 0% open position. Open position (%) will be indicated on the display.
  • Press UV light button to turn on the UV light
  • Wait for 30 minutes to disinfect the whole cabinet.
  • After 30 minutes, press UV light button to turn off.
  • Disconnect the power plug of the cabinet.
Performance Check
  • Check the performance of HEPA filter by monitoring the Particle count and Microbial count once in a year and prepare the report in Annexure-I & Annexure-II
  • Check efficiency of HEPA filter by DOP/PAO test once in six months and prepare the report in Annexure-I & Annexure-II
Maintenance
  • Inform to the supplier or Engineering Department for maintenance, if Bio-safety Cabinet shows any mechanical, electrical or any others fault.
  • After maintenance, check HEPA filter efficiency & monitor Particle Count and microbial count.

Biosafety Cabinet Operating Procedure Read More »

Microscope Operation and cleaning procedure

Microscope; Purpose

To establish the procedure for ideal operation & cleaning of Microscope for use in microbiological test.

Microscope; Scope

This SOP applies for operation, cleaning and of Microscope, Model: CX21-LED SET1, Olympus, Japan in Microbiology Section at XX Pharmaceuticals Limited.

Definitions/Abbreviations

N/A

Responsibilities

The roles and responsibility is as follows

Executive/ Sr. Executive, Microbiology

Operation, cleaning and performance checking of Microscope

Manager, Microbiology

Ensure Operation, cleaning & disinfection and performance checking.

Head of Quality Assurance

Take initiative to Approval of SOP

Procedure:

Instructions
  • Use 2.5% Dettol/Savlon solution for cleaning of objectives lens, eyepieces and condenser.
  • Do not use any concentrate alcohol or any others solution.
  • Use only immersion oil on slide.
  • Wipe properly objective lens to remove immersion oil at the end of use.
  • Do not disassemble the microscope without approval of Head of Microbiology Section.
Operation Procedure
  • Wipe entire platform with clean cloth.
  • Prepare specimen (stain, if necessary) on a glass slide & place it on stage properly under objective lens with aid of adjustment knob.
  • Put on switch for light source.
  • Rotating light intensity adjustment knob for increase or decrease brightness clockwise or anticlockwise.
  • Adjust objective lens (10x, 40x, 100x) according to requirement.
  • Use both coarse focus and then Fine focus for better visualization.
  • Focus an area on the specimen, which is clearly defined or not over crowded.
  • Do not move specimen holder directly by hand this will damage rotator mechanisms of the knob.
  • First focus specimen with 10x then with 45x, and then with 100x objective lens (if necessary).
  • After work is done wipe again lens & platform with another clean cloth, separately.
  • Cover the microscope at end of the work.
Cleaning & Disinfection Procedure        
  • Switch off Microscope & disconnect power plug.
  • Remove slide from stage.
  • Clean outside of chamber with dry cloth.
  • Use 2.5% Savlon/Dettol solution to Disinfect outer surfaces of Microscope
  • Clean Objective lens smoothly & Ocular lens with clean, soft, fiber free cloth before and after use.
  • Clean objective lens with cider wood oil if found any stain on lens.
Maintenance

If Microscope shows any mechanical, electrical or any others problem, inform to supplier or Engineering Department for corrective action.

Microscope Operation and cleaning procedure Read More »

Incubator Operation, Cleaning and Calibration Procedure

Incubator; Purpose

To operate, clean & calibrate incubator in order to support the bacterial growth in microbiological test.

Incubator; Scope

This SOP applies for operation, cleaning and calibration of Incubator, Model : INE500 & INE600 in Microbiology Section At  XX Pharmaceuticals Ltd.

Definitions/Abbreviation

[] CAL.1: Calibration Temperature 1

[] CAL.2: Calibration Temperature 2

[] CAL.3: Calibration Temperature 3

Responsibilities

The roles and responsibility is as follows

Executive/ Senior Executive, Microbiology
  • Follow the instructions of this procedure correctly.
Assistant Manager, Microbiology
  • Confirm that this procedure is kept up to date.
  • Confirm appropriate personnel from the section are trained on this procedure.
  • Confirm that SOP is technically sound and reflects the required working practices.
Head of Quality Assurance

Take initiative to Approval of this SOP

Procedure

Instructions
  • Do not wipe with damped cloth at on position.
  • Use only 70% IPA or Ethanol to wipe chamber with any disinfectants
  • Never overload the chamber with tested items.
  • Do not keep the items those may produce inflammation with air.
  • Keep all tested items to avoid the touch inner surface of the chamber.
  • Do not move the incubator at on position. Severe vibrations may cause serious damage of the temperature probes.
Operation Procedure
  • To the front of the instrument, Press push/turn control key to put on the main power switch. The incubator will start in normal mode with display of the timer, chamber temperature, alarm temperature (red color indication).
  • Turn the push/turn control key by holding down SET key, at the clockwise or anti clockwise for setting date, local time, operating temperature, and alarm temperature. After setting, SET key will be released the display briefly flashes the set point.
  • The display then changes to the actual current temperature & starts to the setting temperature. The temperature will be automatically augmented at setting temperature and display the setting temperature digitally.
  • Observe display temperature until its stable position.
  • Hold down the SET key (Approximately 3 Seconds) to select the operation mode, if require. The current operating mode will be flashed on the display. There are three operating mode in the incubator.
    1. Normal Operation
    2. Weekly Programmer
    3. Ramp time Programme Operation­­­
  • Select required programme & set as per operation manual.
  • Select fan speed to set air changes.
  • Turn the push/turn control at clockwise until the fan symbol flashing to move air slider opens & closes the air valve to control supply and discharge of air.
  • Check chamber temperature using by a calibrated digital thermometer, when setting Temperature reaches.
  • Keep required materials inside incubator.
  • Incubator will automatically control Temperature.
  • Instrument will automatically adjust the temperature. When the temperature exceed the setting temperature, “off” light will illuminate and if the temperature decrease the “on” light will illuminate.
Cleaning & Disinfection Procedure
  • Switch off incubator & disconnect power plug.
  • Remove all test flasks & others items from chamber of incubator.
  • Clean inside of chamber initially with dry cloth & wipe finally with 70% IPA wetted cloth.
  • Clean outside of chamber with dry cloth.
  • Disinfect all surfaces with 5% Savlon solution & dry outer surface of the incubator.
  • Reload all items into chamber when reach to dry chamber surface.
  • At the end of cleaning, connect the power plug and switch on the incubator.
  • Clean chamber once in a month.
  • Clean outer surface of the incubator every day.
Performance Check
  • Check chamber temperature daily once.
  • Record chamber temperature in Daily temperature Record, Annexure-I.
  • Temperature range ± 2.5° C from set temperature.
Calibration Procedure
  • Press and hold down SET key until normal mode light blinking.
  • Turn push/turn control key clock wise to reach SETUP light.
  • Select Calibration to rotate push/turn control key.
Use three calibration temperatures as below
  • 1 : Temperature calibration at low temperature
  • 2 : Temperature calibration at medium temperature
  • 3 : Temperature calibration at high temperature
  • Select required calibration temperature in SETUP key & set corresponding calibration correction to 0.00
  • Measure the deviation from selected calibration temperature under the steady conditions, using a reference instrument.
  • Set calibration correction in SETUP key. If measured reference temperature is too low, calibration correction setting is negative sign.
  • Adjust temperature if require from adjusting value of calibration temperature (CAL). Correction value should not more than ±10C.
  • Carry out check measurement using reference thermometer.
  • Carry out others two calibration temperatures in the same manner.
  • Calibrate incubator once in a year ± 15 days.
  • Record calibration in Calibration Record, as per Annexure-V of Engineering SOP
Maintenance
  • If Incubator shows any mechanical, electrical or any others problem, inform to supplier or Engineering Department for corrective action.
  • After corrective action, recalibrate incubator.

Download All Annexure Here:

Annexure I Daily Temperature Record of Instrument

Annexure II Incubator Operation Log Book

Incubator Operation, Cleaning and Calibration Procedure Read More »

Laminar Air Flow Operating Procedure & its SOP

Laminar Air Flow Operating Procedure; Purpose

To confirm that the air are free from any microorganisms and any particle in order to favor of microbiological test.

Laminar Air Flow Operating Procedure; Scope

This SOP applies for operation and cleaning of Laminar Air Flow, Model: AHC-4D1 in Microbiology Section at XX Pharmaceuticals Ltd.

Definitions/Abbreviations

[] DOP: Dioctyl Phthalate

[] HEPA: High Efficiency Particulate Air

[] LAFWS: Laminar Air Flow Work Station

[] LAF: Laminar Air Flow

[] PAO: Poly-alpha-olefin

Responsibilities:

The roles and responsibility is as follows

Executive/ Senior Executive, Microbiology

Operation, cleaning and disinfection and daily performance check.

Manager, Microbiology
  • Confirm Operation, cleaning and disinfection and performance checking.
  • Confirm that SOP is technically informative & application of sound knowledge.
  • Confirm that Laminar Air Flow is suitable for working.
Head of Quality Assurance

Take initiative to Approval of SOP

Procedure:

Instructions
  • Do not wipe HEPA filter side of LAFWS.
  • Do not move rapidly in a sweeping motion during operation of LAF to minimize air turbulence.
  • Do not use any disinfectant containing chlorine-based substances as this may be corrosive of the stainless steel.
  • Do not use Bunsen burner & aerosol generating instruments whenever possible as they interfere with airflow.
  • Do not turn on UV lamp without the front cover setting.
Operating Procedure:
  • Switch on the main power.
  • Set the front cover & make sure that the clean bench is fully closed & the interlock is working effectively.
  • Press UV/Exit button to turn on the UV lamp. UV can only be turned on when fan and light both are off.
  • Wait for around 60 minutes.
  • After 60 minutes, remove front cover from LAFWS.
  • Turn on Fan/Up button to start fan.
  • Press to turn on Light/Down to illuminate light.
  • To turn electrical socket of inner cabin, Press Socket/Set button
  • Use 70% Ethanol/IPA to wipe the work surface.
  • Before continuing the work, Leave LAF for 10 minutes
  • After 15 minutes, wipe all materials with 70% ethanol before bringing them inside the LAF Hood.
  • Start the work.
  • Work in cleaned bench in a slow & controlled manner.
  • Move hands in & out of the work zone opening slowly.
  • Use 70% ethanol to wipe again the entire platform after end of the work,
  • Press Fan/Up button to turn off the fan.
  • Press Light/Down Turns off the light.
  • Set front cover and press UV/Exit button to turn on the UV lamp to decontaminate the work bench.
  • Switch off the UV/Exit to turn off the UV lamp after 30 minutes.

Cleaning Procedure

Work surface and wall

Clean work surface & walls with appropriate 5% Dettol/ Savlon solution.

Exterior surface
  • Use a damp cloth to clean the exterior surface, predominantly on the front & top in order to remove dust that accumulated there.
  • Use fresh with Sterile Purified Water (which is sterilized at 1210C for 15 minutes or filtered by 0.2 µm) to eliminate any remaining of cleaning agent.
  • Use MEK (Methyl-Ethyl-Ketone) solution to eliminate stubborn stains or spots on the stainless steel surface. In such cases, wash the stainless steel immediately afterwards with clean water and liquid detergent. Then use polyurethane cloth or sponge for washing.
Microbiological Performance Check
  • Check performance of HEPA filter by monitoring Particle count & Microbial count before conducting sterility test.
  • For non-sterile preparation, check performance of HEPA filter by monitoring the particle count & microbial count in every six months.
HEPA Filter Integrity Test
  • Check efficiency of HEPA filter by DOP (Dioctyl Pthallate)/PAO(Poly Alpha Olefin) test once in  a year.
Maintenance
  • If LAF exhibits any mechanical, electrical or any others difficulty, notify to the supplier or Engineering Department for repairs.

Laminar Air Flow Operating Procedure & its SOP Read More »

Working Guideline in Microbiology Laboratory & its SOP

Working Guideline in Microbiology Laboratory; Purpose

To confirm that microbiological best laboratory practice and special precautions are maintained in Microbiology laboratory in order to prevent laboratory & personal contamination.

Working Guideline in Microbiology Laboratory; Scope

This SOP applies for maintaining microbiological best laboratory practices and special precautions in Microbiology Laboratory at XX Pharmaceuticals Limited.

Definitions/ Abbreviation

None

Responsibilities:

The roles and responsibility is as follows

 Executive/ Senior Executive, Microbiology

Maintain microbiological best laboratory practices & special precautions.

Manager, Microbiology

Ensure microbiological best laboratory practices, special precautions and application of sound technical information.

Head of Quality Assurance

Take initiative to Approval of SOP

Procedure:

Media Preparation and Quality Control

Working Guideline in Microbiology Laboratory; Media Preparation
  • Choose correct media or components in making media based on the use of accepted sources or references for formula.
  • Check Certificate of Analysis describing expiry date, storage conditions etc.
  • Read instructions on the label carefully before media selection and preparation.
  • Follow if any special instruction such as heating, additives & pH adjustment etc.
  • Use always purified water for media preparation.
  • Record accurate weight of media & make up volume with purified water.
  • Dissolve media thoroughly into water prior to dispensing & sterilization.
  • Avoid overheating or less heating media.
  • Sterilize the media as per label of the container.
Media Storage
  • Label media properly with batch or lot numbers, preparation & expiry dates.
  • Store media according to manufacturer’s instructions.
  • Store prepared media under validated conditions.
  • Do not store agar at or below 00 Because freezing could damage the gel structure.
  • Protect stored media from exposure to light & excessive temperature.
  • Before prolonged storage, place into a sealed package or container to retard moisture loss.
  • Re-melt agar media in a hot water bath or by using free flowing steam only once.
Quality Control Testing of Media:
  • Check pH & growth promotion to confirm media efficacy.
  • Perform limited growth promotion test for each lot, if media is sterilized using a validated method.
  • Do not use media if any parameters do not comply.
  • Pre-incubate & 100% inspection prior to use the media.
  • Maintain double-wrapped condition for those media used in critical environmental monitoring.
Maintenance of Microbiological Cultures:
  • Handle with care microbiological cultures due to their pathogenicity and toxicity.
  • Use as standard culture from international recognized organization such as American Type Culture Collection (ATCC), National Collection of Type Culture (NCTC) or any other manufacturer.
  • Select Standard culture as freeze dried lyophilized condition in vial or ampoules form or ready to use condition with Certificate of Analysis.
  • Ensure identification of culture prior to its use.
  • Use only permitted method for culture maintenance.
  • Maintain storage and sub-culture as per standard operating procedure for standard culture maintenance.
  • Be care to prevent extreme sub-culturing working control cultures that increase the risk of contamination.
  • Preserve all typical culture at 2 to 8
  • Inoculate frozen stock monthly or weekly.
  • Discard any unused portion to minimize risk of loss of viability & contamination of the stock.
Maintenance of Laboratory Equipment
  • Perform standard validation practices such as Installation Qualification, Operational Qualification and Performance Qualification for equipment.
  • Calibrate equipment periodically.
  • Check performance of all equipment’s on a routine basis.
  • Maintain always approved protocol for IQ, OQ & PQ of equipment’s.
  • Clean & disinfect all equipment’s as per standard operating procedure for that equipment.
Laboratory Operation
  • Isolate items between sterility testing room & microbial limit test and bio-assay room.
  • Do not interchange item between those area without sterilization.
  • Sanitize carefully both hands with appropriate sanitizer.
  • Before entrance into the test room, wear garments, mask and gloves as appropriate.
  • Always use sterile garments, gloves and mask into sterility testing area.
  • Aseptically handle the items into microbial limit test room.
  • Disinfect all items with 70% IPA or any others suitable sanitizer, before transfer the items into testing room. Open growth plate only into bio-assay room or microbial testing room.
  • Aseptically collect the sample.
  • Identify contaminants at least genus level.
  • Use specific sample area to preserve all samples.
  • Isolate all contaminated samples to reduce the false-positive results.
  • Follow SOP for disposal of used media to discard all contaminants.
  • Clean & disinfect all area according to SOP of cleaning and sanitizing Quality Assurance Department.
  • Lessen the movement into microbial testing room and bio-assay room.
  • After completion of sterility, exit from sterility testing room.
  • Wear another set of sterile dress, gloves, mask If require to re-enter into sterility test room.
  • Wash both hands with liquid soap or any skin cleanser solution, after completion of test and before exit from Laboratory, Finally disinfect both hands.
Documentation
  • Prepare documents in approved format.
  • Preserve documents into specific file up to defined period.
  • Review & update all standard operating procedure, specification & analytical Method within defined period.
  • Verify the data & calculation.
Maintenance of Laboratory Records
  • After completion of each work, prepare record in approved format
  • Follow approved SOP to reflect how the test is actually performed.
  • Keep calibration record after Perform calibration of any equipment’s
  • Preserve all records after approval.
  • Do not discard any approved record without permission and proper justification.
  • Forward test result of raw materials, in-process & finished products to the respected department.
  • Achieve and protect all laboratory record against catastrophic loss.

Spillage Management

Spills:
  • Report immediately to the reporting authority after spillages of culture.
  • Do not touch any spilled cultures & surrounding debris( e. g. glass , cotton or wool plugs) with exposed hands.
  • Wear disposable gloves & disinfect area by covering spill with several layers of paper towel/ cloth soaked in a suitable disinfectant.
  • Leave for it for 15-30 minutes.
  • Using paper towels, sweep spill debris into dustpan.
  • Transfer all disposable materials to a suitable container e.g. an roasting bag/autoclave for autoclaving and disposal.
  • Decontaminate dustpan either by autoclaving or by soaking (at least 24 hours) in hypochlorite solution.
Broken glass
  • Sweep carefully into a suitable container.
  • Dispose in a puncture proof container.
Splashes on clothing and skin
  • Soak in disinfectant contaminated cloth.
  • Treat to splash on skin as soon as possible.
  • Wash thoroughly with soap & finally with hot water.
  • Disinfect the skin if necessary.

Working Guideline in Microbiology Laboratory & its SOP Read More »

Validation of Moist Heat Sterilizer by its best method

Validation of Moist Heat Sterilizer; Purpose

To validate Moist Heat Sterilizer by Biological Indicator.

Validation of Moist Heat Sterilizer; Scope

This SOP applies for validation of Moist Heat Sterilizer in Sterile Processing area and Microbiology Laboratory at XX Pharmaceuticals Limited.

Definitions/Abbreviation

Validation

Validation is the process to establish documented evidence, which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications & quality attributes.

Biological Indicator

Biological Indicator is a defined preparation of viable spores made from Bacillus stearothermophillus & Bacillus subtilis & has a particular spore count per indicator of not less than 104 and not more than 109 spores which is used to monitor the efficacy of sterilization process.

  • BI: Biological Indicator
  • ATCC: American Type Culture Collection
  • NCTC: National Type Culture Collection
Responsibilities

The roles and responsibility is as follows

Executive/ Senior Executive, Microbiology

Preservation of Biological Indicator, perform Moist Heat Sterilizer validation and report preparation.

Manager, Microbiology

Ensure Moist Heat Sterilizer Validation, documentation and application of sound technical information.

Head of Quality Assurance

Take initiative to Approval of this SOP

Procedure

Instructions
  • Biological Indicator is usually non-pathogenic but all microorganisms are unscrupulous pathogen. So before handling it, wear protective items such as sterile wear sterile latex free gloves, laboratory coat & eye protection (if required).
  • Discard all items after autoclave.
  • At the end of work, leave all used items at designated containers safely.
  • Make sure that all personal ornaments, cell phone are left to prevent unauthorized contamination, before entrance into the test room.
Handling of Biological Indicator
  • Check expiry date of Biological Indicator (Bacillus stearothermophilus, ATCC-7953).
  • Discard it after autoclaving if expiry date is exceeded
  • Observe Certificate of Analysis of Biological Indicator.
  • Ensure that the paper strip is fully intact.
  • Preserve always BI at 250C or as per manufacturer instructions.
  • Do not preserve it at freezer.
Validation Frequency

Perform the validation once in six months interval.

Exposure of Indicator:
  • Carry out validation as per test schedule.
  • Map the chamber with most critical area for exposure of Biological Indicator.
  • Define location & label on each Biological Indicator.
  • Place spore strip of Biological Indicator of Bacillus stearothermophilus (ATCC 7953) at 8 points as per chamber mapping, table-1.
  • Complete sterilization cycle along with product to be sterilized or empty sterilizer.
Analysis of Indicator

After sterilization, Cut cover paper aseptically & transfer paper strip into separate test tube containing 9 ml of sterile Tryptone Soya Broth including a positive control & negative control.

 

Validation of Moist Heat Sterilizer

 

Incubation of Indicator:

Incubate all strips including positive & negative control at [50 to 55]0C for 7 days.

Interpretation of Result

Observe indicator strip after 7 days for growth. Turbidity of culture media indicates positive growth. Sterilizer is valid if the following criteria are met:

  • No growth found in exposed all indicator strip
  • No growth found in negative control indicator strip.
  • Growth found in positive control indicator strip.
Repeat validation if following result is found
  • Growth found in one or more than one exposed indicator strip
  • Growth found in negative control indicator strip.
  • No growth found in positive control strip.
The sterilizer is invalid if the following result are found
  • Growth found in one or more than one exposed indicator strip
  • No growth found in negative control indicator strip.
  • Growth found in positive control indicator strip.
Correction Action:
  • If growth found in anyone indicator strip in repeat test, inform test result to concerned department and Engineering Department for corrective action.
  • After corrective action, Engineering Department shall inform to Microbiology Lab. for the repeat test.
  • Microbiology Section shall perform the complete test.
Report Preparation

Report the validation in Moist Heat Sterilizer Validation Report, Annexure-I.

Download Annexure Here:

Annexure I Moist Heat Sterilizer Validation Report

Validation of Moist Heat Sterilizer by its best method Read More »

Validation of Dry Heat Sterilizer; perform it best way

Validation of Dry Heat Sterilizer; Purpose

To validate Dry Heat Sterilizer by Biological Indicator & endotoxin Indicator.

Validation of Dry Heat Sterilizer; Scope

This SOP applies for validation of Dry Heat Sterilizer in Sterile Processing area and Microbiology Laboratory at XX Pharmaceuticals Limited.

Definitions/Abbreviation
Validation

Validation is the process to establish documented evidence, which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications & quality attributes.

Biological Indicator

Biological Indicator is a defined preparation of viable spores made from Bacillus stearothermophillus & Bacillus subtilis & has a particular spore count per indicator of not less than 104 and not more than 109 spores which is used to monitor the efficacy of sterilization process.

Endotoxin Indicator

Endotoxin Indicator are designed for monitoring depyrogenation process or validation or which may be measured by comparing the levels of endotoxin before and after a depyrogenation cycle using LAL reagent . USP[United State Pharmacopoeia]  suggests that a depyrogenation cycle should be reduce the endotoxin  by at least 1000 fold ( 3- log reduction ) in endotoxic activity as measured by LAL method.

Endotoxin

It is the component of cell wall of certain bacteria which type of bacteria is known as gram negative bacteria. Endotoxin induce strong immune response and enhance release of cytokine.

[] ATCC: American Type Culture Collection

[] BI: Biological Indicator

[] CSE: Control Endotoxin Standard

[] EI: Endotoxin Indicator

[] λ: Lambda(Lysate Sensitivity)

[] LAL: Limulus Amebocyte Lysate

Responsibilities

The roles and responsibility is as follows

Executive/ Sr. Executive, Microbiology

Preservation of all Indicator, perform Dry Heat Sterilizer validation & report preparation.

Manager, Microbiology

Ensure Sterilizer Validation, documentation and application of sound technical information.

Head of Quality Assurance

Take initiative to approval of this SOP

Procedure:

Instructions
  • Biological Indicator is usually non-pathogenic but all microorganisms are unscrupulous pathogen. So before handling it, wear protective items such as sterile wear sterile latex free gloves, laboratory coat & eye protection (if required).
  • CSE[Control Standard Endotoxin] is pyrogenic in humans. Care should be exercised when handling to avoid ingesting it.
  • Use caution if handling hot vials. Wear gloves or wait until vials are cool.
  • Before transferring BI[Biological Indicator] from Microbiology Laboratory, disinfect whole surface of all apparatus with the help of 70% IPA or any others disinfectants.
  • Leave it at designated containers safely.
  • Ensure that waste container is tightly capped until autoclaving.
Handling of Biological Indicator & Endotoxin Indicator :
  • Use BI[Biological Indicator] for sterilization cycle validation & EI[Endotoxin Indicator] for Depyrogenation cycle validation.
  • Read insert package carefully for instruction of use.
  • Check expiry date of Biological Indicator (Bacillus subtilis, ATCC-9372) and Endotoxin Indicator.
  • Discard it after autoclaving if expiry date is exceeded.
  • Observe Certificate of Analysis of all indicators.
  • Ensure BI[Biological Indicator] paper strip & EI [Endotoxin Indicator] vial is intact.
  • Preserve always BI at 250C and at [2 to 8]0C for EI.
  • Do not preserve it at the freezer.
Culture Media Sterilization :
  • Prepare required amount of CSDM [Casein Soyabean Digest Medium] for the test & distribute [15 to 20] ml of medium in different test tubes.
  • Sterilize media at 1210C for 15 minutes.
  • Preserve those at [2 to 8]0C for use.
Validation Frequency
  • Perform the validation once in six months.
Exposure Condition:
  • Carry out validation as per test schedule.
  • Map chamber with most critical area for exposure of BI[Biological indicator] or EI[Endotoxin Indicator].
  • Define location & label each BI or EI.
  • Place EI at 4 points & BI at 12 points as per chamber mapping, mentioned on Table-1.
  • Complete sterilization cycle along with product or empty sterilizer.
  • After sterilization, transfer all indicators to Microbiology Laboratory.
BI[Biological Indicator] Assay
  • Perform whole analysis under Laminar Air Flow workstation.
  • Aseptically open envelopes of BI[Biological Indicator] test strips.
  • Place each test strips including negative control and positive control strips in individual tubes containing [15 to 20]ml of TSB.
  • Identify all tubes.
Incubation of Biological Indicator
  • Incubate the BI strips at [300 to 35]0C for 7 days.
Interpretation of Result

Observe BI[Biological Indicator] tube daily for growth. Growth should occur in positive control tube within 48 hours. The turbidity indicates positive growth of tubes. Sterilizer is valid if following criteria are met:

  • No growth found in exposed all tubes.
  • No growth found in negative control tube.
  • Growth found in positive control tube.
Repeat validation if following result is found :
  • Growth found in one or more than one exposed tube.
  • Growth found in negative control tube.
Sterilizer is invalid if following result are found
  • Growth found in one or more than one exposed tube.
  • No growth found in negative control tube.
  • Growth found in positive control tube.
EI Assay Procedure of LAL Test(Gel Clot Method) :
  • Use the LAL reagent sensitivity 0.125 EU/ml for this assay.
  • Reconstitute each EI vial with 1.0 ml LAL water including Positive control & vortex at least five minutes and then dilute 1:8 by using LAL water at least duplicate.
  • Make a control series (2 λ, λ, λ/2, λ/4) if a new lot of Endotoxin indicator or LAL reagent is used. Otherwise test at λ (Lysate sensitivity) only.
  • Carry out LAL test for exposure vials, positive control and negative control as per Standard Operating Procedure for Bacterial Endotoxin Test.
Incubation of Indicator
  • Incubate all LAL test tubes including positive & negative control at [37±1]0C for [60±1] minutes.

Validation of Dry Heat Sterilizer

 

Interpretation of Result
  • A more exact calculation of endotoxin reduction is made by finding the end-point of the positive control, by ten-fold & then two fold dilution, & subtracting the logarithms of the exposed vial from the logarithms of the positive control.

Use the logarithm of lamda for the endotoxin concentration in exposed vials when there are negative LAL test results for the undiluted solutions.

The sterilizer is valid if the following criteria are met
  • No clot formed in all exposed tube
  • No clot formed in negative control tube
  • Clot formed in positive control tube
Repeat validation if the following result is found
  • Clot formed in one or more than one exposed tube
  • Clot formed in negative control tube
  • Not clot formed in positive control tube
The sterilizer is invalid if the following result is found
  • Clot formed in one or more than exposed tube
  • No clot formed in negative control tube
  • Clot formed in positive control tube
Corrective Action:
  • If endotoxin found in anyone exposed vial in the repeat test, inform the test result to concerned department & Engineering Department for corrective action.
  • After corrective action, Engineering Department or concerned department shall inform to Microbiology Lab. to perform the validation again.
  • Microbiology Section shall perform the complete test.
Report Preparation

Report the validation in Dry Heat Sterilizer Validation Report by Biological Indicator, Annexure-I and Dry Heat Sterilizer Validation Report by Endotoxin Indicator, Annexure-I

Download All Annexure Here:

Annexure I:  Dry Heat Sterilizer Validation Report by Endotoxin Indicator

Annexure II: Dry  Heat Sterilizer Validation Report by Biological Indicator

Validation of Dry Heat Sterilizer; perform it best way Read More »

Micropipette; Operation, Cleaning and Calibration Procedure

Micropipette; Purpose

To initiate that the procedure is suitable for ideal operation, cleaning and calibration of Micropipette for use in microbiology test.

Scope

This SOP applies for Operation, Cleaning & Calibration of Micropipette, Model: 8-105-00-9 & 8-106-00-9 in Microbiology Section at XX Pharmaceuticals Limited.

Definitions/Abbreviations

N/A

Responsibilities

The roles and responsibility is as follows

Executive/ Senior Executive, Microbiology

Operation, Cleaning and Calibration of Micropipette.

Manager, Microbiology
  • Ensure Operation, Cleaning, Calibration and application of sound technical information.
  • Review that SOP is technically informative.
Head of Quality Assurance

Take initiative to Approval of SOP

Procedure:

Instructions
  • Keep Micropipette always at vertical position on the respective stand.
  • Never sink Micropipette into water.
  • Never reset or adjust the volume.
  • Care should be taken during pipetting that solutions do not enter into Micropipette.
  • Do not try to volume highly viscous solution by this device.
  • Do not use hot solution in this device.
Operation Procedure
  • Check is calibration status of Micropipette. If Micropipette is not calibrated, calibrate it before use.
  • Set desired volume by turning red colored setting screw button at clock wise for increasing and anticlockwise for decreasing the volume.
  • Set micropipette tips on bottom side in tight condition.
  • After setting desired volume, observe display digit.
  • Draw desired volume of solution by pressing red colored setting screw in single punch.
  • Rinse tips least three times with solution at first time.
  • Deliver total volume by pressing same button at double punch.
  • Draw total volume of the solution.
  • Press setting screw for delivery the solution.
  • After use, always keep it on the stand at vertical position.
Cleaning Procedure
  • Clean outer surface with dry cloth.
  • Use 70% IPA solution to disinfect outer surfaces except display of Micropipette.
  • Clean Micropipette before & after use.
Calibration Procedure
  • Set Micropipette reading as 100 µL for Model: 8-105-00-9 & 500 µL for Model: 8-106-00-9.
  • Set tips with Micropipette properly.
  • Take distilled water of temperature at 250C±10C into a beaker.
  • Weigh & tare another 100 ml beaker.
  • Draw 100 µL or 500 µL of distilled water by Micropipette & deliver it into tarred beaker.
  • Record weight of distilled water.
  • Repeat same procedure up to nine times.
  • Calculate the accuracy(% of error) & Precision(% CV) as below :
  • Accuracy (% error) = Mean Value – Reference value/Reference value x 100
  • Precision (% CV) = Standard deviation/mean x 100.
  • Record the result in Micropipette Calibration Record, Annexure-I.
  • Calibration Frequency: Perform the calibration once in a year.
Maintenance

If Micropipette shows any error or any mechanical fault, inform to the supplier or Engineering Department for maintenance, after repairing or maintenance, recalibrate it before use.

Download Annexure Here:

Annexure I Micropipette Calibration Record

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Antimicrobial preservative effectiveness test & its SOP

Antimicrobial preservative effectiveness test; Purpose

Antimicrobial preservative effectiveness test; To confirm that the concentration of Antimicrobial Preservatives used in different drug preparations are able to kill or destroy or inhibit or prevent or terminate the growth of microorganisms and thus make the product stable throughout its declared shelf life.

Antimicrobial preservative effectiveness test; Scope

This SOP is applicable for Oral liquids tests at Microbiology Laboratory in XX Pharmaceuticals Ltd.

Definition/Abbreviation:  
Preservative:

Antimicrobial preservatives are the substances added to different dosage forms or products to protect or defend them from microbial growth or from different microorganisms that are introduced unintentionally during or succeeding in the manufacturing process.

[] ATCC: American Type Culture Collection

[] SDA: Sabouraud Dextrose Agar

[] TSA: Tryptone Soya Agar

Responsibilities:

The roles and responsibilities are as follows:

Lab Attendant

Sample collection

Executive/ Sr. Executive, Microbiology

Sample collection, analysis of preservative test & respective test report preparation.

Manager, QC/Microbiology
  • Ensure sampling, analysis, documentation & application of sound technical information.
  • Review of this SOP and confirm that the whole procedure is technically sound.
Head of Quality Assurance
  • Take initiative to Approval of this SOP.
  • To ensure the overall implementation of this SOP

Procedure:

Instructions
  • Use Bio-safety Cabinet to Perform tests of Antimicrobial preservative effectiveness of products.
  • Before preparation of media and conduct antimicrobial preservative effectiveness test, Wear a mask, Hand gloves and headgear Bring the media to the boil to dissolve completely before autoclave.
  • Mix well before pouring the substances.
  • Cool the broth media at room temperature (250C) and the agar media at 500C & for use as per the requirement of the test.
Media & Biochemical Preparation

As per Media preparation for Media, preparation SOP prepare the same.

Inoculum Preparation:
  • Remove the vial of pellets from refrigerated storage & allow equilibrating to the room condition.
  • Warm hydrating & diluting fluids to [34 to 38]0C, before use.
  • To achieve a concentration of about 108 cfu per ml, transfer pellets to hydrating fluid.
  • Immediately place the microbial suspension into a [34 to 38]0C incubator for 30 minutes
  • To assure complete hydration, immediately following incubation, vortex the hydrated material to achieve a homogenous suspension.
Inoculation of Microbial Suspension to Product
  • To give inoculums of 105 to 106 microorganisms per ml of product and mix well, inoculate the product to be examined, each with a suspension of the test organisms.
  • The volume of the suspension of inoculums does not exceed 1 percent of the volume of the product.
  • Maintain the inoculated product at the temperature range from [20 to 25]0C and protected it from light.
  • According to the type of the product, Remove 1 ml sample from each container at suitable intervals & determine the number of viable microorganisms using the Pour plate method.
Suitability of counting method for non-sterile products

As per suitability of counting method for suitability of Microbial count, method SOP perform the same.

Test Sample Preparation
  • Aseptically accurately measured 1 ml sample to be transferred from each inoculated product container to a market sterile capped dilution tube containing 9 ml of sample diluent & mix well. The ratio of this dilution is 1:10.
  • Aseptically accurately measured 1 ml sample to be transferred from 1:10 dilution to a second dilution tube containing 9 ml of sterile diluent and mix well. This is the ratio of this dilution is 1:100.
  • Continue this dilution up to 10-5 or as essential levels.
Plating and incubation:
  • Take two sterile petri plates then Take 1 ml quantity sample from each dilution.
  • Maintain the temperature not more than 450C, then For Bacterial count pour 15 to 20 ml of sterile TSA medium into each plate being at and mix well.
  • Maintain the temperature not more than 450C, For Fungal count, pour 15 to 20 ml of sterile SDA medium into each plate being and mix well.
  • Pour two plates with TSA & SDA medium each with 1 ml diluents as the negative control.
  • After solidification incubate them at [20 to 25]0C for 5 to 7 days for the fungal count and [30 to 35]0C for 3 to 5 days for the bacterial count.
Acceptance Criteria
  • For Oral Liquid & Other than Antacids
  • For Bacteria (S. aureus, E.coli & P. aeruginosa)
  • Not less than 1.0 log reduction from the initial count at 14 days.
  • No increase from the 14 days counts at 28 days.
For Fungi (C. albicans, A. brasiliensis)
  • No escalation from the initial calculated count at 14 and 28 days.
For Oral Liquid Antacids Preparation
  • For Bacteria (E.coli, P. aeruginosa, S. aureus)
  • No upsurge from the initial calculated count at 14 and 28 days.
For Fungi (C. albicans, A. brasiliensis)
  • No increase from the initial calculated count at 14 and 28 days.
[Reference of acceptance criteria: USP 41]

Download All Annexure Here:

Annexure I: Preservative Efficacy Test Report Oral Liquid Preparation
Annexure II: Preservative Efficacy Test Report Oral Liquid Antacids Preparation

Antimicrobial preservative effectiveness test & its SOP Read More »

Validation of Laminar Air Flow and Its SOP

Validation of Laminar Air Flow; Purpose

To validate Laminar Air Flow in order to support of processing area and Microbiology Test.

Validation of Laminar Air Flow; Scope

This SOP applies for validation of Laminar Air Flow used in Processing area and Microbiology Section XX Pharmaceuticals Ltd.

Definitions/Abbreviation :

Validation: Validation is the established documented evidence, which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications & quality attributes.

DOP Test: Dioctyl Pthalate is a combustible non-toxic colorless oily liquid with slight odor. This chemical is used in HEPA filter integrity test at vaporized condition by DOP Test Meter.

[] HEPA : High Efficiency Particulate Air

[] CSDA : Casein Soyabean Digest Agar

[] SDA    : Sabouraud Dextrose Agar

[] LAF    : Laminar Air Flow

 Responsibilities

The roles and responsibility is as follows

Executive/ Senior Executive, Microbiology

Perform Microbiology Air monitoring of Laminar Air Flow & report preparation.

Executive/ Senior Executive, Engineering

Perform Air Velocity Test, DOP test and report preparation.

Microbiology/ Assistant Manager, Engineering

Ensure Laminar Air Flow Validation, documentation and application of sound technical information.

Head of Quality Assurance

Take initiative to Approval of SOP

Procedure:

Instructions
  • Wear protective items such as sterile latex free gloves, laboratory coat and eye protection (if required).
  • Disinfect whole surface of all apparatus with the help of 70% IPA or any others disinfectants before transferring into Laminar Air Flow.
  • Make sure that all personal ornaments, cell phone are left to prevent unauthorized contamination, before working under Laminar Air Flow.
Microbiological Monitoring
  • Start Laminar Air flow at least before 30 minutes of validation.
  • Select sampling point as mentioned on Table-1.
  • Expose sterile CSDA and SDA plate for 30 minutes under LAFWS at different location as per sampling points.
  • After sampling, cover all plates with the glass lids.
  • Incubate all CSDA plate at (30 to 35)0C for 72 hours and SDA plate at (22 to 25)0C for 5 days including positive control & negative control plate.
  • After incubation, count the CFU per plate.
  • Report in Laminar Air Flow Validation Report, Annexure-I.
  • Perform this test yearly.
 Detection of Air Velocity
  • Disinfect outer surface of Anemometer with the help of 70% IPA before transferring into LAF.
  • Measure distance 6” from HEPA.
  • Take air flow reading of HEPA of LAF by moving smoker from left to right & top to down.
  • Check that any deviation of reading found for air velocity. If found mark that point.
  • Report Air Velocity & Filter Integrity Test Report of Laminar Air Flow, Annexure-II.

Filter Integrity Test

  • Set DOP Test Meter with DOP test port of LAF.
  • Run machine as per SOP of DOP Test Meter.
  • Take air by smoker of DOP Test & record the reading.
  • Check any deviation of reading.
  • Report Air Velocity & Filter Integrity Test Report of Laminar Air Flow, Annexure-II.
Validation Frequency

Perform LAF Validation once in a year.

Validation of Laminar Air Flow

 

Corrective Action:

[] If growth obvers in anyone plate, inform the test result to concerned department & Engineering Department for corrective action.

[] If the test result found out of specification in Air Velocity Test or Filter Integrity Test, Engineering department shall take necessary action.

[] Microbiology Section and Engineering Department shall perform the complete test.

Download All Annexure Here:

Annexure I Air Velocity & Filter Integrity Test Report of Laminar Air Flow Biosafety Cabinet
Annexure II Laminar Air Flow Bio-safety Cabinet Validation Report

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Microbial Examination of Empty Bottle, Cap & Stopper

Microbial Examination of Empty Bottle, Cap & Stopper; Purpose

To confirm that the bacterial & fungal count & specified microorganisms into empty bottle during filling are within In-house specification.

Scope

This SOP is applicable for microbiological test of empty bottle during filling in Microbiology Section at XX Pharmaceuticals Ltd.

Definitions/Abbreviation

[] CSDA: Casein Soyabean Digest Agar

[] CSDM: Casein Soyabean Digest Medium

[] SDA  :  Sabouraud Dextrose Agar

[] TAMC: Total Aerobic Microbial Count

[] TYMC: Total Yeast & Mould Count

Responsibilities

The roles and responsibility is as follows

Executive, Microbiology

Sample collection, analysis and documentation.

Manager, Microbiology/Quality Control

Ensure analysis of empty bottles, documentation and application of sound technical information.

Head of Quality Assurance

Take initiative to Approval of this SOP

Procedure

Instructions
  • When enter into the test area, wear sterile latex free gloves, mask, laboratory coat & eye protection (if required).
  • Make sure that all personal ornaments cell phone are left to prevent unauthorized contamination, before entrance into test area.
  • Move always gently and never move vigorously into the test area.

General Requirements for the test

Glass Apparatus
  • Sterilized 90 mm Glass Petridish
  • Screw capped Conical Flask 100 ml
  • Screw Capped Test Tube
  • Volumetric Flask 1000 ml
  • Volumetric Flask 500 ml
  • Pipette 2 ml, 10 ml
Media and Reagents
  • Casein Soyabean Digest Agar(CSDA)
  • Casein Soyabean Digest Medium(CSDM)
  • Mac-Conkey Broth
  • MacConkey Agar
  • Neutralized Peptone
  • Sabouraud Dextrose Agar
Others Requirements
  • Surgical Gloves
  • Surgical Cotton
  • 70% IPA or ethanol

Enumeration Method(TAMC & TYMC)

This test quantifies the enumeration of mesophillic bacteria & fungi that may grow under aerobic conditions.

Test Conditions
  • Disinfectant both hands, bottles surface, Laminar Air Flow workstation with 70% IPA or 70% ethanol before starting test.
  • Carry out the test under Laminar Air Flow to avoid contamination.
Culture Media Preparation
  • Prepare different culture media as per requirement.
  • Weigh accurate amount mentioned in the manufacturer label into appropriate flask.
  • Bring to boil completely to dissolve media.
  • Sterilize at 1210C for 15 minutes or as per manufacturer label.
  • Store prepared culture media in air tight flask at 2 to 80
Stock Buffer Solution
  • Take 34 g of Potassium Dihydrogen Phosphate[KH2PO4] in a 1000 ml volumetric flask.
  • Dissolve in 500 ml of Purified Water, adjust to pH 7.2 ± 0.2 & dilute to 1000ml with Purified Water.
  • Dispense 90 ml into each screw capped flask.
  • Sterilize at 1210C for 15 minutes.
  • Store prepared buffer at 2 to 80C for a validated period.
Glassware Cleaning & Sterilization
  • Clean all glassware by 1% detergent initially & then rinse with sufficient tap water.
  • Rinse finally with sufficient Purified Water to remove residual content of detergent.
  • Sterilize all glassware at 2000C for 1 hour.
Sample Size
  • Collect 5 empty sealed bottles from each batch during filling of the products at three stages of Starting, Middle and Ending of operation.

Test Method

  • Carry out anyone from the following mentioned method
Pour plate method
  • Transfer all bottles under Laminar Air Flow.
  • Deseal the cap of all bottles.
  • Add 10 ml sterile meat peptone or phosphate buffer pH 7.0 ± 0.2.
  • Cap the bottles & shake well to mix properly.
  • Mark all petridish as product name, batch number, plate name (CSDA/ SDA) and bottle number & test date.
  • Take 1 ml of rinsing solution from each bottle & pour into two 90 mm sterilized petridish.
  • Add 15-20 ml CSDA into one plate & add 1 ml SDA into another plate.
  • Maintain same manner for the rest 4 bottles.
  • Mix sample with the media by tilting & rotating the plate.
  • Allow to solidify all plates & invert after solidification.
  • Incubate CSDA at 30 to 350C for 3 to 5 days & at 20 to 250C for 5 to 7 days.
  • After incubation, calculate number of cfu per bottle.
Negative Control

Use the diluents as sample in place of test preparations and follow the steps mentioned steps.

Membrane Filtration Method
  • Prepare sample as per Pour Plate Method
  • Filter whole rinsing solution of all bottles individually through 0.45 µm and transfer the filter paper to the surface of CSDA slant for bacterial count and SDA slant for yeast & mold count.
  • Invert plates & incubate all CSDA plates at 30 to 350C for 3 to 5 days & SDA plates at 20 to 250C for 5 to 7 days.
  • After incubation, count the colony of each plate.
  • Calculate number of cfu per bottle.
Negative Control

Use the diluents as sample in place of test preparations and follow the steps mentioned steps.

Surface spread Method
  • Spread not less than 0.1 ml of rinsing solution on surface of two CSDA & two SDA Plate.
  • Dry all plates under Laminar Air Flow work station.
  • Incubate CSDA at (30 to 35)0C for 3 to 5 days & at (20 to 25)0C for (5 to 7) days.
  • After incubation, calculate number of cfu per bottle.
Negative Control

Use the diluents as sample in place of test preparations and follow the steps mentioned steps.

Interpretation of the results
  • The bottles are passed if the observed count is less than specified count.
  • The product is failed if the observed count is greater than specified count of that product.
Test Control
  • Negative control must be negative growth. If found growth in negative control, the test is invalid.

Test for Specified Microorganisms

Suitability of Test Method
  • Add each test strain separately not more than 100 cfu at the time of bottle test mixing with culture media as per standard operating procedure of Suitability of Microbial Count Method.
  • The test is suitable if growth found the specific microorganisms. The test is not suitable if no growth found the specific microorganisms. In that case, add any neutralizer or increase dilution for removal any inhibition of product.
 Test for E. coli
  • Add 10 ml of test sample to 90 ml of CSDM. Incubate at (30 to 35)0C for 18 to 24 hours.
  • Shake the container and transfer 1 ml of CSDM to 100 ml of MacConkey Broth.
  • Incubate at (42 to 44)0C for 24 hours.
  • Sub culture on MacConkey Agar plate from MacConkey broth.
  • Incubate at (30 to 35)0C for (18 to 72) hours.
  • The product complies with the test for E. coli if no red colonies are present with precipitated zone & the biochemical tests are negative.
Test Report Preparation

Microbial Examination Report of  Cap & Stopper, Annexure-I.

Microbial Examination Report of Empty Bottle, Annexure-II.

Download All Annexure Here

 Microbial Examination Report of Cap & Stopper Annexure-I.
 Microbial Examination Report of Empty Bottle Annexure-II.

Microbial Examination of Empty Bottle, Cap & Stopper Read More »

Microbiology Analysis of Surface Swab and its SOP

Microbiology Analysis of Surface Swab; Purpose:

To confirm that the processing area & processed equipment’s are free from any intolerable microorganisms & total aerobic count are within specification.

 Microbiology Analysis of Surface Swab; Scope:

This SOP applies to detect or count of bacteria and Yeast/Mold in Non-sterile Processing, Sterile Processing Area & Testing area of Microbiology laboratory at XX Pharmaceuticals Ltd.

 Definition:  

Swab test & Finger Printing are to check with a view to take timely corrective measures for maintaining a favorable manufacturing environment, minimizing the risk of contamination of the products.

Responsibilities:

The roles and responsibility is as follows

Executive/ Senior Executive, Microbiology

Sample collection, analysis of swab and document preparation

Manager, Microbiology

Confirm sampling, analysis, documentation & application of updated technical information.

Head of Quality Assurance

Take initiative to Approval of this SOP

Procedure:

Instructions
  • Disinfect with the help of 70% IPA/Ethanol the whole outer surface of machine & all apparatus.
  • Wear gloves, mask & sterilized garments before entrance into aseptic area.
  • Minimize the movement into aseptic area or others sampling area.
Swab Test of Garments/Floor/Wall/Equipment
Sterilization of Swab Kits and Culture Media
  • Prepare swab kits with cotton bud as per requirement.
  • Roll tightly a small amount of cotton of surgical grade at one end of the glass rod.
  • Place cotton bud in a narrow test tube.
  • Plug end of test tube with the help of non-absorbent cotton.
  • Prepare CSDA [Casein Soybean Digest Agar], CSDB [Casein Soybean Digest Broth] according to the requirement of the test. Distribute 50ml of CSDB in each conical flask.
  • Sterilize media & test tubes containing cotton bud & Template steel plate at 1210C & 15lbs pressure for 15 minutes in an autoclave.
Swab Collection
  • Select a steel template of 5 x 5 cm. size.
  • Sterilize steel template by alcohol flaming before the test
  • Wipe cotton bud slowly & firmly in interior direction of steel template on the surface, selected for test.
  • Rotate cotton bud against direction of the overall wiping movement.
  • Repeat process for three times.
Collected Sample Preservation
  • Perform test within 30 minutes after collection of sample.
  • Preserve sample at 2 to 80C at not more than 12 hours if test is not performed within 30 minutes.
 Test Method
  • Place swab immediately in a bottle containing 50ml of CSDB.
  • Pull cotton free in the medium.
  • Shake bottle containing swab for sometime in a shaker.
  • Pour 1ml of diluent into sterile petridishes with aid of a sterile pipette.
  • Add 20 to 25ml of Tryptone Soy Agar at about 45 to 500C to the plate.
  • Mix medium with sample by rotating petridish.
  • Allow medium to solidify & then keep plate for incubation at 370C for 48 hours.
  • After incubation period count number of colonies either by colony counter or visual inspection.
  • Carry out the test in every week.
Interpretation of Test Result
  • Report swab test if test result found in Swab Test Report, Annexure-I.
  • If test result found out of specification, repeat the test.
  • Recollect swab sample from same area or same person.
  • Carry whole test as previously performed
  • If test result found within specification as per table-1, report the test result in Annexure-I.
Personnel Finger Printing :
Culture Media Preparation and Sterilization
  • Prepare CSDA [Casein Soybean Digest Agar] for the test according to the requirement of the test following the instructions of the respective manufacturer.
  • Autoclave medium at 1210C & 15lbs pressure for 15 minutes.
  • Pour approximately (20 to 25) ml of medium in each plate after autoclaving.
  • Allow medium to solidify & then keep in refrigerator until use.
  • Dry surface of agar media.
  • Do not use prepared plate after 72 hours.
  • Take medium aseptically to respective department.
Collection of Finger Print
  • Take finger print of both the hands, of each person working in the aseptic area in the separate plate.
  • Mark each plate with person’s name, area /room no., hand (right/left) and date.
  • Aseptically bring plates back to microbiology laboratory
  • Incubate plates at (30 to 35)0C for 48 hours.
  • After incubation count number of colony forming unit formed on each plate either by visual examination or by colony counter.
  • Carry out test every week for sterile process operator & once in a month for Non-sterile process operator.
 Interpretation of Test Result
  • Report swab test if test result found in Swab Test Report, Annexure-I.
  • If test result found out of specification, repeat the test.
  • Recollect swab sample from same area or same person.
  • Carry whole test as previously performed
  • If test result found within specification as per table-1, report the test result in Annexure-I.
Out of Specification

If test result found out of specification, send test report to concerned Sectional Head for corrective action.

After corrective action, repeat the test for specific area or person.

Download the All Annexure Here

Annexure 1 Swab (Microbial) Test Report
Annexure II Finger Print Test Report

Microbiology Analysis of Surface Swab and its SOP Read More »

Maintain and preserve of standard culture and its SOP

Maintain and preserve of standard culture; Purpose

To maintain & preserve the standard culture in order to use in specific microbiology test.

Maintain and preserve of standard culture;Scope

This SOP applies to preserve & maintain stock standard culture in Microbiology Laboratory of at XX Pharmaceuticals Ltd.

Definitions

Standard Culture

Standard culture is a specific microorganism of a specific strain that is recognized by BP/USP/Eur. Ph.  and certified by  ATCC/NCTC or any other standard culture bank. That culture is used in the different microbiological test such as Growth Promotion Test, Biological Assay of Antibiotics, Sterilizer Validation, Antimicrobial Preservative Effectiveness Test, Microbial Count suitability Test & Sterility Test Validation.

  • ATCC: American Type Culture Collection
  • NCTC: National Type Culture Collection
Responsibilities
Executive/ Senior Executive, Microbiology
  • Preparation of Culture Media, sub-culture, preservation and record keeping.
  • Follow the instructions of this procedure correctly.
Manager, Microbiology
  • Ensure that this procedure is kept up to date.
  • Ensure culture maintenance activities & proper documentation
  • Ensure appropriate personnel from the section are trained on this procedure.
  • Confirm that SOP is technically sound & reflects the required working practices.
Head of Quality Assurance

Take initiative to approval of this SOP

Procedure:

Instructions
  • Standard microorganisms are usually non-pathogenic but those are unscrupulous pathogen. So before handling it, wear protective items such as sterile latex free gloves, laboratory coat and eye protection (if necessary).
  • Move always gently. Don’t move vigorously into the test area.
  • Disinfect the whole surface with the help of 70% IPA or any others suitable disinfectants. After completion of sub-culture or transfer of pellets.
  • Take away all used items those are directly contacted with standard micro-organisms and Leave it at designated containers safely.
  • Confirm the waste container is tightly capped until autoclaving.
  • Never touch the apparatus directly in open hands those are used.
  • Make sure that all personal ornaments, cell phone are left before entrance into the test room, to prevent unwanted contamination.
Sterilization of Apparatus & Glassware:
  • Sterilize all glassware plus Latin Square Plate and others heat stable apparatus at 2000C for 60 minutes in hot air oven using a validated process.
  • Use the glassware when the temperature reduce to 400
Preparation of Culture Media:
  • Select media & diluents as per instruction of BP or USP.
  • Prepare required amount of Culture media of CSDA [Casein Soybean Digest Agar] & CSDB [Casein Soybean Digest Broth] and SDA [Sabouraud Dextrose Agar] as per indication by manufacturer instructions.
  • Bring to boil to dissolve it completely.
  • Distribute 10 ml of the media into each screw capped test tube.
  • Sterilize at 1210C for 15 minutes.
  • Cool media approximately to (45 to 50)0
  • Allow to solidify agar media to prepare slant.
  • Transfer broth media flasks into the test room.
  • Dry surface of agar slant keeping into Laminar Air flow or Bio-safety Cabinet.
  • Incubate sterilized CSDA [Casein Soyabean Digest Agar]/broth at (30 to 35)0C for 48 hours and SDA [Sabauroud Dextrose Agar] for 5 days at (22 to 25)0C for checking sterility of the media.
  • After incubation observe each test tube for growth. If no growth found, the media is suitable for use.
  • Store media at (2 to 8)0C into refrigerator until it use.
Preparation of Standard Microorganism:
Test Conditions

[] Disinfectant the surface of all equipments including LAF or BSC.
[] Rub hands with the help of 70% IPA.
[] Always maintain aseptic condition during handling of standard microorganisms.

Inoculation Technique
  • Opening of Standard Culture vial/ampoule
  • Read carefully label’s instructions of standard culture vial/ampoule.
  • Aseptically break the ampoule/vial under Laminar Air Flow.
  • Remove pellets from vial/ampoule aseptically as per instruction of the label.
  • Tight the container for the next time use after removing pellets.
Inoculation of Standard Microorganisms:
  • Label on the each tube with the name of standard culture.
  • Reconstitute standard culture pellets as per instructions of manufacturer.
  • Aseptically Transfer 1 or 2 pellets of dehydrated culture of bacteria and fungus in the test tubes containing CSB.
  • Incubate test tubes containing bacterial culture at (30 to 35)0C for 3 days and the tubes containing fungi culture at (20 to 25)0C for 5 days. This will serve as mother culture.
  • After incubation, observe the growth of standard culture that should be turbid or settle growth.
  • Transfer & streak from the broth culture on surface of agar slant.
  • Incubate test tubes containing CSA at (30 to 35)0C for 3 days & the SDA tubes containing fungi culture at 20 to 250C for 5 days.
  • Observe good growth, then preserve it at (2 to 8)0C in refrigerator with proper labeling.
  • Discard previous culture by autoclaving at 1210C for 30 minutes.
  • Subculture microorganism to freshly prepared culture media once in a month.
Preparation of spore suspension:
  • Transfer sterilized media under Laminar Air Flow or Bio-safety Cabinet.
  • Keep plate for incubation at 350C for 7 days.
  • After incubation period take out culture with aid of sterilized glass beads & pre-sterilized diluents (0.001 g/L containing Manganese sulfate) by rotating plate.
  • Pour culture suspension along with few of those glass beads in a 100ml flask containing 50ml of sterilized diluents.
  • Heat culture suspension at 700C for 30 minutes or 800C for 10 minutes in a water bath.
  • Cool suspension & then keep inside a refrigerator not exceeding at 40C
  • Don’t use spore suspension more than 60 days.
Preparation of standard culture suspension (Vegetative form):
  • Prepare culture suspension by regular subculture on Nutrient Agar slant or Sabouraud Dextrose Agar.
  • Before using a culture maintained in a slant, subculture the organism in another slant containing a specified medium.
  • Keep the slant for incubation at (30 to 35)0C for bacteria for (24 to 30) hours and at (20 to 25)0C for fungi for (3 to 5) days.
  • Store slant in the refrigerator not exceeding at 40C if not used immediately.
  • Don’t use this suspension at more than 7 days.
Stock Maintenance of Standard Microorganisms:
  • Check expiry date before use of standard microorganisms.
  • Don’t use if the expiry date is exceeded & discard it after autoclaving.
  • Raise requisition for standard culture before exceed of expiry date.
 Report Preparation

Maintain Register of standard culture maintenance Record, Annexure-I.

Download Annexure:

Download the annexure here: Standard Culture Maintenance Record

Maintain and preserve of standard culture and its SOP Read More »

Identification of Microorganisms and its SOP

Identification of Microorganisms; Purpose

To identify Microorganisms.

Identification of Microorganisms; Scope

This SOP applies for identification of Microorganisms in Microbiology Section at XX Pharmaceuticals Ltd.

Definitions
GN-ID System

The GN-ID system employs 12(GNA) or 24(GN A+B) standardized biochemical substrates in microwells to identify the family of Enterobacteriaceae & other non-fastidious Gram negative bacilli (Oxidase negative and positive). The kit is planned for professional laboratory use only.

[] CPG: Colony Pigmentation.
[] CAT : Coagulate test
[] LAT : Latex Agglutination Test
[] ONPG : Ortho-Nitrophenyl β-Galactoside
[] PYR : PYRROLIDONYL ARYLAMIDASE
[] TDA : Tryptophan Deaminase Agent( Indolepyruvic Acid)
[] VP : Voges-Proskauer

Identification of Microorganisms;Responsibilities:
Executive/ Sr. Executive, Microbiology

Selection of culture and identification of Microorganisms.

Assistant Manager, Microbiology

Ensure identification and application of sound technical information.

Head of Quality Assurance

Take initiative to Approval of SOP.

Identification of Microorganisms; Procedure:

Instructions

  • Before handling of micro-organisms, wear sterile latex free gloves, mask, laboratory coat & eye protection (if required).
  • Make sure that all personal ornaments, cell phone are left to prevent unauthorized contamination, before entrance into the test room. The use of Cell phone in the test area is firmly prohibited.
  • Do not touch any identification materials directly because all are hazardous materials.
  • Keep all used materials into specific designated container.
  • The reagents kits are for in vitro use only.
  • Discard all used items by immersion in an appropriate disinfectant e.g. 3% of sodium hypochlorite for 30minutes. Liquid waste containing acid must be neutralized before treatment.
  • Care should be taken when handling additional reagents as they may contain corrosive or irritant materials.
  • Read carefully the leaflet of all reagents before use.
General Requirements for the test
Glass Apparatus :
  • Sterile Screw Capped Test Tube
  • Sterile Pipette 1ml/2 ml/10 ml
  • Glass slide
Media and Reagents :
  • Casein Soyabean Digest Agar(CSDA)
  • Casein Soyabean Digest Broth(CSDB)
  • Cetrimide Agar
  • Hydrogen Peroxide
  • Kovac’s reagent
  • Mac-Conkey Broth
  • MacConkey Agar
  • Mannitol Salt Agar
  • Meat peptone
  • Mineral Oil
  • Neutralized Peptone
  • Nitrate Reagent
  • Oxidase strips
  • PYR Reagent
  • Rapport Vasiliadis Salmonella Broth
  • Sabouraud Dextrose Agar
  • Sterile 0.85% Saline
  • TDA reagent
  • VP I and VP II reagents
  • Xylose Lysine Deoxycholate(XLD) Agar

These media and reagent can be purchased from commercially available manufacturer.

 Others Requirements
  • 70% IPA or ethanol
  • Forceps
  • Micropipette
  • Micropipette sterile Tips
  • Surgical Gloves
  • Surgical Cotton
  • Scissors
Identification of E. coli/ Salmonella/ Others Enterobacteriaceae/ Pseudomonas aeruginosa :
Preparation of Specimens :
  • Isolate bacterial culture by streaking on the slant initially on MacConkey Agar for coli or Xylose Lysine Deoxycholate (XLD) Agar for Salmonella species & Cetrimide Agar for Pseudomonas aeruginosa.
Identification of Staphylococcus aureus:
Preparation of Specimens
  • Isolate the bacterial culture by streaking on the slant initially on Mannitol Salt Agar.
  • Sub-culture on the slant of Casein Soyabean Digest Agar.
  • Perform Staining as per SOP for Staining of Micro-organisms as per approved sop
  • Use always 18 to 24 hours pure culture for identification.
  • Ensure that the isolate bacteria is catalase positive and Gram Positive cocci in clausters in Gram staining test.
 Inoculation and Incubation :
  • Confirm that the bacteria is the genus of Staphylococcus in slide Coagulate test (CAT)
  • Emulsify a single colony from an 18-24 hors culture in the suspending medium supplied in the kit.
  • Mix thoroughly.
  • Carefully peel back the adhesive strip sealing the microwell strip.
  • Do not discard sealing strip as they will be required later.
  • Using a sterile pastuer pipette, add 100 µL of the bacterial suspension to each well of the strip.
  • As a purity check, transfer 1 drop of the bacterial suspension on to the purity plate of Mannitol Salt Agar.
  • Incubate the purity plate aerobically at 35-370C for 18-24 hours.
  • After inoculation overlay wells 10 and 11 with 100 µL of mineral oil. This well is highlighted with a black circle around the well to assist in adding oil to the correct wells.
  • Seal the top of the microwell strip with the adhesive strip removed earlier and incubate at 35-370C for 18-24 hours.
Reading and Addition of  Reagents
  • Remove adhesive strip & record positive reactions the aid of the color chart.
  • Record results on provided forms.
  • Add 1 drop of PYR reagent to well 12. Read & record the results after 10 minutes.
  • Perform nitrate reduction test on well 9 after reading & recording the ONPG result.
  • Add 1 drop of Nitrate A reagent &1 drop of Nitrate B reagent to well and read after 60 seconds.
  • Add small amount of zinc powder, If well 7 remains yellow or colorless after addition of nitrate reagents. After addition of zinc, colorless/yellow indicates positive & red color indicates negative.
  • Record these additional results on the form provided.
 Identification
  • Report in the form the substrates have been organized into triples (set of 3 reactions) with each substrate assigned a numerical value (1, 2 & 4). The sum of the positive reactions for each triplet forms a single digit of the profile number that is used to determine the identity.
  • Enter the profile number into identification software which generates a report of the five likely organisms in the selected database.
  • The software provides identification based on probability in % up to species level.
  • Sub-culture on the slant of Casein Soyabean Digest Agar.
  • Perform Staining as per SOP for Staining of Micro-organisms
  • Use always 18-24 hours pure culture for identification.
  • Confirm that the isolated bacteria is Gram Negative bacilli.
Inoculation and Incubation :
  • Carry out an Oxidase test on the isolate. Oxidase positive organisms can only be identified by inoculating both GNA and GN B microwell strips.
  • Emulsify a single colony from an 18-24 hour culture in 3 ml sterile 0.85% saline for the GN A microwell strip. If both GN A and GN B strips are to be inoculated, the colony should be emulsified in 3-5 ml sterile 0.85% sterile.
  • Mix methodically.
  • Carefully peel back the adhesive strip sealing the microwell strip.
  • Do not discard sealing strip as they will be required later.
  • Using a sterile pastuer pipette, add 100 µL of the bacterial suspension to each well of the strip.
  • As a purity check, transfer 1 drop of the bacterial suspension on to the purity plate of MacConkey Agar/ Xylose Lysine Deoxycholate (XLD) Agar.
  • Incubate the purity plate aerobically at (35 to 37)0C for 18 to 24 hours.
  • After inoculation overlay wells 1,2 and 3 (GN A strip counting from the tabbed end) and well 20 and 24(GN B strip-well 13 is at eht tabbed end) with 100 µL drops of mineral oil.
  • Do not overlay well 20 if isolate bacteria is Oxidase positive. These wells are highlighted with a black circle around the well to assist in adding oil to the correct wells.
  • Seal the top of the microwell strip with the adhesive strip are over wells 7, 11 and 12 in the GN A strip and over well in the GN B strip.
  • GN A and GN B microwell strips are read after 18 to 24 hours incubation for Enterobacteriaceae and after 48 hours for Oxidase positive bacteria.
Reading and Addition of  Reagents :
GN A Strip :
  • Remove adhesive strip & record positive reactions the aid of the colour chart.
  • Record results on the forms provided.
  • Add 2 drops of Kovac’s reagent to well 8. Read & record the results after 60 seconds.
  • Add 1 drop of VP I reagent and 1 drop of VP II reagent to well 10 and read after 15-30 minutes.
  • Add 1 drop of TDA reagent to well 12 and read after 60 seconds.
  • Perform the nitrate reduction test on well 7 after reading and recording the ONPG result.
  • Add 1 drop of Nitrate A reagent and 1 drop of Nitrate B reagent to the well and read after 60 seconds.
  • Add small amount of zinc powder, If well 7 remains yellow or colorless after addition of nitrate reagents, After addition of zinc, colorless/yellow indicates positive and red color indicates negative.
  • Record these additional results on the form provided.
 GN B Strip

[] Remove the adhesive strip and record all positive reactions with the aid of the color chart.

Record the result

[] The gelatin well 13 must be read after 18-24 hours for Enterobacteriaceae and after 48 hours for Oxidase positive isolates. A positive gelatin liquefaction result is indicated by black particles visible throughout the well.
[] Arginine well  is interpreted differentially after 24 hours an 48 hours incubations as below :

After 24 hours:

[] Yellow indicates negative
[] Green/Blue indicated positive.

After 48 hours (Oxidase Positive organisms)

[] Yellow/Green : Negative
[] Blue : Positive

Identification :

[] Report form GN A+B, the substrates have been organized into triples (set of 3 reactions) with each substrate assigned a numerical value (1, 2 & 4). The sum of the positive reactions for each triplet forms a single digit of the profile number, that is used to determined the identity.
[] Enter the profile number into identification software which generates a report of the five likely organisms in the selected database.
[] The software provides identification based on probability in % up to species level.

Identification of Microorganisms and its SOP Read More »

Staining of Microorganism and its Standard Operation Procedure

Staining of microorganism; Purpose

To stain the microorganism in order to identify the bacteria or fungi.

Scope

This SOP is applicable to stain bacteria and Yeast/mould in Microbiology Section of General Building at XX Pharmaceuticals Limited.

Definitions 
Staining

This the auxiliary technique which is mainly used to enhance contrast in microscopy on a microscopic image. The main application of stain and dyes in medicine and biology sector to highlight the structure of biological tissue.

Gram Staining 

Gram stain is the most useful staining technique engaged in bacteriology, is a differential stain. By using this technique, it is possible to divide bacteria into two different groups- Gram Positive & Gram Negative.

Endospore Staining

Spore stain is a most useful staining technique engaged in bacteriology is a structural stains. By this technique, it is possible to detect the presence & position of endospore in the bacteria.

Responsibilities:
Executive/ Sr. Executive, Microbiology

Initiative of subculture of Microorganisms, perform staining & report preparation.

Manager, Microbiology

Confirm staining techniques, safety report checking, document preservation & application of sound technical information.

Head of Quality Assurance

Approval of SOP

Procedure:

Instructions
  • Standard microorganisms are usually non-pathogenic but those are unscrupulous pathogen. So before handling it, wear protective items such as sterile wear sterile latex free gloves, laboratory coat & eye protection (if necessary).
  • Don’t move vigorously into test area. Move always softly.
  • After completion of subculture or transfer of pellets, disinfect outer surface of the vial or test or plate with 70% IPA.
  • Remove all used items those are directly contacted with standard micro-organisms. Leave it at designated containers safely.
  • Ensure that the waste container is tightly capped until perform autoclaving.
  • Don’t touch the apparatus directly in open hands those are used.
  • Make sure that all personal ornaments, cell phone are left to prevent unauthorized contamination, before entrance into the test room.
Simple Staining
Staining Reagents
Methylene blue Stock Solution :
  • Methylene Blue         2.g
  • Distilled Water          100 ml
Methylene blue Staining Solution :
  • 0.2 % of Methylene Blue Solution  12.5 ml
  • Distilled Water                                87.5 ml
Crystal Violet Solution
  • Crystal Violet            2.0 g
  • Ethyl alcohol 95%    20 ml
  • NH4 Oxalate            0.8 g
  • Distilled Water         100 ml
Carbol Fuchsin(Zeihl-Neelsen)  Solution
  • Fuschin                     1 g
  • Ethanol                     10 ml
  • Phenol                       5 g
  • DistilledWater           200ml

Dissolve Fuschin in alcohol and dissolve phenol in water, then mix the two solutions.

 Apparatus
  • Glass slide 3 x 1 inch
  • Pipettes
  • Gas Burner or spirit Lamp
Staining Technique:
  • Clean & dry microscope slides thoroughly.
  • Flame the surface in which the smear is to be spread.
  • Flame the inoculating loop properly.
  • Transfer a loop full of tap Water to the flamed slide surface.
  • Reflame the loop making sure that the entire length of the wire that will enter the tube has been heated to redness.
  • Remove the tube cap with the fingers of the hand holding the loop.
  • Flame the tube mouth.
  • Touch inoculating loop to the inside of the tube to make sure it is not so hot that it will distort the bacterial cells;  then pick up a pinhead size sample of the bacterial growth without digging into the agar.
  • Reflame tube mouth, replace can, and put tube back in the holder.
  • Disperse bacteria on the loop in the drop of water on the slide and spread the drop over an area the size of a dime.  It should be a thin, even smear.
  • Reflame the inoculating loop to redness including the entire length that entered the tube.
  • Allow the smear to dry thoroughly.
  • Heat-fix the smear cautiously by passing the underside of the slide through the burner flame two or  three times.
  • Test the temperature of slide after each pass against back of the hand.  It has been heated adequately when it feels hot but can still be held against the skin for several seconds.  Excessive heat will distort the cells.
  • Stain smear by flooding it with one of the staining solutions & allowing it to remain covered with stain for time designated below.
  • Methylene blue: 1 minute
  • Crystal violet: 30 seconds
  • Carbol Fuchsin: 20 seconds
  • During staining the slide may be placed on the rack or held in the fingers.
  • At the end of the designated time rinse off the excess stain with gently running tap water.  Rinse thoroughly.
  • Wipe the back of the slide and blot the stained surface with bibulous paper or with a paper towel.
  • Place the stained smear on the microscope stage smear side up and focus the smear using the 10x objective.
  • Choose an area of the smear in which the cells are well spread in a monolayer.  Center the area to be studied.
  • Apply oil directly to the smear, and focus the smear under oil with the 100X objective.
  • Draw the cells observed.

 

Gram Staining Method
Stain and Reagents
Crystal Violet Solution
  • Crystal Violet                 2.0 g
  • Ethyl alcohol 95%         20 ml
  • NH4 Oxalate                 0.8 g
  • Distilled Water              100 ml
Gram’s Iodine
  • Iodine Crystals              1.0 g
  • Potassium Iodide          2.0 g
  • Distilled Water              100 ml
Docolorizer :
  • Acetone                         50 ml
  • Ethanol 96%                  50 ml
Counterstain :
  • Safranin                         2.5 g
  • Ethanol 95%                 100 ml
  • Distilled Water              100 ml
Apparatus :
  • Glass slide 3 x 1 inch
  • Pipettes
  • Gas Burner or spirit Lamp
Staining Technique
  • Use always young culture of (18 to 24) hours that the differentiation in cell wall structures is retained.
  • Do not use old cultures due to lose Gram Positiveness.
  • Make smear, and dry in air and fix by flaming.
  • Stain with crystal violet for about 30 seconds.
  • Rinse with the water.
  • Cover smear with Gram’s iodine for about 30 seconds.
  • Rinse with the water.
  • Decolorize with 95% ethanol. For a thin smear, 10-20 seconds is long enough; after the proper time interval, alcohol
  • Drippings from the slide are no longer colored.
  • Rinse with the water.
  • Counterstain with safranin solution for 20-30 seconds.
  • Rinse with water and blot dry.
  • Examine under the oil-immersion objectives.
Interpretation of Result :
  • Gram positive bacteria retain the crystal violet dye after de-colorization and appear deep blue or purple colour.
  • Gram negative bacteria are not capable of retaining the crystal violet dye after de-colorization and are counterstained red or pink by the safranin dye.
Endospore staining :
Stain and reagents :
  • Malachine Green solution
  • Malachite green        5 g
  • Distilled Water          100 ml
Counterstain Solution
  • Safranin                   2.5 g
  • Ethanol 95%           100 ml
  • Distilled water         10 ml
Apparatus
  • Glass slide 3 x 1 inch
  • Pipettes
  • Gas burner
Slide Cleaning :
  • Clean the slide by immersion in concentrated Sulphuric Acid saturated with Potassium dichromate for several days for removal of grease from slide.
  • Place drop water on the surface of the slide, if water is spread over its surface indicates the slide is cleaned properly.
Staining Technique
  • Prepare smear, dry in air and fix by flaming.
  • Place the slides on a staining rack.
  • Cover the smear and keep saturated with malachite green 5% aqueous solution and continue heating for 5 minutes.
  • Wash gently with the water.
  • Counterstain with safranin for 30 seconds.
  • Wash with water and blot dry.
  • Examine under the oil-immersion objectives.
Interpretation of result :

The endospore stains green and the remainder of the cell (or a cell without an endospore) stains light red.

The phase microscope is effective in observing the endospore without staining where it appears as a dense white structure in the cell. If a phase microscope is available, observe the unstained endospore in cultures of Bacillus and Clostridium species.

Staining of Microorganism and its Standard Operation Procedure Read More »

Effluent Water Test and Its Standard Operating Procedure

Effluent Water Test ; Purpose:

To ensure that effluent water is analyzed to meet In-house specification in order to minimize environmental pollution.

Scope:

This SOP applies for analysis of effluent water in Quality Control Section and Microbiology Laboratory at XX Pharmaceuticals Limited.

Definition/Abbreviation:  

BOD:  Biological Oxygen Demand

Responsibilities:

The roles and responsibility is as follows:

Microbiologist/Officer, QC

Sample collection and analysis of effluent water & test report preparation.

Manager, Microbiology/Asst. Manager, QC

Ensure sampling, analysis, documentation & application of sound technical information.

Manager, Quality Assurance

Approval of SOP.

Procedure:

Instructions
  • Care should be taken during sampling because effluent water is hazardous and toxic.
  • Wear gloves, mask during sampling and testing.
  • Discard all used materials, glassware, gloves at the end of work after autoclaving.
Sample Collection:
  • Take clean & dry of 2 Liters flask for chemical test sample.
  • Sterilize sampling container at 1210C for 15 minutes for microbiology test.
  • Take effluent water sample at least 2 Liters for chemical test.
  • For microbiology test, take sample into three of 250 ml BOD bottle.
  • Drop cap on the mouth of BOD bottle tightly.
  • Ensure the BOD bottle is free from any bubble.
  • Don’t expose container outside area of Laboratory.
  • Carry out sample into Quality Control & Microbiology Laboratory.
Sample Preservation

Preserve sample at 2 to 80C for not more than 24 hours.

Test Frequency

Carry out test once in every three months.

 Chemical & Microbiological tests as follows

Perform the test as per Analytical Method of Effluent Water.

Report preparation:

Report of the test result in Effluent Water Test Report, Annexure-I.

 Distribution of Result
  • After completion of analysis, inform status to the Engineering Department.
  • If any test result found out of specification, repeat test to be done.
  • If repeat test result found out of specification then inform to Engineering Department for corrective action.
  • After corrective action, collect the sample & carry out the test.

Annexure:

Download the Annexure Here: Report

Effluent Water Test and Its Standard Operating Procedure Read More »

Bioassay Procedure and Its Sop

Bioassay; Purpose

Bioassay; To determine the potency of antibiotics of raw materials & products which are specified in different Pharmacopeia.

Bioassay; Scope

This SOP is applicable for Biological Assay of Antibiotics in Microbiology Section at XX Pharmaceuticals Limited.

Definitions
Microbial Assay

In Microbial assay the potency or concentration of a chemical substance (especially antibiotics) may be determined by its effect on the growth of a defined microorganism.

Responsibilities
Executive/Senior Executive, Microbiology

Assay plate preparation, assay dilution, inoculation, zone reading and report preparation.

Manager, Microbiology

Ensure that all activities of Biological assay, document preservation & application of sound technical information.
Checking SOP that the relevant technical information is applied.

 Bioassay Procedure
Instructions
  • Standard microorganisms are usually non-pathogenic but those are unscrupulous pathogen. So before handling it, wear protective items such as sterile wear sterile latex free gloves, laboratory coat & eye protection (if required).
  • Advised to move softly at Test area not vigorously.
  • After completion of sub-culture or transfer of pellets, disinfect the outer surface of vial or test or plate with 70% IPA.
  • Remove all used items those are directly contacted with standard micro-organisms. Leave it at designated containers safely.
  • Ensure waste container is properly capped until autoclaving.
  • Don’t touch apparatus directly in open hands those are used.
  • To lessen the contamination, make sure that all personal ornaments, cell phone are left before enter into the test room/area’.
Sterilization of Apparatus & Glassware:
  • Sterilize all glassware including Latin Square Plate and others heat stable apparatus at 2000C for 60 minutes in hot air oven using a validated process.
  • Use the glassware when the temperature reduce below 400′
Preparation of Culture Media:
  • Select the media & diluents as per instruction of BP or USP.
  • Prepare 300 ml of particular media as per indication by manufacturer instructions.
  • Bring to boil for dissolve completely.
  • Sterilize at 1210C for at least 15 minutes.
  • Cool media approximately to 450C to 500C
  • Allow to solidify the agar media to prepare the slope.
Preparation of Test solution
  • Prepare different concentrations of Test Solution to determine of the lowest dose for detectable zone of inhibitions.
  • Select & prepare two concentrations of the Test solution as “High Dose” and “Low Dose”.
Preparation of Standard solution
  • Prepare different concentrations of Standard Solution to determine of the lowest dose for detectable zone of inhibitions.
  • Select & prepare two concentrations of Standard solution as “High Dose” & “Low Dose”.
Preparation of Microorganisms Suspension:
For Spore suspension preparation
  • Prepare 140ml of Nutrient agar medium.
  • Aseptically Pour the medium on a petri plate (190mm).
  • Allow the medium to solidify.
  • Keep plate in refrigerator for 30 minutes.
  • After 30 minutes take out plate & streak whole plate with the desired organism aseptically.
  • Keep plate for incubation at 350C for 7 days.
  • After incubation period take out the culture with the aid of sterilized glass beads & pre-sterilized saline water by rotating plate.
  • Pour culture suspension along with few of those glass beads in a 100ml flask containing 50ml of sterilized saline.
  • Heat culture suspension at 700C for 30 minutes in a water bath for spore formation.
  • Cool suspension & then keep inside a refrigerator between (2 to 8)0
  • Don’t use the spore suspension more than 60 days.
For Maintenance of Sub-culture of Vegetative bacteria
  • Before using a culture maintained in a slant, subculture the organism in another slant containing a specified medium.
  • Keep slant for incubation at (30 to 35)0C for 24 to 30 hours.
  • Store the slant in the refrigerator at not more than 7 days.
 Method: Plate Diffusion:
  • Select Latin Square Plate of 12” X 12” size.
  • Place plate on a leveled surface after sterilization.
  • To the medium( 45 to 50)0C add the organism mentioned in above chart for a particular antibiotic in required amount.
  • Shake flask gently to distribute organism throughout the medium.
  • Pour medium on plate & allow it to stand for 30 minutes before placing lid in position.
  • Transfer plate into refrigerator.
  • When required for use, cut cups in agar by means of a sterile cork borer of 8mm diameter.
  • Remove each disc of agar with a “spear” so that the surrounding is not lifted.
Application of solution to Assay Plate :
  • Enter details of the sample numbers, weight & dilutions on the assay report form, after diluting the standard and test solutions, There is an assay report form for each plate.
  • Concentrated solutions are coded with H (High dose) and the lower concentrated solutions are coded with L (Low dose).
  • Apply using a standard (100 ±1) µL the solutions to the assay plate in the order of the design.
  • Starting at top left hand corner & working from left to right across the rows down to the bottom right hand corner.
  • Once started, plating out should be continuous, as it is important that solutions are placed in cups at regular interval.
  • Keep the plate about one hour for proper diffusion.
  • After diffusion lid the plate with glass lid.
Incubation of Assay Plate

Incubate assay plate for (16 to 20) hours at 370C for antibiotic or 250C for antifungal.

Measurement of the Zone Diameters
  • Place the assay plate on a photographic light box.
  • Measure zone of inhibition using Varnier calipers.
  • Start at top left hand corner and measure the diameter of the zone accurately.
  • Continue measuring zones from left to right on row 1, then right to left on row 2.
  • Repeat the procedure until all 64 zones have been properly measured.
Bioassay; Calculation of Potencies:
  • Sum high & low doses for each standard ( S1&S2)
  • Sum high & low doses for each test sample (T1& T2)
  • Substrate test treatment totals from standard treatment total. This will give a plus or a

Minus figure = D, D = (T1 +T2)-(S1 +S2).

  • B = (Sum of high doses of test, T1 – Sum of low doses of test solution, T2) + (Sum of high doses of

Standard, S1– Sum of low doses of standard, S2)

  • Calculate the “Dilution factor of high-test sample (F)” by dividing “Weight of sample” taken by “Total

Volume of dilution” up to high doses.

  • Log ratio of dilution (I) = Log (High dose concentration ÷ Low dose concentration)
Actual weight

Calculate “Potency of High Standard (H) = ———————– X. High dose concentration                                                             Theoretical weight

Potency (P) = Antilog (D/B x I) x F x H.

Report the result in Biological Assay Report, Annexure-I.

Download Annexure: Bioassay Report

Bioassay Procedure and Its Sop Read More »

Environmental Monitoring Procedure and its Sop

Environmental Monitoring; Purpose

Environmental Monitoring; To describe the procedure for Environmental monitoring.

Scope

Environmental monitoring in  XX Pharmaceuticals Ltd

Definitions
Environmental monitoring:

Monitoring of viable and non-viable quality of a controlled environment

Particulate count:

[] Enumeration of non-viable particulate of specific size from a particular volume of air of a controlled
Environment.
[] Settle Plate: Exposure of petri-plates of nutrient media in a controlled environment to estimate viable
Microorganisms from the environment.
[] TSA: Tryptone Soya Agar
[] CFU: Colony Forming Unit

Responsibilities

The roles and responsibility is as follows:

Lab. Attendant

Room preparation for Test

Executive, Microbiology

Carry out the test and incubation & documentation

Sr. Executive, Microbiology

To ensure test, incubation, report checking, document preservation & application of sound technical information.

Head of Plant

Review of the SOP & the relevant technical information is applied.

Head of Quality Assurance

Take initiative to Approve of this SOP.

Procedure:

Instructions
  • Don’t rub during contact plate sampling.
  • Use the sterile filter holder.
  • Place the filter paper on the filter holder carefully under laminar airflow.
  • Try to avoid unwanted personal contamination during air sampling.
  • Monitoring to be carried out before production hours. (Sterile products)
Non-viable Particle monitoring:
  • Bring the laser particle counter into the specific monitoring area.
  • Enter into clean room, wearing approved designated dress. When entering into the clean area, before taking reading make sure that all the doors remain closed.
  • Operate the Particle counter following approved SOP.
  • Take count of different several position for each room as indicated in sampling point. Count the number particles (5µ and 0.5 µ) form each sampling point. The average of the counted particle indicates the total particles of a room.

The minimum sampling time should be as per following formula (Following EN ISO 14644-1)

Vs=(20/Cn,m ) x 100

Where,

  • Vs = is the minimum single sampling volume per sampling point, expressed in liter.
  • Cn,m = is the class limit (number of particles per cubic meter) for the largest considered
    particle size, specified for the relevant class.
  • 20 = is the defined number of particles that could be counted if the particle concentration
    were at the class limit.
Specification: Follow Annexure-III.
Write down the result in the format of Annexure-I.

 

Environmental Monitoring

Viable count:

Settle Plate
  • Prepare, sterilize & dispense the media TSA into the petriplates and pre-incubate the plates.
  • Check the pre-incubated plates for any evidence of microbiological contamination under the LAF bench.
  • Discard the plates contains microbiological growth.
  • Decontaminate the external surface of petriplates with sterile cloth /cotton soaked in a sanitizing agent (70% IPA).
  • Place required number of petriplate in a sterilized /sanitized SS container; close the lid of SS container.
  • Transfer SS box to the area to be monitored.
  • Enter respective area as per the SOP of Entry and Exit procedure.

Mark Petri plates with the following details-

  1. Name of the sampling point
  2. Room No.
  3. Date of exposure
  • Place petriplates on corresponding designated plate exposure area and remove
    the upper lid of the petriplates. Note the beginning time of the exposure and write it on
    the plate.
  • Place upper lid on edge of petriplates in slanting position.
  • Expose media plates at sampling point for Maximum 4 hours.
  • After completion of exposure, close petriplates with lid.
  • Collect petriplates in the SS container and bring back exposed plates to microbiology Laboratory.
  • Incubate all exposed petri plates in inverted position in laboratory Incubator.
  • Incubate at (22.5 ± 2.5)°C for mold and Yeast for 72 hours followed by another 48 hours for bacteria at (32.5 ± 2.5)°C. After incubation count the number of colony forming units (CFU) per plate per sampling point with colony counter.
  • Incubate an unexposed media filled petriplates along with the exposed plates and mark it as negative control.
  • Count the number of Colony Forming Units (CFU) per plate per location with colony counter. The average of colony indicates total CFU of a room.
Write down observation in the format attached as Annexure-II.

Air Sampling:

  • Set instrument for desired sampling time & flow rate as per Approved SOP.
  • Take air sampler to location where air is to be sampled, hold it with filter facing at required direction and take air sample following approved SOP.
  • Collect filter under laminar airflow & place it inside on petriplates containing TSA[Tryptone Soya Agar ] media.
  • Incubate all exposed petri plates in inverted position in the microbiology laboratory Incubator. Incubate at the (22.5 ± 2.5)°C for mold & Yeast for 72 hours followed by another 48 hours for bacteria at (32.5 ± 2.5)°C. After incubation count the number of colony forming units (CFU) per plate per location with colony counter.
  • Follow sampling location.
  • Record observation in format attached as Annexure-II.
  • Calculate number of organisms per cubic meter of air. Average colony indicates total cfu of a room.

Surface monitoring (By swab sampling):

  • Use sterilized swab or sterilize the swab in the autoclave.
  • Place required number of sterilized swab sticks with tube containing 5 ml of sterile saline
    solution in a Sterilized SS container & tightly secure lid of the SS container.
  • Transfer SS box to area to be monitored.
  • Enter respective area as per SOP of entry and exit procedure.

Remove swab sticks with tubes from the SS box & take it to the location to be monitored and Mark tube with following details:

  1. Location number or Name of the location
  2. Swab No.
  3. Date of sampling
  • Hold swab stick from bottom & place tip on surface to be monitored. Gently wipe the swab bi-directionally to cover an area about 25 cm2.
  • Perform swab sampling for each defined locations.
  • Keep swab sample standing in the SS container & bring it to Laboratory.
  • Gently vortexes swab sampling tube containing swab stick & pour contents in filter holder funnel and filter it. Uses the respective SOP.
  • Rinse tube with 3 x 10 ml of sterile saline solution.
  • Filter test sample under partial vacuum.
  • Rinse Funnel with the portions of sterile Purified Water. This flushes residue from walls of funnel & helps to secure a uniform distribution of colonies on filter surface. Upon completion of rinse & filtration process, shut off vacuum.
  • Transfer membrane filter with sterile smooth-tip forceps on to Microbial content test agar (TSA) plate.
  • Place filter with a rolling motion to avoid entrapment of air.
  • Keep a negative control by filtering 100 ml Purified Water(Sterile) before filtering actual test sample.
  • Pass 20 to 30 ml of sterile Purified Water through funnel, between different test samples when the same funnel used for multiple sample.
  • Incubate all exposed petriplates in inverted position in microbiology laboratory Incubator. Incubate at (22.5 ± 2.5)°C for mold and Yeast for 72 hours followed by another 48 hours for bacteria at (32.5 ± 2.5°)C. After incubation count number of colony forming units (CFU) per plate per location with colony counter.
  • Count number of colony forming units (CFU) per plate per location with colony counter.
Note down the observation in the format attached as Annexure-II
Surface monitoring (By contact plate):
  • Fill Petridishes with TSA culture medium & pre-incubate.
  • Take off the lid of plates.
  • Invert & press agar surface for 10 seconds onto surface to be examined.
  • Replace lid & mark plate with appropriate data.
  • Clean sampling area on surface in order to remove any remaining of agar.
  • Return plates to laboratory.
  • Incubate all exposed petriplates in inverted position in microbiology laboratory Incubator. Incubate at (22.5 ± 2.5)°C for mold and Yeast for 72 hours followed by another 48 hours for bacteria at (32.5 ± 2.5°)C. After incubation count number of colony forming units (CFU) per plate per location with colony counter.
  • Take count of visible colonies within mean of plate
  • Express results as CFU per contact plate.
  • Perform appropriate identification of germs found by surface monitoring..Classified area should free of pathogenic microorganism.
Note down the observation in the format attached as Annexure-II.
Sampling Location:

Determine Number of sampling location by following formula.

NL    = √A

Where,

NL   = the minimum number of sampling locations, rounded up to a hole number.

A= Area of the clean room or clean air controlled space in m2.

Environmental Monitoring Procedure as per Pharmacopeia

Download All Annexure Here: Environmental Monitoring

Schedule: Environmental Monitoring

Environmental Monitoring Procedure and its Sop Read More »

Suitability of Microbial Count Method & its SOP

Suitability of Microbial Count Method; Purpose

Suitability of Microbial Count Method; To confirm the ability & the suitability of the test to detect microorganisms in the presence of a product or Raw Materials as per the In-house or Pharmacopoeia specifications.

 Scope

This SOP is applicable for Microbial Count Method Validation in Microbiology Section of XX Pharmaceuticals Limited.

 Definitions

Microbial count Suitability: Microbial Count suitability is to confirm that the test dilution is free from any type of interfering substances or antimicrobial properties that will recover by dilution or the addition of a neutralizer to detect microorganisms in the presence of the product.

  • CSDA: Casein Soybean Digest Agar
  • CSDB: Casein Soyabean Digest Broth
  • LAF: Laminar Air Flow
  • SDA: Sabouraud Dextrose Agar
  • SDB: Sabouraud Dextrose broth
Responsibilities

The roles and responsibility is defined as follows:

Executive/ Sr. Executive, Microbiology

Preparation & inoculation of standard culture, carry out test & arrange appropriate document preparation.

Asst. Manager/Manager, Microbiology

Ensure of method suitability, documentation and application of sound technical information.

Head of Quality Assurance

Taking Initiative to Approval of this SOP

Procedure

Instructions
Safety Precautions
  • When enter into the test area, wear sterile latex free gloves, Laboratory coat and eye protection (if required).
  • To prevent unauthorized contamination, make sure that all personal ornaments, cell phone are left before enter into the test room. The use of Cellular phone in the test room is strictly prohibited.
  • Don’t move vigorously into the test area. Move always gently.

General Requirements

Glass Apparatus
  • Pipette 2 ml, 10 ml
  • Sterilized 90 mm Glass Petridish
  • Screw capped Conical Flask 100 ml
  • Screw Capped Test Tube
  • Volumetric Flask 500 ml
  • Volumetric Flask 1000 ml
Media and Reagents
  • Casein Soyabean Digest Agar(CSDA)
  • Casein Soyabean Digest Broth(CSDB)
  • Meat peptone
  • Neutralized Peptone
  • Sabouraud Dextrose Agar
  • Sabouraud Dextrose Broth

These media can be purchased from commercially available manufacturers.

 Others Requirements
  • 45 µm Membrane Filter
  • 70% IPA or ethanol
  • Filtration Unit( sterilized filter disk and filtering funnel)
  • Forceps
  • Glass spreader
  • Scissor
  • Surgical Cotton
  • Surgical Gloves
General Procedures
Test Conditions
  • Wear gloves, mask/beard mask Headgear before entrance into Testing Room.
  • Disinfectant hands, the outer surface of test sample, LAF workstation with the help of 70% IPA or ethanol before starting the test.
  • Carry out the test under LAF to avoid any type of contamination.
  • Monitor the test area microbiologically using Microbial Air Sampler at each working day.
Culture Media Preparation
  • Prepare the different culture media as per the requirement.
  • Weigh the mentioned amount as per manufacturer label into appropriate flask.
  • Bring to boil completely to dissolve the media.
  • Sterilize at 1210C for 15 minutes or as per Manufacturer label.
  • Store the prepared culture media in air tight flask at controlled environment.
  • Store prepared agar media at (2-8)0C
  • Preserve dehydrated culture media up to its expiry date.
  • Never use expired culture media.
  • Use the agar media when the temperature reduce to 450C and cools in case of the broth media.
Stock Buffer Solution
  • Take 34 g of Potassium Dihydrogen Phosphate[KH2PO4] in a 1000 ml volumetric flask.
  • Dissolve in 500 ml Purified Water, adjust to pH [7.2 ± 0.2] then dilute to 1000 ml with Purified Water.
  • Dispense 90 ml into each screw capped flask[Approx. 11 containers].
  • Sterilize at 1210C for 15 minutes.
  • Store the prepared buffer at 2-80C for a validated period.
Glassware Cleaning & Sterilization
  • Clean glassware by 1% detergent initially then rinse with sufficient tap water.
  • Rinse finally with sufficient Purified Water to remove the residual content of detergent.
  • Sterilize glassware at 2000C for 1 hour.
 Sample Preparation
Water-soluble samples

Take 1 gm or 1 ml into the 9 ml CSDB [Casein Soybean Digest Broth] or phosphate buffer or Sodium chloride peptone solutions.

Water-insoluble samples

Take 1 g or 1 ml into the 9 ml CSDB [Casein Soybean Digest Broth] or phosphate buffer or Sodium chloride peptone solutions and add 0.1% Polysorbate 80.

Fatty Products

Dissolve with Isopropyl Myristate sterilized by filtration with low amount of Polysorbate 80 or anther non-inhibitory sterile surface active agent  or necessary heat not more than 450C.

Inoculation and Dilution:
  • To maintain of not more than100 cfu, add adequate volume of suspension of inoculums to the sample.
  • Add the inoculums suspension not more than 1% of diluted product.
  • Prepare lowest possible dilution for acceptable microbial recovery of sample.
  • Add neutralizer for removal of Interfering factor when [If] the sample contains any antimicrobial properties.

Follow Table-1 for the inactivators of  Antimicrobial agents.

If growth is inhibited, then increase use of diluents or membrane filtration or combination of all above.

 

Suitability of Microbial Count Method

 

Suitability of Counting Method:

[] Membrane Filtration Method

[] Most Probable Number Method

[] Pour Plate Method

[] Surface-spread plate Method

Pour Plate Method :
  • Add 1 ml prepared sample to the 90 mm diameter Petridish
  • Pour (20~25) ml of Sabouraud Dextrose Agar(SDA) for fungi and Casein Soybean Digest Agar(CSDA) for Bacterial count both media being not more than 450
  • If larger Petridish [more than 90 mm diameter] is used amount of media to be increased accordingly.
  • Perform plate count methods at least in duplicate for each medium and use the mean count of the result.
  • Inoculate the microorganisms not more than 100 cfu as indicated Table 2.
  • Mix properly & incubate CSDA plate at (30~35)0C for 3 days, SDA plate at (20~25)0C for 5 days.
  • After incubation, count the colony on each plate.
  • Take arithmetic mean of the count per medium.
Surface-Spread Plate Method
  • Add (20~25) ml of SCDA and SDA to 90 mm diameter petridish at least duplicate.
  • Allow to solidify and dry the plate under Laminar Air Flow cabinet or incubator.
  • Spread not less than 0.1 ml (equal to or less than 100 cfu) of each microorganisms as indicated in Table 1 on the surface of medium
  • Incubate at CSDA plate at (30~35)0C for 3 days, SDA plate at (20-25)0C for 5 days.
  • After incubation, count the colony of each plate.
  • Take arithmetic mean of the count per medium.
Membrane Filtration Method
  • Use the membrane filter which nominal pore size is not more than 0.45µm.
  • Filter prepared sample through membrane.
  • Rinse membrane filter with sterile 0.1% meat peptone solution or any others suitable diluents for neutralization of the sample.
  • Add inoculums to filter as indicated in Table 1 & rinse again.
  • Transfer filter on the surface of CSDA plate & SDA plate.
  • Incubate CSDA plate at (30 to 35)0C for 3 days, SDA plate at (20 to 25)0C for 5 days.
  • After incubation, ten count the colony of each plate.
  • Take arithmetic mean of the count per medium.
Test Control

Negative Control: Use diluents in place of test preparations. There must be no growth found in the negative control. If found any growth in the negative control, then the test is invalid & repeat the test.

 

Suitability of Microbial Count Method

Result and Interpretation

Mean count of any of test microorganisms not differing by a factor greater than 2 from value of the control defined in absence of product must be obtained.

Repeat test by increasing neutralizer or dilution or any treatment for overcome of antimicrobial properties of products. If the above criteria cannot be met for one or more microorganisms.

Test Report Preparation

Prepare Report the result in Suitability Report of Microbial Count Method, Annexure-I.

Annexure

Annexure-I: Suitability of Microbial Count:
Suitability Test Report of Microbial Count Method

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Microbiological Media disposal of used media & its sop

Microbiological Media disposal; Purpose

Microbiological Media disposal; To dispose of the used media properly in order to lessen Microbiology Laboratory Contamination as well as environmental pollution.

 Scope

This SOP is applicable for the disposal of used Media in the Microbiology Laboratory at XX Pharmaceuticals Ltd.

Definition

N/A

Responsibilities

The roles and responsibilities are as follows:

Laboratory Attendant

Clean & disinfect used media

Executive/ Sr. Executive, Microbiology
  • Monitor disposal activity accordingly.
  • Follow the instructions of this procedure appropriately.
  • Follow the instructions of this procedure properly.
Asst. Manager, Microbiology
  • Confirm proper disposal of used media.
  • Confirm that this procedure is kept up to date.
  • Confirm suitable personnel from the section are trained in this practice.
  • Confirm that SOP is technically sound and reflects the required practices.
 Head of Quality Assurance

Approval of this SOP

Procedure

Instructions
  • Appropriately wear heat-resistant gloves, eye protection, and laboratory coat during handling autoclaved media.
  • Avoid autoclaving the sealed containers or completely filled bottles with narrow necks as they may explode.
  • Don’t expose any used media container or plate outside the Laminar Air Flow cabinet.
  • Wash and disinfect both hands after handling used media.
Collection of Used Media
  • Wear suitable garments, gloves, and mask.
  • Wear safety goggles if hazardous media are subject to being discarded.
  • Collect all the media to be disposed of in the designated vessel after use.
  • Close the mouth of the vessel tightly.
 Sterilization
  • Attach the Autoclave Tap with the vessel.
  • Place the vessel into a sterilizer and sterilize at 1210 C & 15 lbs for 30 minutes.
  • Check that the color of the autoclave tap is turned black.
Discard Method
  • After autoclaving, collect the media in a specific container when the temperature comes down to 500 to 550 C and overlay the media with 40% formaldehyde solution.
  • Keep the media for 30 minutes.
  • Dispose of the media into the drain which is linked with ETP.
  • Rinse the vessel properly with hot water.
  • Wash the vessel with detergent.
  • Disinfect the whole vessel with 70% Iso Propyl Alcohol and dry the vessel.
Record Maintain:

Maintain Register of Media Disposal Record in Annexure-I.

Download the Annexure: Media Disposal Record

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Laboratory Cleaning and Sanitizing of Microbiology, Quality Control, PD

Laboratory cleaning is the vital part a pharmaceutical factory. Here Microbiology, Quality Control, Product Development Laboratory cleaning procedure has been clearly defined.

Purpose

To ensure proper cleaning and sanitizing of Quality Assurance Department in order to prevent contamination.

Scope

This SOP applies for cleaning and sanitizing of Quality Assurance Department of XX Pharmaceuticals Limited.

Definitions
Disinfectants

The specific substances which are used on the nonliving objects/ surface of the objects to kill the selective microorganism which are present on the objects/ surface of the objects. It’s not essential to kill all type of microorganism especially bacterial spores [non-resistant bacteria].

All type of Disinfectants are less effective than sterilization which kills all type of living organism. Antimicrobial agents like antibiotics are different from Disinfectants which [antibiotics] kill microorganism within the body.

Antiseptics

The specific substances which are used on the living objects/ surface of the objects to kill the selective microorganism which are present on the living objects/ surface of the objects.

 Cleaning agents

The specific substances which are found generally in liquid but not limited to, use to remove dust, dirt, stains, bad smells, and clutter on the specific surfaces. The cleaning agents are used in beauty, health, to avoid shame, to absence of offensive odor, prevent spreading of dirt, contaminants to oneself and surroundings. It can kill bacteria and clean it.

Responsibilities:

The roles and responsibility is as follows

Cleaner/Lab. Attendant

Preparation of Cleaning & disinfectants solution, Cleaning & Disinfection

Microbiologist

Monitor of cleaning & disinfection

Asst. Manager, Microbiology/QC/PD

Ensure of Laboratory cleaning, disinfection and application of sound technical information.

Head Quality Assurance

Take initiative to approve of this SOP

Procedure

Instructions
  • Use gloves to handle the disinfectants, cleaning solution and wastage materials.
  • Wear gloves, mask, specific Footwear and suitable garments before entrance into Microbiology Testing area.
  • Disinfect the outer surface of the apparatus before transfer into Microbiology Testing area.
Preparation of Cleaning agents & Sanitizer :
Preparation of 5% Savlon/Dettol Solution:

Dilute 50 ml of Dettol/ Savlon Liquid to 1000 ml with Purified Water.

Preparation of 250 to 300 ppm Chlorine Solution:

Dilute 6 ml of Chlotec (Chlorine solution) Solution to 1000 ml Purified Water.

Preparation of Detergent Solution:

Dissolve 10 g detergent powder in Purified Water & dilute to 1000 ml with same solvent.

Cleaning and Sanitizing Microbiology Laboratory

Cleaning and Sanitization of Grade D Area.

(Media Destruction Room, Media Preparation Room, Washing area, Media Store Room, Microbiology Office, D Corridor, D Dress Off)

Floor Cleaning & Disinfection:
  • Enter into the specific area for cleaning.
  • Remove the dust particles, papers or any others dirt or dirty materials from the floor with the help of properly cleaned Vacuum Cleaner.
  • Sink the properly cleaned mop into the specific bucket contains detergent solution.
  • Clean the selective area at twice with the help of mop properly.
  • Wash the mop with tap water initially and finally with Purified water.
  • Wipe again the selective surfaces with cleaned wetted mop.
  • Wash the mop to clean it properly with purified water.
  • Sink the mop into the specific bucket containing Dettol/Savlon solution or Chlorine solution
  • Wipe all the selective area with Dettol/Savlon properly.
  • Rinse the mop properly with Purified Water.
  • Wipe all the selective surfaces with the cleaned mop.
  • Use tap water to clean the mop initially and finally clean with purified water
  • Use 70% IPA to sink the mop then dry it.
  • Keep the mop at closed condition in the designated place for the next time use after proper dry.
Walls, glasses, tables, doors, doorknobs, switches:
  • Place the circular cut sponges in bucket containing previous prepared detergent solution.
  • Use sponges previously wetted with detergents solution to wipe down the walls, glasses, tables, doors, doorknobs, etc.
  • Wipe all surfaces with Purified water instead of detergents.
  • Use wetted cloth with 5% Dettol/Savlon solution or 250 to 300 ppm chlorine to wipe down all the surfaces.
  • Wash the cleaning tools with tap water & finally with purified water.
  • Dry it & keep at designated place for the next use.
  • Use detergent once in a week.
  • Use Dettol/Savlon solution and Chlorine solution in alternative week in one after another.
Cleaning and Sanitization of Grade C & B Area:
[Sterility Test Room, Microbial Limit Test Room, C Dress on & Off, B Dress on]
  • Previously mention steps to be Follow for Floor cleaning and Disinfection & Walls, glasses, tables, doors, doorknobs.
  • Wipe all surfaces with 70% IPA wetted sponges.
  • Minimize and control the traffic in the Sterility Test room and Microbial Count Room.
 Cleaning and Sanitization of Laminar Air Flow workstation
  • Remove used flask, used samples or any other dirty materials from the workstation.
  • Wipe whole surface of the workstation with the help of 70% IPA.

Cleaning and Sanitizing at Product Development Laboratory

Cleaning and Sanitization of Grade D Area:
[Dispensing area, manufacturing rooms, In Process check rooms & Material staging and WIP room, D Corridor, D Dress Off]
Floor Cleaning & Disinfection:
  • Enter into the specific area for cleaning.
  • Remove dust particles, papers or any others dirt or dirty materials from the floor with the help of cleaned Vacuum Cleaner.
  • Sink cleaned mop into specific bucket containing detergent solution.
  • Clean all area at twice with the mop appropriately.
  • Wash mop with tap water initially & finally with Purified water.
  • Wipe again all the respective surfaces with cleaned wetted mop.
  • Wash the mop again with purified water.
  • Sink the mop into the specific bucket containing 5% Savlon/Dettol solution.
  • Disinfectant all area with the mop properly.
  • Rinse the mop with purified water.
  • Wipe all surfaces with the cleaned mop.
  • Clean the mop with potable water initially and finally with purified water
  • Keep it at closed condition in the designated place for the next time use.
  • Use 5% Dettol solution for first and third week of the month.
  • Use 5% Savlon solution for second and fourth week of the month.
Walls, glasses, tables, doors, doorknobs, switches:
  • Place sponges in their respective bucket
  • Use wall sponges wetted with detergents solution to wipe down the walls, glasses, tables, doors, doorknobs, switches etc.
  • Use to wipe all of the surfaces with Purified water instead of detergents.
  • Use the towels wetted with 5% Dettol/Savlon solution to wipe down all the surfaces.
  • Take towels in other bucket and sponges to the down up area and leave them there.
  • Wash all the used cleaning tools with tap water & finally with purified water.
  • Dry cleaning tools and keep at designated place for the next time use.
  • Use detergent once in a week.
  • Use 5% Savlon and Dettol solution in alternative week in one after another.

Cleaning and sanitization of others area.                                                                                      

 [Analytical room, E corridor, change rooms, Managers and officers room]

Floor Cleaning & Disinfection:
  • Enter the specific area for cleaning.
  • Remove the dust particles, papers or any others dirt or dirty materials from the floor with the help of  Vacuum Cleaner.
  • Sink the cleaned mop into the specific bucket containing potable water.
  • Clean the designated area at twice with the mop properly.
  • Wash the mop with Purified water.
  • Wipe again all surfaces with properly cleaned wetted mop.
  • Wash with detergent solution twice a week.
  • Wash with 5% Dettol /Savlon solution once a week.
  • Sink the mop into potable water first initially and finally into purified water for cleaning.
  • Keep the mop at closed condition in the designated place for the next time use.
  • Use 5% Dettol solution for first and third week of the month.
  • Use Savlon solution for second and fourth week of the month.
Walls, doors, doorknobs, glasses, tables, switches:
  • Place the sponges in their respective bucket.
  • Use properly wetted sponges with potable water to wipe down the walls, glasses, doors, doorknobs, tables, switches etc.
  • Use to wipe all surfaces with Purified water.
  • Wash all used cleaning tools with potable water and finally with purified water.
  • Dry it and keep at designated place for the next use.
  • Clean twice a week.
  • Use detergent once in a week.

Cleaning and Sanitizing Quality Control Laboratory:

Floor, Wall and Others Area:
  • Empty the dust bins, clean them & keep them at specific place.
  • Clean all tables & reagent racks with the help of dry mopping.
  • Brush the floor of twice daily and then mop with wet mop using liquid soap.
  • Disinfect with prescribed disinfectant solution (2% Savlon & 1% Dettol by weekly rotation). Drain 2% Savlon & 1% Dettol solution through the sink after cleaning & then clean the sink with detergent.
  • Clean doors, windows & glass pans with glass cleaning agent. Sponge may be used for the purpose.
  • In case of spillage occur, stop the activity. Clean the spillage and resume the activity.
  • Clean all the instruments with a cotton duster.
  • Once in a week clean all the fixtures and all the racks in chemical stores with dry mopping.
  • Clean the walls, celling, with vacuum cleaner or with moist duster.
  • After cleaning the area, check the cleanliness of the area and maintain the cleaning record Savlon and Dettol solution in alternative week.
 Cleaning and Sanitizing Record:

Note down cleaning & Sanitization record in Annexure-I, Laboratory Cleaning & Sanitizing Record.

Laboratory Cleaning and Sanitizing of Microbiology, Quality Control, PD Read More »

Microbiological Analysis of Water & its SOP

[Microbiological Analysis of water; this article describes the basic procedure of Microbiological Analysis of water as per different guidelines]

Purpose

Microbiological Analysis of water; To confirm that different type of Water used for different drug processing, cleaning and drinking purpose meets the required Pharmacopoeia & In-house specifications.

Scope

This SOP applies for sampling and analysis of all types of water used in this plant.

Definition/Abbreviation

None

Responsibilities

The roles and responsibility is as follows

Lab Attendant

Sample collection of different types of water.

Executive / Sr. Executive, Microbiology

Verify, Monitoring of Sample collection, analysis of Water, and test preparation of report accordingly.

Asst. Manager/Manager, Microbiology
  • Confirm sampling, analysis, documentation, and application of appropriate technical information.
  • Review of this SOP that the whole procedure is technically informative and in execution condition.
Head of Quality Assurance

Take initiate to the approval of SOP

Procedure

Instructions
  • Disinfect the outer surface of the sampling point with the help of 70% IPA.
  • Wear sterilized latex-free gloves and an appropriate mask. Never forget to wear a beard mask where required.
  • Never open the sample container before & after the collection of a specific sample.
Sample Collection
  • Select the sampling point as per the schedule of the Water Test accordingly.
  • Before sampling sterilized the sampling containers for microbiology test at 1210C for 15 minutes and label it accordingly.
  • Wear appropriate Laboratory garments, gloves, and mask as required.
  • Disinfect the outer surface of the sampling points with the help of 70% IPA.
  • Discharge water for at least 2 minutes for the user points during the collection of sample and 1 minute for a storage tank in the water treatment plant.
  • Collect water from each point at least 200 ml into the sterilized container for microbiology test.
  • Collect the sample as soon as possible.
  • Close the container after sampling and don’t expose the container for microbiology test.
Sample Preservation
  • Samples shall be analyzed as soon as possible after being collected. If it is not possible to test the sample within about 3 hours of collection.
  • The sample may be preserved at refrigerated temperatures (2-80C) for maximum 12 hours to maintain the microbial attributes until analysis.
Test Schedule:

Perform the test as per the following schedule

Microbiological Analysis of water

Microbiological tests are as follows:
Potable/Pretreated Water
  • Perform the test as per Analytical Method
Drinking water
  • Perform the test as per QC Analytical Method
Purified Water
  • Perform the test as per QC Analytical Method
Water for Injection
  • Perform the test as per QC Analytical Method
Report preparation:
  • Report of Potable/ Pretreated/ Drinking water Test Result in Annexure-I,
  • Report of Purified Water Test Result in Annexure-II &
  • Report of Water for Injection in Annexure-IV.
 Distribution of Water Test Result
  • After completion of the analysis, inform the status of water test to a specific department.
  • If any test result exceeds alert level or is out of specification, immediately inform to concerned department Head and engineering department also for corrective measurement.
  • After taking corrective action, Engineering Department shall inform to Microbiology Section for further sample collection.
  • Microbiology Section shall collect the sample from that area to carry out the analysis.
  • After completion of the test, inform about the test result to concerned department after approval of Head Quality Assurance

Microbiological Analysis of water:

 Download All Annexure Here
Potable Water Test Report Annex I
Purified Water Test Report Annex II
Water Test Record (Log Book) Annex III
Water for Injection Test Report Annex IV

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Microbial Examination of Non-Sterile Raw Materials and Products

Microbial Examination of Non-Sterile Raw Materials and Products Purpose

Microbial Examination of Non-Sterile Raw Materials and Products, To confirm that the bacterial & fungal count in the non sterile products & raw materials are within the In-house / Pharmacopoeia specification & free from certain microorganisms indicated in Pharmacopeia.

Scope

This SOP is applicable for microbiological test of Non-sterile Products such such as Oral Liquid, Semi-solid, Solid preparations and Raw Materials in Microbiology Section.

Definitions

Microbial Examination: Microbial examination is designed to determine the microbial contamination in non-sterile   products intended for Oral liquid, Topical Preparations or other non-sterile applications & Raw Materials.

  • CSDA: Casein Soyabean Digest Agar
  • CSDM: Casein Soyabean Digest Medium
  • SDA  : Sabouraud Dextrose Agar
  • SDB  : Sabouraud Dextrose Broth
  • TAMC : Total Aerobic Microbial Count
  • TYMC: Total Yeast & Mould Count

Responsibilities

The roles and responsibility is as follows:

Laboratory Attendant

Preparation Room for Microbiological Test

Microbiologist

Perform the test and incubation and in time proper documentation

Asst. Manager/Manager, Microbiology

Confirm test, incubation, report checking, document preservation and application of precise technical information.

Head of Quality Assurance

Take initiative regarding approval of this SOP

Procedure

Personal Precautions

  • During enter into the test area, wear sterile gloves, Lab coat and eye protection (if necessary).
  • To prevent unauthorized contamination, make sure that all personal ornaments, cell phone are left before entrance into the test room. The use of all type of Cell phone in the test area is strictly prohibited.
  • Don’t move forcefully into the test area. Move always gently.

General Requirements for the test

Glass Apparatus:

  • Pipette 2 ml, 10 ml
  • Sterilized 90 mm Glass Petridish
  • Screw capped Conical Flask 100 ml
  • Screw Capped Test Tube
  • Volumetric Flask 500 ml
  • Volumetric Flask 1000 ml

Media and Reagents:

  • Casein Soyabean Digest Agar(CSDA)
  • Casein Soyabean Digest Broth(CSDB)
  • Cetrimide Agar
  • Mac-Conkey Broth
  • MacConkey Agar
  • Mannitol Salt Agar
  • Meat peptone
  • Neutralized Peptone
  • Rapport Vasiliadis Salmonella Broth
  • Sabouraud Dextrose Agar
  • Xylose Lysine Deoxycholate(XLD) Agar

All of these media can be purchased from commercial available manufacturer.

Others Requirements

  • 70% IPA or ethanol
  • 0.45 µm Membrane Filter
  • Filtration Unit(sterilized filter disk and filtering funnel)
  • Forceps
  • Glass spreader
  • Scissors
  • Surgical Gloves
  • Surgical Cotton

Types of Test for Microbiological Examination

Enumeration Method (TAMC &TYMC)

This test quantify enumeration of mesophilic bacteria & fungi which may grow under aerobic 

Condition.

Test Conditions

  • Wear latex free gloves, Head gear, mask and beard cover [if required], before enter into Test Room
  • Use 70% IPA or ethanol to disinfectant the hands, the outer surface of test sample, LAF workstation with before start test.
  • Perform the test under LAF to avoid contamination.
  • Monitor the test area microbiologically with the help of Microbial Air Sampler at each working day.

Culture Media Preparation

  • Prepare the different culture media as per specific requirements.
  • Weigh the exact amount stated in the manufacturer label into right flask.
  • Bring to boil completely to dissolve the media properly.
  • Sterilize at 1210C for 15 minutes or as directed by the Manufacturer label.
  • Store the prepared culture media in air tight flask properly at controlled environment.
  • Store the prepared agar media at 2-80C.
  • Preserve the dehydrated culture media up to expiry date.
  • Never use the expired culture media.
  • Use the agar media when the temperature reduce near at 450C & cool in case of the broth media.

Stock Buffer Solution

  • Place 34 g of Potassium Dihydrogen Phosphate[KH2PO4] in a 1000 ml volumetric flask
  • Dissolve in 500 ml of purified water, adjust to pH [7.2 ± 0.2] & dilute to 1000ml with purified water.
  • Dispense  90 ml into  each screw capped flask 
  • Sterilize at 1210C for 15 minutes.
  • Store the prepared buffer at 2-80C for a validated period.

Glassware Cleaning & Sterilization

  • Initially clean all glassware by 1% detergent & then rinse with sufficient tap water.
  • Finally Rinse with sufficient Purified Water to remove the residual content of detergent.
  • Sterilize glassware at 2000C for 1 hour.

Testing of Products

Sample Size

  • Collect 10 g or 10 ml of the products to be taken. 10 containers of the products from a batch.
  • Collect the amount is not less than the amount present in 10 dosage units or 10 g or 10 ml of the respective product,  if amount per dosage unit is less than or equal to 1 mg.
  • Take 1% of the batch size when batch size is less than 1000 ml or 1000 gm.
  • Take 2 units or 1 units if the batch size is less than 100.

Types of Method

  • Membrane Filtration
  • Most Probable Number Method
  • Pour Plate Method
  • Surface spread Method

Membrane Filtration Method

  • Prepare sample as per Method Suitability.
  • Filter the sample through 0.45 µm & transfer the filter to the surface of CSDA for bacterial count and SDA[Sabouraud Dextrose Agar] for fungal count.
  • Incubate CSDA[Casein Soyabean Digest Agar] at [30-35]0C for 3-5 days & at [20-25]0C for 5-7 days.
  • After incubation, calculate the number of the cfu per gm or ml of the product.

Negative Control

Use diluents in place of test preparations. There must be no sign of growth in negative control. If found any sign of growth in negative control, the test must be invalid and repeat the whole test accordingly.

Pour Plate Method

  • Prepare the sample as per the Method Suitability
  • Pour 1 ml of prepared sample into the four 90 mm petridish, Add 15-20 ml CSDA[Casein Soyabean Digest Agar] into two plate & SDA into the others two plate.
  • Allow to solidify & invert all plates.
  • Incubate CSDA at [30-35]0C for 3-5 days and at [20-25]0C for 5-7 days.
  • After incubation, calculate the number of the cfu per gm or ml of the product.

Negative Control

Use diluents in place of test preparations. There must be no sign of growth in negative control. If found any sign of growth in negative control, the test must be invalid and repeat the whole test accordingly.

Surface spread Method

  • Prepare the sample as per Method Suitability.
  • Spread not less than 0.1 ml of sample on the surface of two CSDA[Casein Soyabean Digest Agar]  and two SDA[Sabouraud Dextrose Agar] Plate.
  • Dry all plates at Laminar Air Flow.
  • Incubate the CSDA at [20-25]0C for 5-7 days and at [30-35]0C for 3-5 days.
  • After incubation, calculate the number of the cfu per gm or ml of the product.

Negative Control

Use diluents in place of test preparations. There must be no sign of growth in negative control. If found any sign of growth in negative control, the test must be invalid and repeat the whole test accordingly.

Interpretation of the results

Count as Total Yeast/ Mould Count (TYMC) on SDA plate and Total Aerobic Microbial Count(TAMC) in CSDA plate and The acceptable criterion for microbiological quality is prescribed as :

  • 101 cfu : maximum acceptable count =20
  • 102 cfu : maximum acceptable count =200
  • 103 cfu : maximum acceptable count =2000

Declaration

  • The Material/product is passed when the observed count is less than specified count of that Material/product.
  • The Material/product is failed if the observed count is greater than specified count of that Material/product.
  • In that case, repeat the test, if the count is greater than specified count, the product is failed.

Test for Specified Microorganisms

Suitability of Test Method

Cary out the test in presence of the product. Add each test strain distinctly not more than 100 cfu at the time of product mixing with the culture media.The test will be suitable if found growth of the specific microorganism. The test will not suitable if no growth found the specific microorganism. In thatcase, add any neutralizer or increase the dilution for removal any inhibition of product.

Testing of Products

Test for E. coli

  • Add 10 g or 10 ml of test sample to the 90 ml of Casein Soyabean Digest Medium. Incubate at [30-35]0C for 18-24 hours.
  • Shake the container then transfer 1 ml of CSDM to the 100 ml of MacConkey Broth. Incubate at [42-44]0C for 24 hours.
  • Sub-culture on MacConkey Agar plate from MacConkey broth. Incubate at [30-35]0C for 18-72 hours.
  • The product complies with the test for E. coli if no red colonies are present with precipitated zone and the biochemical tests found negative[-ve].

Test for Salmonella

  • Add 10 g or 10 ml of test sample to the 90 ml of Casein Soyabean Digest Medium. Incubate at [30-35]0C for 18-24 hours.
  • Shake the container; transfer 0.1 ml of CSDM to 10 ml of RVS [Rappaport Vassiliadis Salmonella] Broth. Incubate at [30-35]0C hours for 18-24 hours.
  • Sub-culture on XLD [Xylose Lysine Deoxycholate] Agar plate from RVS [Rappaport Vassiliadis Salmonella] Broth . Incubate at [30-35]0C for 18-48 hours.
  • The product complies with the test for Salmonella if no red colonies are present with or without black centres and the biochemical tests are negative[-ve].

Test for Pseudomonas aeruginosa

  • Add 10 g or 10 ml of test sample to the 90 ml of Casein Soyabean Digest Medium. Incubate at [30-35]0C for 18-24 hours.
  • Sub-culture on Cetrimide Agar plate from CSDM [Casein Soyabean Digest Medium]. Incubate at [30-35]0C for 18-72 hours.
  • The product complies with the test for Ps. aeruginosa if no bluish green colonies are present and the biochemical tests are negative[-ve].

Test for C. albicans

  • Add 10 g or 10 ml of test sample to 90 ml of SDB [Soubaurad Dextrose Broth]. Incubate at [30-35]0C for 3-5 days.
  • Sub-culture on SDA[Soubaurad Dextrose Agar] plate from [Soubaurad Dextrose Broth]. Incubate at 30-350C for 24-48 hours.
  • The product complies with the test for C. albicans if no white colonies are present and the   biochemical tests are negative[-ve].

Test Report Preparation

  • Report the result in Microbial Count Report of Non-sterile RM, Annexure-I.
  • Report the result in Microbial Count Report of Non-sterile Products, Annexure-II.

This is all about the Microbial Examination of Non-Sterile Raw Materials and Products and based on this information you can generate a SOP for Microbial Examination of Non-Sterile Raw Materials and Products.

Download all Annexure

Annexure I Microbial Count Report of Non-Sterile Raw Materials

Annexure II Microbial Count Report of Non-Sterile Products

Annexure III Non Sterile Raw Materials Log book

Annexure IV Non Sterile Products Log book

Microbial Examination of Non-Sterile Raw Materials and Products Read More »

Growth Promotion Test Procedure of Culture Media & its SOP

Growth Promotion Test Purpose:

Growth Promotion Test, To verify that the culture media is capable to growth in order to use in Microbiology Test specified in Pharmacopoeia.

Scope of Growth Promotion Test:

This SOP applies for verification of the effectiveness of culture media which is used in Microbiology Laboratory at XX Pharmaceuticals Limited.

Definitions/Abbreviation :

CFU      : Colony Forming Unit

CSDA   : Casein Soyabean Digest Agar

CSDB   : Casein Soyabean Digest Broth

GPT      : Growth Promotion Test

SDA     : Sabouraud Dextrose Agar

SDB     : Sabouraud Dextrose Broth

TAMC   : Total Aerobic Microbial Count

TYMC   : Total Yeast & Mould Count

Responsibilities:

The roles and responsibility is summarized as follows:

Executive, Microbiology

To execute Inoculation, incubation of Culture media and plate count of Growth Promotion Test.

Assistant Manager/Manager, Microbiology

To ensure Growth Promotion Test, documentation and application of sound technical information.

Head of Quality Assurance

Approval of this SOP

Procedure:

Note:

  • Don’t move forcefully into the test area. Move always gently.
  • Disinfect all apparatus using 70% IPA before transfer into the Laminar Air Flow.
  • When enter into test area, wear sterile latex free gloves, lab coat/apron and eye protection (when required).
  • To prevent the unauthorized contamination, make sure that all personal ornaments, all type of cellular phone are left before enter into the test room.

General Requirement :

Glass Apparatus :

  • Pipette 2 ml, 10 ml
  • Screw Capped Test Tube
  • Sterilized 90 mm Glass Petridish
  • Screw capped Conical Flask 100 ml
  • Volumetric Flask 500 ml
  • Volumetric Flask 1000 ml

Media and Reagents:

  • Meat peptone
  • Neutralized Peptone
  • Selected Media

Others Requirements:

  • 70% IPA or ethanol
  • 0.45 µm Membrane Filter
  • Forceps
  • Filtration Unit( sterilized filter disk and filtering funnel)
  • Glass spreader
  • Scissors
  • Surgical Gloves
  • Surgical Cotton

Test Conditions:

  • Monitoring the testing area using by Microbial Air Sampler during working day.
  • Perform test under LAF to avoid any type contamination.

Culture Media Preparation:

  • Prepare different culture media  as per specific requirement
  • Weigh the amount declared in the manufacturer label into the appropriate flask.
  • Bring to boil completely to dissolve media.
  • Sterilize at 1210C for 15 minutes or as per Manufacturer declaration mention on the label.
  • Store the prepared culture media in air tight flask controlled room temperature at controlled environment
  • Store prepared agar media at (2-8)0
  • Preserve the dehydrated culture media up to its expiry date.
  • Never use the expired culture media.
  • Use agar media when the temperature reduce near at 450C and cool in case of broth media.

Stock Buffer Solution:

  • Place 34 g of Potassium Dihydrogen Phosphate[KH2PO4] in the 1000 ml volumetric flask
  • Dissolve in 500 ml of Purified Water then adjust to pH (7.2 ± 0.2) and dilute to make 1000ml with Purified Water.
  • Dispense 90 ml into each screw capped flask [5 or more flask required]. 
  • Sterilize at 1210C for 15 minutes.
  • Keep the prepared buffer solution at (2-80C) for a validated period.

Glassware Cleaning & Sterilization:

  • First of all clean all glassware with 1% detergent and then rinse with sufficient tap water.
  • Finally Rinse with sufficient Purified Water to remove the residual content of detergent.
  • Sterilize all glassware with Dry Heat Sterilizer at 2000C for 1 hour.

General Procedures

Growth Promotion Test (GPT) of General Media

  • Carry out Growth Promotion Test for each prepared culture media.
  • Prepare standardized suspension for the different test strains as mentioned in Table 1
  • Use sterile Buffer Sodium Chloride [NaCl]-Peptone solution where pH 7.0 or Phosphate Buffer which pH 7.2 as respective diluents.
  • Use the standard test strains are not more than 5 passages from original master seed lot.
  • During preparation of Aspergillus brasiliensis suspension, add 0.5% Polysorbate 80 to the buffer solution.
  • Use the suspension within 24 hours when preserve at (2-8)0C otherwise use within 2 hours.
  • Freshly prepare the Bacillus subtilis and A. brasiliensis suspension and  store at (2-8)0C for validated period, then dilute it for use.
  • Inoculate distinctly 100 cfu of each microorganism to 10 ml of each liquid media & follow spread plate method for solid media as mention in Table 1.
  • Incubate the medium for fungi at (20-25)0C for 5 days and for bacteria at (30-35)0C for 3 days.
Growth Promotion Test

Interpretation of Results:

  • Liquid media is suitable for use, if growth found, then it is clearly on each media.
  • Solid media is suitable when count is not greater than 2 from the calculated value of the standardized value.

Inoculation and Dilution:

  • Add the sufficient volume of suspension of inoculums to the sample to maintain not more than 100 cfu
  • Add inoculums suspension not more than 1% of the diluted product.
  • Prepare lowest possible dilution for tolerable microbial recovery of sample
  • When sample contains any antimicrobial properties add the neutralizer to remove Interfering factor.
  • When growth is inhibited then increase the use of diluents or membrane filtration or combination of all   above.
  • Add (20-25) ml of SCDA[Soyabean Casein Digest Agar] & SDA[Sabouraud Dextrose Agar] to 90 mm diameter petridish at least duplicate.
  • Incubate the medium for bacteria at 30-350C for 3 days and the medium for fungi at 20-250C      for 5 days.

Interpretation of  Results :

  • Liquid media is suitable for use, if growth found, then it is clearly on each media.
  • Solid media is suitable when count is not greater than 2 from the calculated value of the standardized value.
  • Growth obtained must not be differing by a factor greater than 2 from the calculated value for standardized inoculums for Solid Media, For freshly prepared inoculums, growth of the micro-organisms comparable to that previously obtained with a previously tested and approved batch of medium occurs.

Growth Promotion Test of Selective Media:

Growth Promotion & Inhibitory Test :

  • Perform this test for each prepared media.
  • Inoculate the each media not more than 100 cfu microorganisms as per Table 2
  • Perform surface-spread method for solid media
  • Incubate the media as per specified in that microorganisms.

Interpretation of Result :

  • The media is suitable for use if growth found clearly in liquid media and found the specific  colony characteristics on solid media.
  • Inhibitory test is failed when no growth found occurs the specific colony.
growth promotion test

Test for E. coli :

  • Add the specific microorganism to 100 ml of CSDM. Incubate at 30-350C for 18-24 hours.
  • Shake the container, transfer 1 ml of SCDA[Soyabean Casein Digest Agar] to 100 ml of MacConkey Broth. Incubate at [42-44]0C for 24 hours.
  • Subculture on MacConkey Agar plate from MacConkey broth. Incubate at 30-350C for 18-72 hours.
  • GPT of that culture media complies with the test for E. coli if the red colonies are present with precipitated zone & the biochemical tests are negative[-ve].

Test for Salmonella

  • Add the specific microorganism in 100 ml of CSDM. Incubate at 30-350C for [18-24] hours.
  • Shake the container, transfer 0.1 ml of CSDM to 10 ml of Rappaport Vassiliadis Salmonella (RVS) Broth. Incubate at 30-350C hours for 18-24 hours.
  • Subculture on Xylose Lysine Deoxycholate (XLD) Agar plate from Rappaport Vassiliadis Salmonella (RVS) Broth. Incubate at [30-35]0C for [18-48] hours.
  • GPT of that culture media complies for Salmonella if no red colonies are present with or without black centres and the biochemical tests are negative.

Test for Pseudomonas aeruginosa

  • Add the specific microorganism to 100 ml of CSDM. Incubate at 30-350C for 18-24 hours.
  • Subculture on the Cetrimide Agar plate from CSDM. Incubate it at 30-350C for 18-72 hours.
  • GPT of that culture media complies with the test for Ps. aeruginosa if no bluish green  colonies are present & the biochemical tests are negative[-ve].

Test for staphylococcus aureus

  • Add the specific microorganism into 100 ml of CSDM. Incubate it at (30-35)0C for 18-24 hours.
  • Sub-culture on Mannitol Salt Agar plate from CSDM. Incubate at (30-35)0C for 18-72 hours.
  • GPT of that culture media complies with the test for St. aureus if no yellow/white colonies        
  • Surrounded yellow zone are present and the biochemical tests are negative.

Test for Candida albicans

  • Add specific microorganism to 100 ml of Soubaurad Dextrose Broth(SDB). Incubate at (30-35)0C for (3-5) days.
  • Subculture on Soubaurad Dextrose Agar[SDA] plate from SDB[Soubaurad Dextrose Broth]. Incubate at [30-35]0C for [24-48] hours.
  • GPT of that culture media complies with the test for C. albicans if no white colonies are present and the biochemical tests are negative[-ve].

Growth Promotion Test Report Preparation:

  • Prepare Report in Growth Promotion Test Report of General Culture Media, Annexure-I & Growth Promotion Test Report of Selective Culture Media, Annexure-II.

Download: All Annexure

Annexure-I Growth Promotion Test of General Culture Media

Annexure-II Growth Promotion Test of Selective Culture Media

Growth Promotion Test Procedure of Culture Media & its SOP Read More »

Culture Media preparation in Microbiology Laboratory & its SOP

Culture Media Purpose

Culture Media, To make the culture media for the development of microorganisms in the microbiological test of raw materials, In-process sample & finished products.

Culture Media Scope

This designated SOP is applicable for the preparation of Culture Media in Microbiology Laboratory at XX Pharmaceuticals Limited.

Definitions/Abbreviation: 

Culture Media: The Culture media is a liquid or gel designed to support growth of microorganisms or cells  or small plants.  There are different type of media for growing different type of cells. 

There are two major types of growth media: those used for cell culture, which use specific cell types derived from plants or animals, and microbiological culture, which are used for growing microorganisms, such as bacteria or yeast.

Responsibilities:

The roles and responsibilities are as follows:

Officer/Sr. Officer, Microbiology

To follow the instructions of the described procedure accordingly.

Asst. Manager/Manager, Microbiology

  • Ensure that the procedure is kept up to date.
  • Ensure right personnel from the section are trained on this specific procedure.
  • Ensure the media preparation, sterilization, requisition, maintain accurate storage & proper documentation.
  • To Confirm that this SOP is technically sound and reflects the required working practices as current practices.

Head of Quality Assurance

  • Approval of SOP
  • To ensure the overall implementation of the SOP

Procedure

Instructions

Dehydrated media are hygroscopic & are sensitive to light, heat and moisture. They are adversely affected by extreme changes in temperature e.g. hot/ cold cycling temperatures which may occur between day and night laboratory temperatures in winter season.

Condition of Media Preparation:

  • Take clean & dry flask as per required volume.
  • Wear appropriate Laboratory garments, gloves and mask.
  • Wear safety goggles during selection of hazardous media.

Storage Condition of Dehydrated Media:

  • Mention receipt date on the label when enter into laboratory.
  • Store as per directions on the label; typically below 250C in a dry area, away from direct sunlight,  autoclaves, drying ovens or other heat sources, Where indicated store at (2-8)0C.
  • Check expiry date on the specific label, some media have suggestively shorter shelf life than others.
  • Use/maintain stock in lot/batch number order. Maintain FIFO [First In First Out], FEFO [First Expiry First Out].
  • Do not open a new bottle until the previous bottle has been emptied. Ensure date with label on the supplied container when it first opened.
  • After intended use, ensure the container is tightly closed and store it into the designated storage area.
  • Collect/procure/order the medium in an appropriate size of container and in a quantity which harmonies to normal use requirements.
  • A medium in a large container which has been opened many times will deteriorate on storage. Discard the medium if the powder is not free flowing, if the colour has changed or if it   appears abnormal in any way.
  • Temperature of media storage room/facility/area/location should be monitored through min./max. thermometer and limit shall be followed as per the media storage requirements.
  • List of media having designated storage condition and specific pH limit shall be prepared as per Annexure-II and shall be displayed near media storage facilities.

pH Check:

Check pH of the specific medium before sterilization with calibrated pH meter. If required adjust the pH with the help of 1N or 0.1N NaOH and 1N or 0.1N HCl solutions.

Culture Media Preparation:

  • Select the media as per specific requirements.
  • Read the instructions on the label very carefully before preparation of the specific media.
  • Weigh the media according to the instructions of the manufacturer of the supplied media.
  • Close the media container tightly just after weighing in order to avoid the moisture acquisition.
  • Reconstitute the media with purified water and boil it appropriately until entirely dissolve.
  • Distribute the reconstituted media into clean and dry flask as per requirements.
  • Cap the flask using cotton plug or screw cap appropriately.
  • Transfer the media flask into the detest room for use if instructed on the label as “DO NOT AUTOCLAVE” the media.

Sterilization:

  • Place all prepared media into the autoclave.
  • Sterilize the media at 1210C for 15 minutes.
  • Wait until completion of cycle, and collect sterilized media from the autoclave when the chamber temperature reduce at 600C.

Storage of Sterilized culture Media:

  • After completion of autoclaving activities, transfer all flasks containing the broth media to the test room for use.
  • Store the agar media at the warming condition (500C) into autoclave until use.
  • Do not keep the prepared media for more than two weeks [14 days].
  • Keep the prepared agar plate at (2-8)0C into the refrigerator for not more than two weeks.

Handling of Sterilized culture Media:

  • Ensure the aseptic condition during handle of sterilized media.
  • Do not de-cap or expose the sterilized media outside Laminar Air Flow or Bio-Safety Cabinet.

Record Keeping:

Keep in practice to Maintain Register for Media Preparation Record, Annexure-I and Annexure-II to keep record for list of media with storage condition and pH limit.

List of Annexure: Download Here

Annexure I Register of Media Preparation

Annexure II List of Media with storage condition and pH Limit

Culture Media preparation in Microbiology Laboratory & its SOP Read More »

Bacterial Endotoxins Test, how to perform it easy way?

Bacterial Endotoxins Test (BET) is use to determine the quantity of bacterial endotoxins which present in the cell wall of the gram negative bacteria. Medical devices which are subject to contact[directly/indirectly] with the lymphatic system, cardiovascular system or cerebrospinal fluid must be undergo Bacterial Endotoxins Test (BET) as part of the lot release testing.

Bacterial Endotoxins Test (BET) is mandatory for the Injectable pharmaceutical products. The validated water system which is subject to routine monitoring and the starting/incoming materials must be ensure that the final product doesn’t effect by its endotoxins. The BET is also known as LAL[Limulus Amebocyte Lysate] Test and also known as Pyrogen test due to bacterial endotoxins can cause a fever in mammals, including humans. Don’t messed up with rabbit pyrogen test which is mentioned in USP chapter <151>.

Also read the following guidance for better understanding- for Industry Pyrogen and Endotoxins

  • ANSI/AAMI ST72:2011
  • FDA Guidance
  • EP 2.6.14
  • JP 4.01
  • USP Chapter <85>
  • USP Chapter <161>

In pharmaceutical industry and the industry which are manufacturing sterile products/products label claim itself sterile to its intended use must be pyrogen free and BET test must be done before release of the batch/lot to the market. Sterile pharmaceutical products and Water for injections are undergo BET in a pharmaceutical firm using gel clot method.

BET is an in-vitro test which is used to seek the endotoxins presence in the specific test sample/products. Endotoxins are frequently known as Pyrogen which are mainly produced by gram-negative bacteria. The main principle of BET makes it the utmost sensitive test that one can use to detect and quantify endotoxins, toxins which are notably known for causing fever in human.

During purification, production or packaging stages of Pharmaceutical products, it can be contaminated and BET must be perform before using its as sterile parenteral solutions. To identify the presence of endotoxins, add the sample to the Lysate, an enzyme found from horse shoe crab which hemolymph cells is mainly responsible to produce Lysate. The main principle of the BET is physiological reaction between the amoebocytes and endotoxins. The amoebocytes are fond on the blood of horse shoe crabs.

Amoebocytes found in the horse shoe crabs provide protection mechanism against pathogens. The Amoebocytes contains granules possess clotting factor which is generally released when encountered by the endotoxin causing coagulation. So this is very basic that the main mechanism of BET is physiologic effect between coagulating factor and endotoxins.

At the time of BET, the combination of endotoxins and calcium, a preclotting enzyme is typically activated which play a major role to catalyze the transformation of procoagulogen into a unit generally made of polypeptide. It is marked as coagulogen, its link up by a disulfide bond form gel-clot. With the help of a spectrophotometry, the formed precipitate subject to measure to identify if there are endotoxins in a test sample.

Types of Bacterial Endotoxins Test (BET)

  • Gel clot technique
  • Turbidimetric method
  • Chromogenic method

There are three endotoxin detection methods are available but among these methods, gel clot technique is widely used to detect the Bacterial Endotoxins which form gel that can be easily identified. Another method is known as turbidimetric method where the amount of endotoxins are measured based on the turbidity.

The selected sample introduce into a specific solution contains endogenous substrate, cleaved upon introduction of the endotoxin containing sample and generate turbidity. Intensity of the turbidity indicate the presence of endotoxin otherwise absence. The third and last method is chromogenic method which produce color. The selected sample is introduced into a solution contains synthetic complex made of peptide-chromo-gen. If the solution develop color then it indicate the presence of endotoxin to the suspected solution.

This method is very simple and time saving method. Generally 1 hour is required to determine the test result of the selected solution and more efficient compare to another method and very useful in pharmaceutical industry avoid using of animal for the similar purpose.

Procedure for Bacterial Endotoxin Test

Precautions:

Avoid touch contamination of closures.

Dehydrated endotoxin, LAL reagent and LAL water stored in a refrigerator in the temperature of (2-8)0C.

Use Endotoxin free apparatus during testing.

Preparation of Lysate:

Lysate must be reconstituted just before use by addition of the designated amount of LAL Reagent Water with the help of pipetting it directly into the vial after removing the stopper. Accumulate Lyophilized LAL powder into the bottom portion of the vial applying slight tapping on the hard surface.

Wear safety goggles if hazardous media is selected. Elude touch contamination of closures. Swirl gently but thoroughly for at 30 seconds until dissolve. Avoid any type of shaking/vibration.

Preparation of standard Endotoxin:

CSE [Control Standard Endotoxin] is an endotoxin preparation that has been standardized against the USP RSE [Reference Standard Endotoxin].Constitute the entire contents of 1 vial of the CSE with 5 ml of LAL water, mix spasmodically of 5 minutes, with the help of vortex mixture, and use this concentration to make appropriate serial dilutions.

Preserve the concentration in a refrigerator for making subsequent dilutions for 14 days only. Mix robustly with the help of vortex mixture, only for 3 minutes before use. Mix each dilution for 30 seconds before proceeding to make the next/another dilutions. Never/ever store the dilutions.

Determination of Maximum Valid Dilution (MVD):

Maximum Valid Dilution is maximum allowable dilution of a specimen/sample at which the Endotoxin Limit can be determined.

MVD applies to injection or to solution for parenteral administration in the form constituted or dilute for administration or wherever applicable, to the extent of drug by weight if the volume of dosage forms for administration could be varied.

General equation for the determination of MVD is defined as:

MVD = Endotoxin Limit × Concentration of sample solution and/ Sensitivity of reagent

When the sample under test comply with the test at a dilution less than Maximum Valid Dilution, repeat the test using greater dilution but not exceeding the MVD. The use of more sensitive Lysate permits a greater dilution of sample to be inspected.

Confirmation of labeled LAL reagent sensitivity:

Labeled sensitivity of LAL Reagent to be confirm using at least 1 vial of LAL Reagent lot. Prepare a series of two fold dilutions of the control standard endotoxin in LAL reagent water to provide concentration at 2λ, λ, 0.5 λ, 0.25 λ. Accomplish the test on four standard concentrations in quadruplicate and include the negative control.

Lysate sensitivity Test confirmation of to be carried out when a new batch of LAL Reagent is used. Mix the volume of LAL Reagent with an equal volume (such as 0.1 ml aliquots) of one of the standard solution in each test tube. Incubate reaction mixture for a constant period according to directions provided by the LAL manufacturer (usually 37±1ºC for 60±2 minutes), avoiding vibration, into incubator.

To verify/identify/test the integrity of gel, take each tube in turn directly from the incubator & invert it through about 180º in one smooth motion. If a firm/fixed gel formed which remains in place upon inversion, record the result as a positive. Mark result is negative if an intact gel is not formed/found. The test will not declare valid unless the lowest concentration of the standard solutions shows negative results in all replica test.

SolutionEndotoxin concentration/solution to which Endotoxin is addedNumber of Replicates
ANone / Sample solution2
B2λ / Sample solution2
C 2λ / Water of BET2
D None / LAL Reagent Water2

Solution A: A sample solution of the preparation under test that is free of detectable Endotoxin

Solution B: Test for interference.

Solution C: Controlled for labeled LAL reagent Sensitivity.

Solution D: Negative control of LAL Reagent water.

Gel Clot Limit Testing:

Depyrogenate all related glassware & heat-stable materials in a hot-air oven using validated process at the time and temperature setting are 30 minutes at 250ºC respectively. Plastic apparatus like micro-plates & pipette tips for automatic pipette use only that which has been shown to be free of detectable Endotoxin and do not to interfere with test result. Perform the inhibition test on the sample dilution at dilution.

pH of the test mixture of the specimen & the LAL Reagent is in the range 6.0 to 8.0 The pH may be adjusted by the addition of sterile, Endotoxin free Sodium Hydroxide[NaOH] or Hydrochloride Acid[HCl] or Suitable Buffers to the Specimen before testing. Mix a volume of the LAL reagent with the equal volume [such as 0.1 ml aliquots] of one standard solution in each of (10 X 75) mm test tube.

Incubate reaction mixture for a constant period according to directions provided by the LAL manufacturer [usually 37±1ºC for 60±2 minutes, avoiding vibration, into incubator. To test/identify/verify the integrity of the gel, take each tube in turn directly from the incubator and invert it through about 180º in one smooth motion.

If a firm gel has formed that remains in place upon inversion, record the result as a positive. A result is negative if an intact gel is not formed. Calculate the detected Endotoxin, through used dilution factor and used LAL reagent [Lysate Sensitivity]. Generate Report the test result.

Download all annexure from below the link:

Annexure-I Endotoxin Test Report

Annexure-II Lysate Sensitivity Test Record

Annexure-III Endotoxin Test Record Logbook

Bacterial Endotoxins Test, how to perform it easy way? Read More »

Sterility Test, how to perform Sterility Test in the best way?

Sterility Test

Sterility test is the basic requirements for the products claim it is sterile for its intended use. This is the core requirements to ensure the sterile status of the products which never contain the viable microorganism at the time of use to the patients or must confirm before released for sales.

Sterility testing need to be as precise as possible due to its critical point of use such as pharmaceutical products, tissue materials, blood products, serum preparations, vaccine preparation, Insulin preparations, powder for injections etc. and the other products which are claim to be sterile or free from viable microorganisms.

Various types of firm, food factory, pharmaceutical industry, beverage manufacturers, and medical device manufacturer’s etc. company use Sterility testing procedures which company deal with the sterile products and this is mandatory for them. Generally, a microbiologist or a group of microbiologists are involve to perform the sterility test based on company work flow.

A Consistent sterility testing is the core to the develop or validate a specific product or procedure. Continuous robust test method is mandatory get the accurate test result repeatedly. A robust quality infrastructure is required to support the biopharmaceutical, pharmaceutical, and medical device industries.

Direct Inoculation and Membrane Filtration Methods

Sterility testing is required to ensure viable contaminating microorganisms are not evident in a product. This testing is conducted by direct inoculation or membrane filtration methods and can be performed in an isolator or cleanroom environment.

Sterility Testing Techniques

There are several sterility Testing are available-

Recommended Sterility Test: Two Types

  • Direct inoculation
  • Membrane filtration

Additional Test: Two Types

  • Bacteriostasis/fungistasis testing–b/f testing
  • Vaporized Hydrogen Peroxide (VHP) ingress testing

Direct Inoculation

Here two types of media are used to directly inoculate the test article for the determination of the both aerobic and anaerobic microorganisms. The both media are for 14 day from the start of the test day and sporadic observations as well as final/end day observations are done to check the any type of evidence of microbial contamination.

A suitable volume of growth media is used to inoculate small volume of sample which is directly collect from sample container by applying aseptic technique then it incubate for 14 days. Direct Inoculation Sterility Testing has some significant limitations. The sensitivity is low for the test as small volume of a full container is inoculate to the respective culture media. At the starting of inoculation, if the sample appears cloudy or turbid then this very challenging to detect the turbidity and the end of the test period for the microbial growth.

Membrane Filtration Sterility Testing

Here the simultaneous filtration of test sample and standard preparation perform through two membrane filters and the samples are subsequently incubated for 14 days from the start of the test day, and finally check/determine the visibility of the microorganisms both aerobic and anaerobic.

The filterable pharmaceuticals product are subject to Membrane Filtration Sterility Testing which have been described in EU Pharmacopoeia < 2.6.1>, USP <71> & JP Pharmacopoeia <4.06>. To perform the test 0.45 µm membrane filter is used to pass the sample, then culture medium is added for incubation. The sensitivity of the test is more precise as the whole or composite sample is passed through the filter. Another best opportunity of the Membrane Filtration Sterility Testing is, its rinse away components present in the sample which may cause the turbidity or inhibit growth as for example preservatives or antibiotics.

Bacteriostasis/Fungistasis Testing–B/F Testing

Bacteriostasis/fungistasis testing is perform in conjunction with the sterility test evaluate whether or not the test article is inhibitory to the growth of the different microorganisms. To evaluate the sterility result Bacteriostasis/fungistasis test is essential to ensure that test article don’t contain any antimicrobial properties and it don’t inhibit the detection of microorganism at sterility test.

Vaporized Hydrogen Peroxide (VHP) Ingress Testing

An isolator required to perform the Vaporized Hydrogen Peroxide (VHP) Ingress Testing which undergo undergoes VHP decontamination. This assay assesses if VHP enter to the test article is apparent that may affect the validity of the result.

What is Sterility Test USP <71>?

Sterility test USP <71> is the chapter of USP[United States Pharmacopeia] which represents how the sterility test to be perform, and the detail description, methodology and how the product to be tested based on the fill volume and sample size.

Media use in sterility testing

The sterility testing of the all product subject to sterile require two types of media which to be cultured in separate two media. In sterility testing, two types of culture media are used to promote the growth of residual anaerobes, as well as aerobes and fungi.

FTM[Fluid Thioglycolate Medium] and SCDM[Soybean Casein Digest Medium], these two type of media are used use to culture anaerobic and some aerobic bacteria and fungi.

Generally FTM is use for culture of anaerobic and some aerobic bacteria on the other hand, SCDM is use for fungi and aerobic bacteria. Before examination the samples are incubated for 14 days at 32.5°C and 22.5°C. Media must be turbidity free. Presence of turbidity in the respective culture media subject to growth of microorganism and it must be investigate.

Sterility testing methods for medical devices

For medical devices testing, direct transfer sterility testing is recommended. The respective devices are tested is in direct contact with the designated test media during the incubation period where microorganism is growing on or in the device to be check. Transfusion and infusion assemblies related products which contain fluid pathway declared sterile then product flush sterility testing is preferred for this type of product. Here a rinsing fluid is used to flush the product lumen then the elute is passed through the membrane filter and after that it place on the suitable media for incubation for 14 days.

sterility test

Sterility Testing Procedure

Precautions:

Be assured of strict devotion with aseptic technique and no occurrence of secondary contamination in every step of the test. Traffic in the LF workbench should be reduce and well-ordered. Use cellulose acetate membrane filters when strongly alcoholic solutions are subject to filter. If the solution being tested has antimicrobial properties, rinse the membrane at least three times with sterile dilution fluid.

Avoid piercing/ splitting of HEPA filter with liquid and spraying of solutions on the workbench. Use single syringe for single batch or test and avoid touch contamination of the needle and plunger of the syringes. All rubber stoppers of vials and neck of ampoules should be out of hand touch as hands are clean but not sterile. Check all the media for clarity as well as sterility before use. Perform positive control/growth promotion test in another separate area from sterility test area under Bio-safety Cabinet.

Media and Diluents:

Tryptone Soya Broth (TSB) 

Fluid Thioglycollate Medium (FTM). [When medium is stored, store at a temperature between 2ºC and 25 ºC in a sterile, air tight container. If more than upper one third of the medium has acquired a pink color, then to remove the pink color, the medium may be restored once by heating the containers in a water bath until the pink color vanishes and by cooling quickly.] USP Diluting Fluid A/rinse solution (1g/L peptone water/Sterile water for injection)

USP Diluting Fluid D (To each Liter of Fluid A/rinse solution add 1 mL of polysorbate 80, adjust to a pH of 7.1± 0.2). For Cephalosporin/Penicillin, add a quantity of sterile β lactamase, adequate to deactivate any residual antibiotic activity on the membranes after the solution of the test specimen has been filtered. Filtered 70% IPA (Isopropyl Alcohol).

 Prepare these dehydrated mediums and ensure effectiveness of the media before, or in parallel, with the sterility test on the product subject to be examined. Growth promotion test of medium should be justified.

Method of Testing:

  • Membrane filtration
  • Direct inoculation

Criteria of membrane filter:

  • Filter I: Cellulose Nitrate Filter[CNF] for aqueous, oily and weakly alcoholic solutions and Filter II: Cellulose Acetate Filter[CAF] for strongly alcoholic solutions.
  • Diameter of membrane filter: 47 mm
  • Pore size of the membrane filter: Not greater than 0.45 µm.

Test sample:

Sterility test is a destructive test [You can’t return the test sample] and it is impossible to test every single item for sterility. Sample for testing should be representative of the batch, which ensures that the results of the tests are substantial. Arbitrary samples are optimally selected every Lth unit, where L = the total units in the batch per number of sample required.

The following number of samples should be used in sterility test described in Table – 1 and Table -2.When the test samples are turbid and is impossible to filter the samples follow the direct transfer method unless in other case follow membrane filtration method.

Sample preparation:

Excessive care must be exercised when opening an article so that the sample to be tested for sterility is not contaminated by Microorganisms present on the exterior part of the container. The exterior surfaces of ampoules and closures of vials must be cleansed with 70% IPA or Hydrogen peroxide. Allow for 10/15 minutes and assemble the sampling unit’s previously sterile tray at inverted position.

Transfer the samples through pass box into the sterility testing area. FTM [Fluid Thioglycollate Medium] and SCDM[Soybean-Casein Digest Medium] or TSB[Tryptone Soya Broth] is used for the sterility test. Prepare these dehydrated mediums.

Before use, each batch of medium should justify for sterility by incubating portions of the medium for not less than 7 days. Growth promotion test [Nutritive properties] should be justified.

Test for Sterility of the product/material [Membrane filtration method]:

Prepare required amount of FTM, TSB, and USP Diluting Fluid–A and sterilized it. After completion of sterilization transfer all testing materials and accessories into sterility testing area by opening sterile side door of the autoclave.

Enter into the sterility testing area through change room. Clean & sanitize the working place. Accumulate the Sterilized filtration unit cautiously, using not more than 0.45µm cellulose nitrate filters (47mm dia.). Convey samples and other equipment into testing area from pass box after cleaning the surface    with 70% IPA.

For Raw Materials transfer aseptically 5 -10 gm of tested sample into 500 ml screw caped  conical flask containing 200 ml of USP diluting fluid-A and shake gently when it completely   dissolve. For Finished Product collect required amount of test sample (see step Table) & transfer aseptically 300 mg of solids into a 500 ml screw caped conical flask containing 200 ml of USP Diluting Fluid-A and mix or constitute, as directed in the labeling, the containers and transfer a quantity of liquid equivalent to about 300 mg into a 500 ml screw caped conical flask containing 200 ml of USP diluting fluid-A.

Transfer the whole content to the filter cup assembly under strict aseptic condition. Filter the whole content with aid of vacuum pump [negative pressure] from the filter cup. If the tested sample under test has inherent Bacteriostatic & Fungistatic properties or contains preservative, rinse the filter paper using USP Diluting Fluid A.

After completing the previous step, cut the filter paper into two equal sections with sterile scissor and aseptically transfer into 100 ml bottle containing TSB & FTM media separately. Mark 1×100 mL of sterile FTM and 1×100 mL of sterile TSB medium without any sample and inoculum, as negative control.

After finishing of the test transfer out all the materials through pass box, clean the working place thoroughly and sanitize with approved disinfecting solution before leaving the area.

Direct Transfer Method:

Prepare required amount of FTM, TSB, (distribute it in screw cap 100 ml bottle) and USP diluting Fluid-A and sterilized it. After completion of sterilization transfer all testing materials and accessories into sterility testing by opening sterile side door of the autoclave.

Enter into the sterility testing area through change room. Clean & sanitize the working place. Prepare required amount of test sample (as per mention Table) and aseptically transfer it into 500 ml screw   caped conical flask containing 200 ml of USP Diluting Fluid-A, and shake it gently.

Agitate the flask and aseptically withdraw 5 ml of test specimen into both of sterile TSB & FTM medium. Mix each test specimen with the appropriate medium, but do not aerate excessively. Incubate the test mixture and both negative controls as directed in the Incubation condition. Examine the media visually for growth.

Where the material being tested renders the medium turbid, so that the presence or absence of microbial growth cannot be determined by visual examination, transfer suitable portions of the medium to fresh containers of the same medium at least once during the period from the third to the seventh day after the test is started.

Continue incubation of the original and of the transfer containers for a total of not less than 14 days from the original inoculation.

Sterility Test of Syringes ( 5 mL, 10 mL & 20 mL)

Take the required quantity of the material followed by previously mentioned table. Aseptically disassemble the syringes into the components like barrel, plungers, needle and needle shield.

Transfer half of the syringe components into one media bottle having sufficient quantity of the FTM and another media bottle having TSB so that components can submerge completely within media and if require pour additional media.

Select the bottle for sterility test on the basis of the size of the components of syringes so that upon addition of media sufficient air space will be available.

Incubation Conditions:

All the test containers, incubated for not less than 14 days at 32.5 ± 2.50C for the Fluid Thioglycollate Medium and at 22.5 ± 2.50C for the Soybean-Casein Digest Medium or Tryptone Soya Broth Medium regardless of the method used for sterility testing.

Observe the media bottle on a periodic basis over Digest Medium regardless of the method used for sterility testing. Observe the tested as well as negative control incubated media bottles on each working day for any kind of macroscopic evidence of microbial growth and record the results in the report sheet with sign and date of the observer.

Interpretations of the Results:

At intervals during the incubation period and the completion of the prescribed incubation time,   examine the media for any visible growth (Turbidity). If confusion arises, make subculture on TSA medium and/or justify evidence of growth.

If no evidence of growth is found, the preparation being examined, pass the sterility test and issue report form (Annexure I). If evidence of growth is found, isolate and identify the organism and make a full case investigation.

If the cause of microbial growth failed to reveal, perform repeat test with same number of test sample. Take double number the sample in case of high risk product.

Download : Appendix-I-Sterility Test Report

Download : Appendix-II-Sterility Test observation Register

Sterility Test, how to perform Sterility Test in the best way? Read More »

Validation Master Plan, How to write for a GMP compliance firm

Validation Master Plan[VMP] encompass all type of validation activates of a site especially for the new firm, the firm must be validated before run any routine commercial production. The validation activities which consider the major area as Facility, Utility, Machine, Process etc.. Facility, utility, and machine must be validated before run the production operation.

Validation procedure and Validation Master plan is not the same and doesn’t implies the same thing. Validation protocol describe the specific procedure to perform the specific activities where as Validation Master Plan is the series of plan/schedule which describe the plan with a tentative define timeline. Any plan/schedule may be change which to be cover by raising deviation management with proper justification and action to be triggered followed by CAPA.

Validation Master Plan is beneficial for planning purpose and subsequently identifying the related resources to complete the assigned activates on due time. It covers the all type of major documentation like procedures, processes, product, facilities, utilities and equipment.

How a Validation Master Plan works?

Validation master plan is the core guidance of the firm which implies that how the validation activates of the firm will perform within a time frame. It details the activities of the all functional department like production, quality control, Engineering will operate their activities regarding validation events.

The plan demonstrate by the Validation master plan is set upon the agreement of the all functional department and any type of failure is properly justified which satisfy the regulatory body. The proper implementation of the VMP of the respective firm denote that they have the proper control over their quality system.

Functions of the Validation Master Plan

Management learning

Top management of the company is not concern about the requirement of the qualification and validation activities of the respective firm. Here VMP plays the major role and provide the essential information to the company top management. The content of the VMP describe the total quality requirement events of the validation process. It also denote that only the properly validated facility can provide the repeated/continuous quality product through daily activities.

Project nursing and management

By preparing the Gantt chart from the content of the VMP, the management can track the activities of the new facility and set a tentative deadline for the competition of the defined activities. Everyone will be proactive when set a tentative deadline with proper justification through a site quality review meeting. Assigned personnel must be monitored for the progression of the events by daily /weekly /fortnightly/ monthly then VMP will be fully effective and action will cover on due date.

Conducting the validation program

Validation master plan describe the all events in the validation process and the qualification of the processing equipment’s and utilities. As the VMP provide the timeline for the completion of the defined activates base on the criticality. All related resource must be on site to conduct the validation activities and recheck/double/ triple check may be conduct before starting validation activities, for any shortcoming notify the same and after solving the events proceed to validation activities.

Planning purposes

As the VMP detect the list of resources which is required to perform the validation activities in a time line then the list of document may affect by this activity-

  • Equipment
  • Facilities
  • Product
  • Processes
  • Procedures
  • Utilities
Criteria of a Validation Master Plan

VMP require specific preparedness and vigorous planning of different steps in the particular process. All type of activates need to perform in due time as per approved working plan avoiding any type of major/critical deviations. Beside this a VMP is generally written off as-

Multidisciplinary methodology:

This is not the one man job, its require multidepartment involvement, various type of SME [Subject Matter Expert] from various department are involve to perform the specific job. Expert such as chemical analysts, pharmacists, microbiologists, technologists, engineers, metrologists, and SME from QA departments must involve to this activities.

Time bound:
Any type of validation

Generally validation work is submitted to rigorous time schedules. These studies are always the last stage prior to taking new processes, facilities into routine operation.

Costing matters:

To run a successful validation activities to the site, huge resources and expert personnel are involve so that no deviation occur on the site. Lot of financial involvement require to perform the designated activities. A new machine/equipment may be involve to solve the emergency issue.

List of critical point of Standard VMP

All VMPs must include the following:

Title page with Authorization where appropriate signing with date will be present. Title page must be include title of the document, document number and version no. and Signature from the appropriate body including Head of site quality. List content to be present on a VMP-

  • Table of contents
  • Abbreviations and glossary
  • Validation plan
  • Purpose and approach to validation
  • Scope of validation
  • Roles and responsibilities
  • Outsourced services
  • Deviation management in validation
  • Change control in validation
  • Risk management principles in validation
  • Training
  • Validation matrix
  • References
Table of contents

The table content is the brief of the major substance/content present in the VMP. It contains all of the critical area of VMP. Page no. to be mentioned on the table of the content page along with the major content. It will denote where will find the major content of the VMP.

Abbreviations and glossary

Abbreviations and glossary provides necessary information’s to the reader regarding the various term or short/abbreviate form use in the VPM which may not familiar to the respective reader.

Validation plan

A VMP implies that what should be validated and when, where, how and why it should be executed. Critical process mention on the VMP must breakdown into several parts and criticality must identified to perform require validation.

Purpose and approach to validation

Purpose provides an overview of the every process also describe validation approach with supporting data. It must be sum up clearly so that the respective user can understand the actual process/procedure by tracking the document. Validation approach states the persistence of the VMP denoting critical process, equipment and system as described.

This methodology confirm that all validation events to be conducted in prospective manner following approved protocols. VMP speaks about the change control and qualification of equipment and systems and confirm the stipulated events has been done based on existing policies and procedures.

Scope of validation

Scope of the VMP describe all evets relating to the processes, systems, equipment, utilities, and procedures which may affect the quality of the product at the manufacturing site.

Specific equipment, utilities, systems, and procedure be mentioned properly and validation execution to be done based on the documented risk assessment. Define clearly which area will be under validation and where not under the scope. Procedure to be describe in such a way so that anyone possess the same understanding to coverage VMP.

Roles and responsibilities

This area specially denote the dedicated responsibility for the designated department. Generally validation department/team is responsible for preparing all type of validation protocols, validation reports, List of SOP’s deviation reporting, and change control procedure and achieving, storage of validation related all documents.

Generally, Engineering, Production, QC, Microbiology and QA personnel prepare the validation documents as when required based on define timeframe subsequently. Quality Assurance department is responsible to review the all protocol, reports, SOP’s etc. then approve the same.

Outsourced services

Any type of out sources activities regarding qualification and validation must be mention the validation master plan and record/supporting documents/agreements must be keep the same. Certified vendor to be involve to the validation activities, before engage the validation/qualification activities vendor competency certificate to be check.

Deviation management in validation

Any deviation regarding validation to be address and record must be keep for further clarification, if machine involve then call the supplier to resolve the problem. All of critical deviation must be investigate and corrective action to be taken. All validation report to be approve before starting the operation.

Change control in validation

VMP must implies all change management which have the potential impact on the validated process/system must be notify and it should be handle with the existing change management procedure.

Risk management principles in validation

Quality Risk Management Procedure to be define on the Validation Master Plan as to perform the validation activities, quality risk may be the major to be notify same and record must be done and impact to be analyze properly through FMEA[Failure mode and effects analysis] method.

Training

The defined personnel who will perform the validation activates must be trained properly and to be ensure that they have the proper knowledge and skill to perform the right job at the right time.

All validations

This include the following area-

  • Analytical method
  • Cleaning
  • Computer validation
  • Equipment
  • Premises
  • Processes
  • Qualification
  • Revalidation
  • Utilities

The description of the major area must be include VMP such as Manufacturing, Material Management, Facilities, and Central Plant. Attachment with VMP must define the GMP compliance area and non-GMP compliance areas. Describe the cleaning validation strategy and manufacturing process steps, use process flow diagram to describe the specific product manufacturing activities with major equipment involvement on the diagram. Performance qualification of the major equipment to be done showing that it repeats its intended use subsequently.

Validation matrix

Performing an effective validation matrix by prioritizing the critical validation at first then the next one. In this way the VMP activities may be more fruitful. List the all critical validation then perform the task as per justified time frame.

References

List of references to be add at the end of the VMP documentation. Proper guideline reference is mandatory to prove your documented evidence.

Writing the VMP

To write the effective VMP, a team may be form due to a single/individual/specific person didn’t contain the all idea/knowledge regarding different activates. A QA person may not be expert about Engineering activates and a QC person may not be expert about production activities, so a team from different functional department may be effective way to gather comprehensive knowledge from different perspectives then write down the right VMP.

 Involving the multidepartment people from different parts confirm that all equipment, utilities, processes, and systems has been properly addressed on the VMP. T write an effective VMP, every team member must be proactive to address the every point of view seems critical to his side.

What “WHO” says about Preparation of VMP?

“A manufacturer should have a validation master plan that reflects the key elements of validation. It should be concise and clear and at least contain reference to/have a short description”.

validation master plan, validation WHO

List of Major content of VMP as per WHO GMP guideline-

  • Analytical method validation
  • Change control
  • Cleaning validation
  • Computerized system validation
  • Deviation management
  • Equipment & instrument qualification
  • Outsourced services
  • Personnel qualification
  • Premises qualification
  • Process validation
  • Validation matrix
  • Validation policy
  • References
  • Risk management principles
  • Roles and responsibilities
  • Scope of qualification & validation
  • Training
Conclusion

A well described VMP is the true asset of the firm as well as the critical document to avoid the regulatory noncompliance. An incomplete VMP always brought more 483 with subsequent warning letters from FDA. A standard VMP must be more precise, to the point and actual to the system, process, and procedure.

Every sentence of the VMP must be “may”, “may be”, “should be” etc. free, sentence must be in active form in present tense. A well decorated VMP implies the organization positive image as well as quality products avoiding non-compliance, deviation etc.

Validation Master Plan, How to write for a GMP compliance firm Read More »

HEPA filter and its multipurpose use in different area

HEPA filter, High-Efficiency Particulate Air/ High-Efficiency Particulate Arrestance Filter / High-Efficiency Particulate Absorbing Filter is known as HEPA filter denote higher degree of efficiency. The efficiency level denote the grade of the HEPA filters. There are several grades of HEPA filters available as per their area of application.

HEPA filter, different  particle size

A standard HEPA filter must remove the particles from the air at least 99.5%[EU standard] or 99.97%[ASME,US.DOE] having particle diameter equal to 0.3 μm and subsequently increase efficiency with particle diameter greater than or equal to0.3 μm.  

All type of standards HEPA filter generally retain particle and microorganism like dust, pollen, dirt, moisture, virus (0.02-0.3 μm), bacteria (0.2-2.0 μm), Bacillus subtilis, submicron liquid aerosol (0.02-0.5 μm), Penicillium citrinum, Aspergillus niger, Clostridia, Staphylococcus epidermidis, Bacilli, Bacteroidia, photocatalytic oxidation (PCO) etc.

HEPA filters use in wide area since its commercialization at 1950 where need to control contamination-

  • Aerospace industry
  • Cosmetic industry
  • Materials dispensing area
  • Electronics
  • Food Industry
  • Hard disk drives mfg. industry
  • Hospitals
  • Medical devices
  • Microbiological Lab
  • Nuclear Plant
  • Pharmaceuticals
  • Sterile products mfg. facility
  • Semiconductor industry
  • Vaccine and blood products mfg. area
  • Vehicle industry

Type of HEPA filters

Generally HEPA filters can be classified as [A], [B], [C], [D], [E] and [F]. Types testes are demonstrates on the following table.

HEPA filter, classification of HEPA filter,

How it works?

All type of HEPA filters are generally composed of mat where fibers are randomly arrange, these fibers are actually set of poly propylene or fiberglass varies diameter between 0.5 and 2.0 micrometers. Frequently use tangled bundles of fine fibers to prepare these filters. Air passes through the convoluted pathway crated by the tangled bundles of fine fibers.

Actually this fibers act like sieve which retain the big particles which subject to try pass through it. Most time the smaller particles can’t hold its motion when they are passed with air, in result the small particle crush with the fibers. As per Brownian motion, the small particle possess the little materiality to move randomly with air as these particles are suffered to bombard action.  

As the small particles crush with the fibers, here the key factors are mainly filter thickness, fiber diameter and velocity of the air. The air space between the HEPA filter subject to greater than or equal to 0.3 μm provide high level of efficiency. In sieves or membrane filters, particles which are less than the pore or openings can pass through but in HEPA filters the particles are attached to the fibers. There are several mechanisms has been identified which play the major role trap the particle to the pore.

HEPA filter, Filtration mechanism,

Diffusion

All the particles under 0.3 μm retained by the HEPA filter in diffusion method. This the main theme of the Brownian motion where smaller particle below or equal to 0.1 μm in diameter are hindered and trapped in the filter. This mechanism is not prominent is low velocity of air.

Interception

Particles which are subject to flow in a line come with same radius/diameter of a fiber and adhere to it, this is very prominent to mid-size particle and which are retain by this process.

Impaction

Particles with higher diameter subject to unable to pass the fibers and directly retain on them, the effect increase subsequently with the air velocity.

Particle having size at or below 0.1 μm diameter, diffusion method is predominant and particle above0.4 μm predominant to impaction and interception. The MPPS [Most Penetrating Particle Size] is 0.21 μm, here the impaction and interception are remarkably inadequate. And this this point consider the weakest point of HEPA filter. The classification of the HEPA filters remarkably depend on the particle retention capacity at or below or equal to 0.3 μm particle size.

What is Gas filtration?

All types of HEPA filters are designed to retain particles but HEPA filters are unable to retain odor and gases molecules. HEPA filters can’t filter the odor or gases molecules. Alternative have been developed by British Armed Forces[BAF]. To filter the chemical vapors, organic compounds, volatile compounds, pet, cigarette, or flatulence odors, activated carbon filter or other filters are used.

HEGA [High Efficiency Gas Adsorption] filters plays the major role here, composed of Carbon cloth filters which is more efficient than granular activated carbon form. This filters [HEGA] designed by BAF to face chemical warfare.

Effective Usage of HEPA filter with Pre-filter

In a common air handing unit, a pre-filter[Carbon activated] use with the HEPA bag filter to extend the usage life/shelf life of more expensive HEPA filter. At the first stage of the filtering the pre-filter, removes the almost all type of dust, hair, particle from the air. Particles which can’t remove by pre-filters or escape from it then the fine particles remove by the HEPA filters in AHUs[air handling units].

Specifications of HEPA Filter

HEPA filters are defined by the US, DOE[United States Department of Energy] in almost all American industry which removes at least 99.97% of particulate at 0.3 μm in diameter. At the standard volumetric air flow, the minimal resistance of the air flow or pressure drop is around 0.044 psi[300 pascals].

In EU, filters are classified based on MPPS [Most Penetrating Particle Size] as HEPA, EPA, and ULPA where the average efficiency defined as “Overall” and the specific point efficiency defined as “Local”.

Marketing View Regarding HEPA Filter

Now a days some of the company highlighted the term “True HEPA” supposed to give assurance to the end user/customer to confirm that their filter is the original HEPA filter. This term “True HEPA” has no significant scientific value or no legal meaning. Some of the company marketed as designed as”99% HEPA”,”HEPA-style””HEPA-like,” “HEPA-type,” etc. which didn’t comply the HEPA standard[99.97% efficiency] and this type of material may not have the original test certificate of may not undergo any type test like filter integrity test.

Safety consideration of HEPA Filter

Mid-size particles ranges between 0.15 µm and 0.2 µm is considered hardest to filter through HEPA. The mechanism of working of HEPA filter is totally different from Ionic filters and Ozone filters which work through negative ions and ozone gas respectively. So HEPA plays a great role in pulmonary side-effects like asthma and allergies which are much lower with HEPA filters.

Where the HEPA filters subject to use in commercial grade, it is better practice to change the HEPA filter in every six month to hold its efficiency at desired level of work but if it use in residential purpose then it may be change in every two to three years. In the period of time, the efficiency of HEPA filters decrease day by day and failing to change the same in due to create hazard to the machine or system and particulate contamination spread day by day.

Applications of HEPA filters

Biomedical

HEPA filters generally remove the air borne particle, bacteria, virus and various type of organism resulting infections. High energy ultraviolet light units or panels with anti-microbial coating integrated HEPA filters are specially use to serve medical purpose to kill the live bacteria and virus which trapped by the filter media. Airborne disease transmission successfully protect by the special design HEPA filter which efficiency declared as 99.995%.

Heating, ventilation, and air conditioning[HVAC]

HVAC [Heating, ventilation, and air] technology uses HEPA filters to remove airborne particulate, dust, microorganism etc. in indoors and vehicle, greatly use in sensitive pharmaceutical product manufacturing where subject to clean room class. To ensure better environment and better health, HVAC play a major role various organization who are concern this activities.

COVID-19

HEPA filters plays a great role to get entrapped SARS‑CoV‑2 Airborne droplets which size approximately 0.125 µm even if they are present on the floor. Various type of HEPA incorporated mask are available at the current market which is the best solution to prevent the pandemic situation for personal use.

Motor vehicles

HEPA filters is using in the latest car, “Tesla Mode X” using HEPA filters since 2016 and now their update “Model S” also using the additional HEPA filter.

Vacuum cleaners

HEPA filters are also use in many well designed vacuum cleaners as a part of their filtration systems. This option of the vacuum cleaners plays beneficial role for the patients having asthma and allergy problem due to HEPA filters traps fine particles reduce to size 0.1 µm which is mainly responsible to induce asthma and allergy. Before using the Vacuum cleaner integrated with HEPA filters, check the filter efficiency [at least 99.97%] unless authorized. HEPA like, True HEPA, HEPA are not the actual term to declared standard HEPA efficiency.

A powerful motor is essential to provide adequate cleaning power due to the high density of the HEPA filters. A vacuum cleaners containing washable HEPA filters subject to more expensive. A standard high quality HEPA filter generally trapped the particles having 0.3 µm in diameter where a natural human hair is 50 to 150 microns in diameter. So a HEPA filter traps the particle which are reduce to several hundred times smaller than the standard width of Human hair.

Sometimes, is remarkably noticeable that some of the manufactured declared HEPA 4/HEPA 3/HEPA 2 etc. without proper explanation behind them.   This is actually declares their MERV [Minimum Efficiency Reporting Value] rating. This the ability of the air cleaner filter to remove the particle, dust, and microorganism etc. which passes with air through the filter. The MERV scale distributed between 1 and 16 which declare the efficiency of the filters remove particle between 10 to 0.3 µm in size.

Vehicles

Airlines

All types of modern airlines uses HEPA filters to reduce contamination in the air. As most of the air in air plane cabin is recirculated, so this is crucial to filter the air using high grade of HEPA filters to avoid cross contamination.

Maximum quantities of standard pressurized aircraft brought air from the outside and circulate it the cabin exhausted it through the outflow valves in the rear side of the respective aircraft. Almost 60% of air comes from outside of the plane and 40% cabin air passes through the HEPA filters in well-designed aircraft.

What are drawback of HEPA filters?

Every filtration technology has the shortcomings that no filter can pass the 100% contamination free air. The efficiency is almost 99.9997% not 100% same for HEPA filters. Besides this the HEPA filter has the following two types of drawback which can dissatisfy to you to buy a HEPA filter/HEPA filter integrated equipment’s-

Insignificant Pollutants Can Escape Filter:

HEPA filters are effectively act on the particle size at equal to or above 0.3 µm, there various type of microorganism which particles are reduce <0.1µm can easily pass the HEPA filters. So using HEPA filters you can trap/remove all type of organism, this myth is actually invalid. The smaller particulate cause the serious health hazard for the patient/personnel who are previously suffering from asthma or allergic problem. Alternative technology should be used to face this tiny size particles.

Various type of Mold & Bacteria Growth on Filter:

When bacteria and mold gather on the air system on the HEPA filter, this accumulate organism have the potential chance to grow in geometric order. As the number of the microorganism tend to grow outside the filter then the health hazard outside the controlled environment growth day by day. To solve this issue, a UV light integrated HEPA filter to be use to kill the mold and bacteria at your indoor environment.

HEPA filter, health hazard,

So what is the best alternative of HEPA filters?

The best alternative of HEPA filters are ULPA [Ultra-low Penetration Air] filters. HEPA filters remove particles size equal to or above 0.3 µm having efficiency of 99.97% where ULPA filters remove particles size equal to or above 0.12 µm having efficiency of 99.999%.

Can HEPA filters be Wash or Reuse?

All type of HEPA filters can’t wash. Some of the HEPA filter can be wash and some are not. If your HEPA filter labelled with “Washable” then you can wash the HEPA filter but a non-washable HEPA filter may be wash by appropriate way.

To rinse a HEPA filter decrease its efficiency and proper study didn’t found that how much efficiency loss upon rinsing the HEPA filters. Moreover, this has been proved that upon rinsing the HEPA filter, its efficiency loss due to losing/damaging of fiber occur in this time.

During cleaning of HEPA filter, if individual face lack of awareness, fall in serious health hazard upon accidentally taking some of pollutants from HEPA filter. After cleaning, drying activity must complete for a long time. Check the same before use as the wet filter is the great source of mold.

HEPA filters can be reuse if you can clean it properly. Use a vacuum cleaner to clean the filter rather than rinse it. Even non washable filter can be clean this way, proper measures to be taken before cleaning the HEPA filter. Avoid direct touching it. If you rinse your filter, the dry the filter properly by placing it outdoor. Before placing, shake the it to remove the water properly. Set it at outdoor in such way that it get air from all direction and faster the drying process.

After washing the filter may withheld its efficiency maximum 99.7% and you can was your filter every six months or once in a year but it is the best practice to replace the same. Some of the filter labelled with “Permanent” then you can’t wash it, just replace it.

Also Read

Poly Alpha Olefin(PAO) in HEPA filter Integrity Test at HVAC Qualification

HEPA filter and its multipurpose use in different area Read More »

Poly Alpha Olefin (PAO) in HEPA filter integrity test at HVAC qualification

Poly Alpha Olefin (PAO) is used in in HEPA filter integrity during validation of HVAC system in different pharmaceuticals. This is the best alternative of DOP which was previously used for the same purpose as PAO is subject to use. DOP was using long time for HEPA filter integrity test during HVAC qualification.

Poly Alpha Olefin (PAO),

International Agency for Research on Cancer (IARC) has classified DEHP/DOP as carcinogenic 2B substance According to evidence from rodent studies which has also been identified carcinogen (cause cancer) for the human. For this reason scientist was trying to replace DOP for similar materials for a long time.

In 2021, JICA[Japan Air Cleaning Association] introduce a guideline to substitute the DOP[Dioctyl phthalate] with PAO[Poly Alpha Olefin]. PAO provides the same performance as provided by DOP additionally doesn’t provide any harmful/carcinogenic effect to human.

Food and Drug Administration[FDA] stated that the alternative aerosols are also suitable but it shouldn’t promote the microbial growth in the respective area. Generated aerosol ranges from PAO[Poly Alpha Olefin] is 0.1 to 1.0μm.

The aerosol generator, generate the PAO aerosol and subsequently passed through the HEPA[High-Efficiency Particulate Absorbing/High-Efficiency Particulate Arrestance/ High Efficiency Particulate Air having six types A, B, C, D, E & F] filter and then with the help of a Photometer the integrity is checked as 99.97% particle contains size 0.3 μm shouldn’t pass to the HEPA filter.

Chemically, PAO is the polymer of alpha-olefin which is the class of Olefins those contains double bond between first and second carbon of the polymer chains.  Poly Alpha Olefin is the mixture of dimers, trimers and tetramers of 1-octane, 1-decane and 1-dodecane in chemically.

 DOP[Dioctyl phthalate]

Poly alpha olefin is a polymer of alpha-olefin. Alpha-olefin is a class of olefins those have a double bond between first and second carbons of the polymer chains. PAO contains better lubrication properties and having greater viscosity compare to mineral oils. Poly-alpha-olefins have good lubrication properties and greater viscosity than mineral oils.

Poly alpha olefins are also used as a coolant in radiators and synthetic lubricants. Generally, the declared shelf life of PAO is 10 Years but when subject to open the container, the shelf life down to only one year. This is the best practice to protect PAO from direct exposure of sunlight and protect from UV light.

Why DOP[Dioctyl phthalate] banned?

Due to carcinogenic effect for human using of DOP [Dioctyl phthalate] was banned in pharmaceutical company, additionally DOP has the following significant effect which is also the major cause to ban the DOP.

Endocrine disruption

Causes endocrine disruption in male, act as androgen antagonist subsequently effect on reproductive system. Exhibits insignificant levels of reproductive function in adolescent males in Prenatal phthalate exposure. Chromatin DNA integrity and Sperm motility expressively reduce in PVC pellet plant where presence of higher airborne concentrations of DOP. Subsequent study has been proved that the significant exposure of DOP reduce the Chromatin DNA integrity and Sperm motility in men.

Development

Several studies have been shown that significant exposure of DOP has been change the sexual function and development in rats and mice. During pregnancy, excessive exposure of DOP disrupt development and placental growth in mice which cause premature birth, low birthweight, and fetal loss. Advanced levels of anxiety during puberty and hypertrophy of the adrenal glands may arise if excessive DOP exposure occur in neonatal mice through lactation.

Obesity

Intestinal lipases convert DOP to MEHP upon DOP ingestion then MEHP absorbed. MEHP is considered for the obesogenic effect. DOP is the possible disruptor for the thyroid function which have already verified by human studies and rodent studies. Subsequent exposure of DOP is significantly relevant with plasma thyroxine levels and patient with hypothyroidism inclined to to weight gain.

Cardiotoxicity

A minor dose of DOP predominately effect the activity of mice. The duration of the exposure of and clinical dose of DOP has the significant effect of the behavior of cardiac cell at culture. Cell face the slow propagation speeds with fractured wave fronts.

Also Read

HEPA Filter and its multipurpose use in different area

Poly Alpha Olefin (PAO) in HEPA filter integrity test at HVAC qualification Read More »

Mix Up, Contamination and Cross Contamination in Pharma industry

Mix up

Mix up can be defined as taking something which is not subject to take; taking one thing to another. Taking wrong item unintentionally which can be easily identified such as taking Aceclofenac tablet in place of Metronidazole tablet having different size and shape. Mix up is a mix of diverse item but essentially contaminated. For example one blister strip of batch [A] tablet found with another batch [B] tablet.

Mix up is

  • Assume wrong item to right thing
  • Failure to take right action on due time
  • Mixture of various item/elements
  • Selection of wrong item
  • Selection similar product/material/item
  • Unintentionally taking one thing to another
  • Wrong selection of desired material
  • Wrong action taken due to lack of attention

Probable cause of Mix up

  • Breakdown of processing equipment.
  • Collation/procure similar packaging/printed material from same vendor.
  • Conducting packaging operation in other than main packaging belt.
  • Discontinuous packaging/partial packaging of single batch.
  • Engaging untrained/partial trained personnel.
  • Engaging single operator to multiple packaging line.
  • Failure to follow written procedure for line clearance.
  • Inappropriate labelling.
  • Improper segregation of products/item during manufacturing operation.
  • Improper labelling during dispensing.
  • Inadequate controls.
  • Manual operation other than automated system
  • Multiple product packaging operation in insufficient packaging area.
  • No barcode/QR code/Identification code
  • Process validation not properly conducted
  • Previous batch item such as label, carton, accessories etc. not removed properly
  • Rejection material handling
  • Reprocess
  • Rework
  • Return of IPC checks item to the wrong/ similar packaging belt.
  • Repackaging and packaging of similar product/item.
  • Similar Size, shape, color of multiple products.
  • Similar design of primary packaging/secondary material.
  • Similar product line clearance in same time.
  • Same instruments/apparatus use for multiple item/products/material.
  • System failure
  • Wrong labelling

Contamination

Contamination can be defined as the presence of undesirable element, impurity or constituent which infects, corrupts, spoils, makes substandard or makes unhealthy a factory, normal environment, physical body, material, process steps, bulk, liquid, granules, solid etc.

As per US FDA, contamination can be defined as-

cross-contamination, contamination

Type of Contamination

Non-Viable

Liquid or solid particulate contamination range from 001 and 1000 microns such as smoke, dust, fogs, fumes, and mists.

Viable

Particulate contamination that supports, or consists of one or more live microorganisms such as Viruses, Bacteria, and spores.

Sources of Contamination

  • Atmosphere
  • Clothing
  • Equipment
  • Fluid
  • HVAC System
  • Manufacturing Debris
  • Premises
  • People
  • Processing Operations
  • Surface
  • Utilities and Services

Various source of contamination has been illustrated on the respective table-

Contamination of products can be caused by:

  • Contaminated dress/attire
  • Contaminated equipment/apparatus/instruments
  • Contaminated or damaged HVAC system
  • Contaminated Premises/sites/areas
  • Individuals, e.g., carrying harmful bacteria
  • Processing Operations negligibly
  • Utilities/Services/facilities

Cross Contamination

Cross Contamination can be defined as unintentional transfer of chemical contaminants, microorganism from one person, food, and object to another person, food.

Risk of cross contamination

The involving risk of cross contamination depends on the type/class of contaminant and which product or item will be affected.

The most hazardous contaminant are;

  • Allergens
  • Biological item/product/living organisms
  • Hormones
  • Sensitizing materials
  • Toxic materials/Item

Sensitive product for contamination

  • Administer booster doses
  • Injections
  • Prolong period of time
  • Product Applied to open wounds
  • Cytotoxic agents

Consequences to Company

  • Company image crisis
  • Financial losses
  • Loss of Company reputation / Adverse Publicity
  • License cancellation
  • Market share down
  • Product Recall
  • Show cause notice
  • Shutdown of premises
  • Vigorous audit by regulatory authorities
  • Withdrawal of product
  • Warning letter

Employee Consequences

  • Financial losses
  • Jail / Penalty
  • Reputation loss
  • Personal Image crisis
  • Suspension order
  • Show cause notice
  • Termination of services

Minimizing the risk of cross contamination

Minimizing the risk of cross contamination from mix up

  • Allocation and utility connect expertise that are exclusive to the process
  • Bar coding, QR coding, and RFID of materials and equipment’s
  • Distinct dispensing areas
  • Enormous Electronic confirmation of material
  • Enormous manual check
  • Isolated raw material staging area with proper labelling
  • Using of Color coding
  • Using of Locked and key Stainless steel cages to store APIs with chain of safekeeping
  • Using of PAT [Process analytical technology, i.e. NIR]

Minimizing the risk of cross contamination from residue carryover

  • Cleaning validation
  • Distinct product contact parts
  • Equipment design for CIP and SIP
  • Single use product contact parts
  • Process Analytical Technology [PAT]/online monitoring
  • Setting of cleaning limit
  • Set base limits on statistical analysis, science, and risk assessment

Minimizing the risk of cross contamination from Mechanical Transfer

  • Airlocks system
  • Cleaning mobile equipment’s/machine in processing room/area
  • Encompass at the source
  • Gowning procedures
  • HSG [High Shear Granulator], Milling and Drying in same suite
  • Limiting the transfer of compounds between same suits
  • Room Airflow
  • Separate work areas to a single product
  • Sprinkling showers
  • Wipe down protocols for mobile equipment’s

Minimizing the risk of cross contamination from Air borne transfer

  • Airlock separation to corridor
  • Appropriate Room air changes rate
  • Comprehend the source
  • Close process systems
  • Gowning procedures
  • Room differential pressure
  • Sufficient Room airflow
  • Sparking showers

Also read

Cross-contamination prevention during processing in pharma industry

Mix Up, Contamination and Cross Contamination in Pharma industry Read More »

Cross-Contamination prevention during processing in pharma industry

Cross-contamination, Before taking steps regarding Prevention of Cross-Contamination during processing, this is very important to know basic about contamination and Cross-Contamination and what is the basic difference between contamination and Cross-Contamination.

Also Read

Mix Up, Contamination and Cross Contamination in Pharma industry

Cross-contamination

Cross-contamination can be defined as unintentional transfer of chemical contaminants (including allergens), microorganisms, or any other foreign substances from person, food, or object to another person, object or food product.

This problem is generally occurs  at raw food to RTE[ready-to-eat] products, also occurs between allergen free and allegen products.

Cross-contamination products can cause severe food poisoning as harmful bacteria transfer from RTE products which doesn’t subject to any type processing or treatment on not taken any steps to eliminate harmful bacteria from those foods[RTE]. The best example of cross contamination is transfer of bacteria from raw food to cooked food.

Pharmaceutical products are the highest risk of Cross Contamination. Presence of small amount of antibiotics or trace amount of potent drugs cause severe damage to the patients. Carryover of one products residue to another products is consider the highest risk to the patient.

In the recent year, as per UK MHRA[United Kingdom Medicines & Healthcare Products Regulatory Agency], product contamination is the second to third cause to recall products from the market.

Understanding Cross-Contamination

There are several ways to where cross-contamination can occur:

  • Equipment to food
  • Food to food
  • People to food

Equipment to Food

Contamination can be transfer from pantry equipment & utensils to food staff. This type of contamination can be transfer from improper cleaned equipment or utensils to food items and which is not properly sanitized before each use. Here is some example-

  • Using of improper cleaned items such as utensils, slicers, knives, grinder, and juicer to prepare food.
  • Using of cutting and chopping board and use the same knives to cut different food items, such as cutting raw beef and then prepare vegetable salad or RTE food items.
  • Storing RTE [ready-to-eat] food items in an improperly sanitized container, which was previously used for raw food item such as raw beef.

Food to Food

Food can contaminate by bacteria from comes from other foods. This type of cross-contamination seriously dangerous when raw type foods contact with cooked/finished food/RTE Food. Here is some example for of food-to-food cross-contamination-

  • Storing raw chicken in the upper shelf of the refrigerator but cooked chicken store lower shelf of the refrigerator where cooked chicken dripping from raw chicken.
  • Raw meat placed on a on a grill touching another meat that is being cooked.

People to Food

Personnel can be great source of cross-contamination to food items for their inappropriate behavior or lack of training to do the task properly. Here is some points to notify the situation-

  • Handling of food items just using after the toilet without properly personal clean up.
  • Touching Raw Chicken and prepare vegetable salad without properly clean up between the tasks.
  • Handling of apron with wipe hand and subsequently serve foods to individual.
  • Using of towel to clean the kitchen and further use the towel after dry hand.

How to prevent cross-contamination

Production & Related Area

  • All type of line clearance should be perform as per approved SOP and related checklist mentioned on BMR/BPR
  • Avoid similar type of product clearance in same time in side-by-side line.
  • All the system must be properly validated [Equipment/Machine/Facility/System/Process etc.]
  • Before starting of any type of product processing, processing product, list of materials, printing materials, primary packaging materials must be contamination free.
  • Check any type or related starting materials, product residues, products, documents, records, process flow and related documents of the previous products during starting of the new line.
  • Closed system to be introduce for critical products, if possible close system to be introduce for all type of products handling.
  • Campaign production may be the best procedure to achieve satisfactory contamination/cross-contamination free products by following appropriate validated cleaning procedure.
  • During processing, products and direct products contacts part should not be handled with bare hand, use latex free gloves to handle the same with properly spray cleaned with IPA [70% IPA]
  • During production/processing all type of maintenance work must be prohibited and production/processing to be stop during maintenance activities.
  • If any area subject to maintenance activities, to restart of the operation, the area must be properly cleaned and maintenance clearance to be ensure from respective department.
  • Packaging must be properly segregate from processing/filling area, a physical barrier must be introduce to prevent contamination and related operation must be controlled.
  • Product subject to in process control in production area to be confirm that it should not provide the risk for the product and remaining IPC products must be discard and not to add the processed products.
  • Production accessories/stationary/liquid item/ink of image printer/other solvent etc. must be kept in labelled container as per their content present in the defined container.
  • Single line processing to be introduce, never start multiple line/product in the same line
  • Solution container subject to filling should be properly cleaned before using for filling operation especially for aseptic products such as eye drops, which cannot be terminally sterilized due to container criteria [Plastic container].
  • Try to reduce bioburden especially for injectable products and remove outer additional/unnecessary/additional wrapping during delivery at the point of use.

Clothing & Hygiene

  • Appropriate clothing and gowning system to be ensure as per classified area.
  • Clothing should be different for every shit/working hour/every time before entering the processing/filling area.
  • Cleaning agents to be use in proper quantity and agents must be contamination free
  • Clothing and its quality should be appropriate for the process and the grade of the working area.
  • Daily environment monitoring by particle counter machine, air sampling, settle plate count to be carried out as when appropriate.
  • During handling of hazardous material/container/liquid/gas, appropriate PPE[Personnel Protective Equipment] should be ensure.
  • Footwear to be clean properly and each pair of clean shoe to be confirm before entering to the processing/filling area.
  • Lint free non-shedding cloth to be ensure.
  • Minimize the exposure of body surface as less as possible.
  • Repeated wear of same gown in same days must be avoid in processing/filling area.
  • Separate/dedicate PPE to be ensure for beta-lactam and non-beta lactam, other antibiotics, hormone, generic medicine, cytotoxic etc. products.
  • Slippery sandal/shoe/loose shoe etc. to be avoid and appropriate shoe to be use such as lint free clothing shoe to be ensure especially in sterile processing/filling area.
  • Wash the cloth each time before entry of the process room.
  • Washing system to be separate as per designated area.

Utilities and Service

  • Appropriate water to be use in pharmaceutical preparations for its targeted use.
  • Any type of failure regarding water quality test must be notify and action to be taken and production must stop.
  • Chemical and microbial limits and requirements must be made.
  • Validation of the water system to be ensure before using water in pharmaceutical preparations especially First and Second phase must be validate and third phase must be ongoing and report should be made.
  • Water quality must be check before its use.

Steam Quality

  • PQ[Performance qualification] of steam to be ensure.
  • Pure steam and industrial steam to be use as when and where appropriate.
  • Steam must be additive free.
  • Steam must be contamination free and microbial quality must be passed.

Compressed air/Transportation/Cleaning and related activities

  • Air quality to be ensure by passing through appropriate filter.
  • Any sign of spillage/broken/contamination during transport, full quantity must me discard.
  • All type of processed or partially processed, in-process materials, raw materials, partially packed, finished packed should be properly labelled with Product Name, Batch no., Quantity, Packed by, Packing date, Manufacturing date, Expiry date etc.
  • Cleaning solvent/materials use for cleaning, lubrication, pest control should not direct contact to the product and suitable grade of cleaning agent to be ensure.
  • During production, high degree of cleaning and sanitation to be ensure before entering into the processing/production area.
  • Measures must be taken to prevent cross-contamination and its effectiveness to be ensure.
  • Processing/manufacturing area for hormones, penicillin, cephalosporin, generic products, vaccine, antibiotics must be dedicate/segregate to prevent cross-contamination.
  • Transport of Beta lactam and non-Beta lactam antibiotics should not be perform in disclose condition, container must be tightly bind with the appropriate material/stripe. Finished product may be transport with tight pack condition simultaneously.
  • To be clean/clean label should be properly attached on any containers subject to use or unused with product/material name/batch no.

Cross-Contamination prevention during processing in pharma industry Read More »

Granulation Process, theory of granulation in pharmaceutical company

Granulation, Generally, all of the particles are distributed in irregular manner, when particles create bond between them then granules are formed. To create bond between the particles is not automatic process, mechanical forces are applied to the particles or various types of binding agents are used to create granules. Granulation is simply a particle collecting process where particles are particles create bond between them by compression or with the help of binding agent.

List of binding agent used in pharmaceutical company in granulation process of different material-Various types of binders use in pharmaceutical industry such as-

Natural Binders

  • Alginic Acid
  • Acacia
  • Cellulose
  • Gelatin
  • Pregelatinized Starch
  • Starch Paste
  • Tragacanth

Synthetic/Semisynthetic Polymer

  • Ethyl Cellulose
  • Hydroxy Propyl Methyl Cellulose (HPMC)
  • Hydroxy Propyl Cellulose
  • Methyl Cellulose
  • Microcrystalline Cellulose
  • Polyvinyl Pyrrolidone (PVP)
  • Polyvinylcaprolactam
  • Polyethylene Glycol (PEG)
  • Polyvinyl Alcohols
  • Polymethacrylates
  • Sodium Carboxy Methyl Cellulose

Top Binder Manufacturer

  • BASF Company
  • Colorcon
  • Dow Chemicals
  • FMC Corporation
  • Natural Starch and Chemical Company
  • Penwest Pharmaceutical
  • Quest International Group
  • Wolff-Cellulosics

Most of the granules size distribute from 0.2 to 4.0mm and this size may be change based on their mode of use. Granulation process refers to the activity where particles are adhere to form larger and this repeated procedure create multiple particle entities called granules. Granules are formed from series of primary particle, after completion of the process the identity of the primary particle is no longer available.

Objective of Granulation:

1. To produce quality product is the top most priority of the granulation process.

2. To avoid segregation of the ingredients in the powder mix.

-Different size of particle presents in particle mix, segregation mainly occur for the different size of particle with irregular ratio in power mix. Normally two types of particle present in a mix. Normally smaller and coarser particle tend to settle down in the bottom of the container and comparatively large particle store on the top of the container. If granulation process conducted standard way then no particle settle down on the container.

If segregation of the powder mix occur then, tablet compression leads to irregular pattern. Physical criteria didn’t match as per set parameter then directly affect the product quality. To avoid this problem, granulation process to be conduct by using suitable binding agent from appropriate source. Correct proportion of particle mix prevent settle down of the granules.

3. To increase the flow properties of the powder mix.

-Powder contains small size particle, irregular shape or surface characteristics denote poor flow property as the cohesive forces are not dominant here. Cohesive forces to be increase to get better flow property of powder. If cohesive forces is not dominant, particles are generally settle down to the bottom of the container.

4. To produce even mixtures.

5. To control powder density.

6. To produce dust free preparation.

7. To remove poor content uniformity.

8. To increase the compaction characteristics of the Mix.

9. To seizure and fuse small quantities of active material.

Mechanism of Granulation: How granules are formed

In pharmaceutical industry, granulation is the key step to prepare any type of tablets, pellets, powder for suspension and related powder products. So this is very important to know how to develop gangues from powder. How granules quantity may be develop and how we can overcome associate problem during granulation.

This is very important to form bond between powder particles as they adhere between them form particle-particle bond. The bond formation to be adequately strong so that they can overcome the breakdown tendency during subsequent handling.

Type of bonding mechanism: Five Types

  • Solid bridges
  • Mobile liquid films
  • Immobile liquid films
  • Mechanical interlocking
  • Attractive forces between solid particles
granulation, bonding mechanisms between particles

Methods of Granulation

Wet Granulation

Dry Granulation

granulation, method of granulation

1. Adhesion and cohesion forces in immobile films

granulation, Adhesion and Cohesion

In the presence of sufficient liquid in powder mix to form thin and immobile layer then inter-particulate distance will be reparably decrease and subsequently contact area between the particles will be increase.

granulation, Adhesion and Cohesion

Due to more surface availability bond strength between the particles will be increase, as per Van Der Waals force of Attraction, the forces are proportion to the particle diameter and inversely proportional to the separation distance.

granulation, Van Der Waals Force

During Dry Granulation, the pressure will increase the contact surface between the layers and subsequently decrease inter-particulate distance in the result; this will contribute the granule strength.

In the presence of highly viscus solution of adhesive, the thin, immobile layer form which will strengthen the bond between the particles compare to mobile films.

2.Interfacial forces in mobile liquid films

In the time of wet granulation, sufficient liquid is added to the powder and this liquid distributed around and between the particles. Sufficient liquid help to exceed the immobile layer to convert into the mobile film. Several types of water distribution systems which has been demonstrate here-

granulation, water distribution in granules

Pendular Phase:

During this phase, lens shaped rings of liquid hold particles where as this phase generally occur low moisture condition in the powder mix. Surface tension forces in the liquid-air interface and the hydrostatic suction pressure in the liquid bridge cause adhesion.

Funicular Phase:

This is the intermediate stage between the pendular and capillary phase when air start to displace between the particles then the particles arrange funicular phase. After completion of the intermediate phase- Funicular Phase then capillary phase visible where air completely displace/remove between the particles.

Capillary Phase:

As all the air remove between the particles, the Capillary Phase arrive and the entire particle held by the help of capillary suction in liquid-air interface at the granule surface. Tensile strength increases almost three times in moist granule in capillary and pendular phase.

The total moisture content plays a vital role in the phase of the power bed where total moisture content is the key factor, if separation of the particle can be decrease capillary phase may be reached easily which is the most desirable phase in granulation.

Droplet Phase:

This is the most undesirable phase in granulation. This phase is important in granulation at spray drying of suspension.

Mechanism

During the wetting and mechanical handling of particulates, the Agglomeration, granulation and pelletizing processes is greatly involved. If we increase the wetting and mixing, then open and porous agglomerate structure changes into more close and grain like granule structure. The control of moisture is the main factor in particle engineering, energy input require achieving desired structure of the granules.

Generally wet bridges considered as temporary structure as the moist granule will be dried in the certain period of time. This phase is measured prerequisite for the creation of solid bridges which is created by adhesive present the liquid.

3. Formation of Solid Bridge after Evaporation:

Solid bridges:

First, solid bridges formed by the help of adhesives present in the liquid or dissolving materials present in the granulating liquid. This can be formed in several ways-

  • Partial melting
  • Hardening binders
  • Crystallization of dissolved substances
agglomeration

Partial melting

Most of the low melting substances present in granulation process melt down by applying of pressure in the dry granulating process. Particles are readily bind with one after another and crystallization develop as the applying of pressure.

Hardening binders

By the help of adhesive which add to the granulating solvent, the liquid form liquid bridges, and upon drying the adhesive harden the phase and form solid bridges and bind the particles together. Common uses binders like PVP[ Polyvinylpyrrolidone], CMC[Carboxymethylcellulose], starch etc. plays the vital role.

Crystallization of dissolved substances

The powdered ingredients use in the solvent use in wet granulation may partially dissolve the powdered ingredients. At time of drying of granules, crystallization of powder material occur and act as hardening binder.

Drying rate of the granules are greatly hampered by the size of the crystals create in the bridges, larger the particle size will require more drying time and vice-versa.

4. Attractive forces between solid particles

There are two types of attractive forced which can operate between particle in pharmaceutical system beside the liquids and solid bridges formed by binding agents, demonstrate here-

•Van der Waals forces

•Electrostatic forces

This to me mention here that the Electrostatic forces don’t contribute to the final strength of the granules moreover this is important in the powder cohesion and initial formation of agglomerates e.g. during mixing. This force may be increase during when grain sizes decrease.

Van der Waals forces having four orders of magnitude which consider the greater compare to electrostatic and add great strength to the granules. When the distance between adjacent surfaces decreases then the magnitude of these forces increase. Dry graduation process is achieved by applying the forces to the particles.

Van Der Waals Force Interaction

5. Mechanical Interlocking:

mechanical interlocking phases that the adhesion occurs when adhesive properly penetrates into the holes, crevices and pores, and other loopholes of the adhered surface of a substrate and which locks mechanically of the substrate and must have the right rheological properties which will help to penetrate pores and other opening in due time.

Adhesion

Besides adsorption, there are Four other mechanisms of adhesion has been projected.  The first mechanism is mechanical interlocking, which occur when adhesive drifts into the pores in the adhered surface. The second mechanism is interdiffusion, result when liquid adhesives are subject to dissolve and diffuse in the adhered materials. Adsorption and surface reaction projected to third reaction.

Mechanisms of Granule Formation:

a)Nucleation

Particle with particle[Particle-particle] contact and adhesion for liquid bridges is the key factor in the Granulation process. Particles are joined together to form pendular phase. Application of agitation, desifies the pendular forms and form the capillary phase and this form act as nuclei for granule growth and the next phase.

b) Transition

Nuclei can grow in two ways e.g. Single particle can be added to the respective nuclei with the help of pendular bridges, another possible ways, where two or more nuclei combine and form big nuclei. After completion of the phase, upon application of agitation to the bed the combined nuclei reshape and this phase can defined as a condition where large number of small granule present in greater range of distribution.

c) Ball Growth

When agitation continued, granule coalescence continue produce unusable, over-massed system where this phase greatly depend on the liquid quantity and material properties.

Coalescence

In this stage, two or more granule join and form large granule.

Breakage

Granules subject to break into fragments and this fragments adhere/join with other granule form a layer to the persisting/living granule.

Layering

Addition  of the new powder mix with the existing granules, the powder mix adhere with the existing granules and form a layer over the existing granule and increase the granule size.

Abrasion Transfer

If agitation applied to the granules bed, then agitated granule leave abraded materials, which further add to the other granules and accelerate the granules growth.

mechanisms of granule formation, ball growth

Factors Affecting Granulation Methods

Liquid Requirement

In high shear mixers, the liquid requirement margin is narrow to granule growth and produce over wetted mas. For the intensive wet mass and densification of the granule less liquid requirement assume compare to low share mixers. Impeller rotation speed is another factor for liquid requirements and resulting evaporation of the solvent specially water in the binder solution. In high-shear mixers, intense agitation results temperature rise and subsequently loss of solvent for evaporation.

Theory of granule formation in general

At the early stage of studies near at 1950’s, it was stated that the granules growth by coalescence and limiting moisture content and further mechanical agitation modifies granule shape.

mechanisms in the granulation process

The modern science has divided the process in four major class for granulation process such as-

  • Powder wetting and nucleation
  • Granule coalescence or growth
  • Granule consolidation
  • Granule attrition or breakage
  • Granulation is a complex combination of these subsequent processes.

Pharmaceutical Granulation Technology

The word “granulated” derived from Latin Word ‘‘granulatum,’’ denote “grained”. Granulated materials come from two way, by “size enlargement” of primary particles and “size reduction” of dry compacted materials. Now a day’s granulation technology has been widely applicate at mining, agrochemical and coal industry.

In these industries, agglomeration techniques mainly used to reduce dust and this technique provide easy handling and boost the material’s decisive effectiveness.

In the year of 1843, W. rockedon invent the tablet press and subsequent modification and patent was done by J. A. McFerran[1874], T. J. Young (1874), and J. Dunton (1876)  in USA which tremendously hit the granulation technology in pharmaceutical technology. The granulation technology was further reshuffle at 1970 when high speed tablet and capsule filling machine with PLC was invented.

The regulatory bindings such as content uniformity/blend uniformity facilitate to produce desired granule characteristics for pharmaceutical company. On the other hand, continuous uniform materials/granule flow must be ensure for high-speed compression and capsule filling machines. Granulation is the best example of particle design. The attributes of the granules controlled by formulation and the process respectively.

Granulation method can be divided into two major group as Wet granulation where liquid use to bind primary particles and Dry Granulation where no liquid is used.

various granulation techniques

The reasons for granulating a pharmaceutical compound are demonstrated as follows:

  • To decrease dust.
  • To densify the materials.
  • To increase the appearance of the product.
  • To simplify metering or volumetric dispensing.
  • To improve the flow rates and rate of uniformity.
  • To escalation the uniformity of drug dissemination in the product.

Processing steps of drug substance can be easily achieved avoiding granulation steps. By using a direct compressible excipients like MCC[Microcrystalline Cellulose] which was introduce in 1970s in a blender then compress tablets or filled hard gelatin capsule. This is very efficient method for cost effective method, faster process time and simple process steps.

In this technique, low dose of drug substance show reverse criteria, uniformity of drug substance is not possible/ accurate result may not found. The sample need to collect from the blender and time require performing the test to get satisfactory result. A newly introduce PAT[Process Analytical Technology], online measurement of ingredients made possible. FDA also release latest guideline about PAT.

Beside content uniformity, there are numerous cause to avoid direct compression technique for wide range of products where drugs substance need to densified to reduce size and physical criteria such as disintegration, hardness, friability need to meet.

Another approach like traditional spray-drying process become popular in day to day to produce drum to hopper granulation avoiding conventional granulation process.  This is very suitable for OTC drug which generally produce large amounts.

In pharmaceutical company, some of the products/drug substances are moisture sensitive which can’t subject to direct compression, then roller compaction is the best method to compress this product.

Before introduce of high shear-mixer, low-shear mixer was the first priority, shear-mixer generally use in in wet granulation their efficient, reproducible and modern process control capability. High-shear mixers enhanced with new technologies as one-pot processing and subsequent drying using gas stripping/vacuum or microwave.

The most versatile featured Fluid-bed processors has been using in the pharmaceutical industry over the last 35 years though initially it was introduce with single dryer, now enhanced with multiprocessor to coat particles, pelletize, granulate and drying. Now combination of high-shear mixer for granulate and fluid bed as dryer is the most popular method in granulation technology.

granulation techniques and processing

Theory of Granulation

Wet granulation technology is especially considered in size enlargement where small particles are compacted; agglomerated or else brought together to form larger particle comparatively permanent structure though the original particle can be distinguished. Size-enlargement and Granulation technology has the wide range of application in various industries like pharmaceutical, fertilizer and detergent production factory.

Granulation Process, theory of granulation in pharmaceutical company Read More »

ALCOA Plus and ALCOA its importance in data integrity

ALCOA Plus [ALCO+] is the most powerful and sharp compare to previously introduced ALCO has the great importance regarding data integrity in pharmaceuticals company. Data security is the provocative questions is the pharmaceutical and related healthcare sector. Adulteration of data leads to serious health hazard to the end user.

All of the regulatory authority of healthcare related sector has taken their active place against data Adulteration. Data must be accurate, No an Adulterate data is accepted at any situation. Everybody desire the right data at any time any place. Data violation define the serious non-compliance of GMP.

ALCOA is abbreviate form, which indicate Attributable, Legible, Contemporaneous, Original and Accurate. In the period ALCOA, extend to ALCOA Plus[ALCOA+] by addition of Complete, Consistent, Enduring and Available.

In previous time all of the GMP compliance company use ALCOA, now they use ALCOA Plus concept to capture its place the most dependable tool for data security. Most of the GMP oriented company taken the tool for data security and data quality. ALCOA Plus ensure the data security and Integrity. All of the major GMP authority choose ALCOA Plus and implemented their respective directive. ALCOA determine the all-out of data quality. UK MHRA, FRA, TGA, WHO purely involved in data security, quality and data integrity.

The ALCOA and ALCOA Plus concept has been illustrated for better understanding of data related matters.

ALCOA

1. Attributable

Attributable define that the data must be easily traceable, so that anyone can identify that a specific person has collect the data in define time and noted down correctly. To correct any type of error regarding data recording, correction to be made in such way that anyone can read the error data and the corrected data easily. Reason must be noted down with specific signature and date.

Any document subject to data recording must be contains specific field where anyone can note down his/her name then signature and date option. Specific must contains sufficient space so that anyone can record data easily. If any alteration required, put a straight line over the error data then write down the actual data with signature and reason. If space is not available the put an asterisk mask then put another asterisk in a place where sufficient space for signature and reason recording.

2. Legible

Most of document in pharmaceutical company subject to data recording in specific field of a specific document. Entered data must be readable. Data which can be easily readable defined as legible data. Unclear data create confusion to reader and result of a specific test or critical point create unwanted error. The personnel who are responsible to entered data must be trained on GDP [Good Documentation Practice].

Permanent ink or indelible ink to be use to record the data, ball point pen to be use instead of fountain pen. Different color ink to be use to identify the recorded data easily i.e. if the printed document is black color then blue color ink pen can be use to record the data. Similar color ink pen with printed document create delay to identify the specific data.

The input data must be clear and easy to traceable who is responsible to input the data. Data should be entered in such way that no visibility of data subject to misunderstanding to the reader. Anyone who is going to deal with the recorded data must be comfortable with it.

3. Contemporaneous

All the data subject to recoded in document must be recorded on time indicate contemporary data. All data must be entry on the specific field of the document, just after completion of the work with signature and date, if any error occur during data recording then GDP to be follow to correct the issue.

If any correction identified after recording of data in the later date then actual data to be entered data and time with signature on that date. No advance or later data entry is not indicate cGMP culture at your firm. On time data recording is the pre-requisite of the compliance.

A person on the specific date may be absent or leave or fall any unwanted situation, if he fail to entry the data cause serious non-compliance so in time data entry to be ensure. If require, a training session may be conduct to emphasize the importance of contemporary data. Contemporary data culture on the document define that your firm is up to date and ready to face any compliance audit both local and global.

4. Original

To protect the data integrity, the original record must be preserved in such way that it can be preserved till it expiry. Batch document and some documents to be kept additional one year from its product expiry but validation document lasts company life so all type of document preservation may not same. A policy to be develop to preserve the documents and record.

Some document need to duplicate in multiple copy, in this case the creator must ensure the authenticity of the multiple copy with the help of site quality head other that QA documents. A controlled copy seal may be introduce for this issue.

5. Accurate

All data subject to record in the document must be error free. Data can’t be change at any cost. Alteration of data is strictly prohibited. Print out any data create its accuracy, hand written or manually input data, subject to change or alteration. If any facility declare to print out option then manually input data is totally invalid. You must follow the machine print out. To maintain the data quality is the big compliance issue.

Alteration of any digit in manually define the serious discrepancy data quality. It is undesirable to may any digit to next digit or similar digit. Data rounding may be accepted as per USP method but it is not mandatory to follow.

6. Complete

If it’s declare that the data is complete, then it means no alteration, deletion, only original data has been taken from its actual documented time. Incomplete data create haphazard situation to identify the original. Incomplete data recording leads the false result. Data to be record at actual from its predefined time as mention on the document.

If any document declare that you have to record data in 45 minutes interval then you have to record the data at 45 minutes interval not 50 or 60 minutes interval. If you note/record data other than 45 minutes create incomplete/false data. This data is purely incomplete.

7. Consistent

Data must be consistent, chronologically arranged in appropriate time frame. Data should be record in in such way that any audit can rely on it. GDP practice is the best way to record the data. Series of data that is chronologically organized define the data is more consistent and reliable. A reliable data can face any type of GMP audit due to it provides best data integrity.

Most of the pharma company face serious non-compliance at regulatory audit for data integrity. If your firm confirm data integrity then you can create best GMP culture at your firm. To maintain data integrity is the prior conditions of the cGMP.  

8. Enduring

All type of material is not suitable for data recording, specific paper to be introduce for specific data recording. Data to be record in such material that it can be traceable after a period of time. Generally long lasting material use for data recording. You should take care about readability of data after a specific period of time based on its impotence.

Usually better quality paper use to record validation related document as its last till company life. Regular uses document like batch production record may be record in general usage paper as its last maximum 3 to 5 years including shelf life plus one year.

Document subject to destruction, proper recording to be marinated as it can be easily teachable. Approval must be taken before proceeded any type of destruction related activities.

9. Available

Data should be kept in a specific place where you can easily find it or it is available as when required. It should be keep in a secure place and access must be limited. List of personnel must be define to access the specific area. Data plays an important role when any organization want to take any decision based on previous history. By this time you have to make it available on that time so you have to keep it in right place. All type of future reference backed by data history so you must pay attention to secure your data.

This all about ALCOA and ALCOA Plus

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Technical person, How to become a Technical person

Technical person

Technical person, a person having STEM degree or person possess degree in lab-based science, technology, mathematics and engineering.

People who are attained STEM degree contain common set of traits. These traits make him ideal scientist, technologist, mathematician and engineer.

What do you mean by STEM?

STEM, this term often found in university advertisement, campaign, website, leaflet etc. but most of the people is not sure what does it mean. Here is the solution-

The term STEM define Science, Technology, Engineering and Mathematics and relevant subjects that are all under these basic subject.

Due to these subjects are not straight forward so series of subjects are undergo these subjects. Different terms are used in place of STEM as STREAM and METALS but the term STEM is more widely used.

Though these subjects are widely distributed but huge volume of vacancy found the respective field. From its beginning of STEM, various types of institutions are try to attract the students/people. STEM courses are the top most priority of the most of the counties to remove the shortfall.

STEM subjects the best option for the people who are searching for a longtime to be a resident to the other country/ immigration to expected country. This also beneficial for all type of students who want to study in higher level in different countries.

What are STEM subjects?

The STEM subjects [Science, Technology, Engineering and Mathematics] is not standalone, various type of subjects are closely related/derived from STEM so they are also STEM subjects. Here is the list of some STEM subjects-

  • Aerospace engineering
  • Astronomy
  • Biology
  • Biochemistry
  • Chemistry
  • Chemical engineering
  • Civil engineering
  • Computer science
  • Electrical engineering
  • Mechanical engineering
  • Mathematics
  • Physics
  • Psychology
  • Statistics

This list is far more extensive, the list will be more distributed based the basic criteria. This list my helpful for someone who are really searching for STEM subject and he will get som idea about the pattern of the STEM subjects.

The career prospects of some the subjects is more exclusive such Astronomy leads to the straight forward career patch than others subjects which tends to multiple career facility. Most of the STEM related subjects tends to more valuable sector such as Finance, Accounts, Aerospace, Cinema, Special Effects, Design and communications, Sportswear, consistency, Farming, Telecoms, Energy, Pharmaceuticals, Healthcare, Medical device etc.

What is the current situation in the practical field?

The history says, most of the STEM degree holders are male compare to Female. Introducing women in technical field is not satisfactory, the completion is less to female. More than Eight times male are more involve than female in STEM subjects related activities.

About 12% women are graduated in STEM degree; only 3% engage in practical field others are tend to alternative sector or stop to practice. The gender balance is dominant tend to pay gap in STEM field. More than 30% pay gab observed in in Australia at 2013. A remarkable initiative to be taken in this field to fill up the gender gap in STEM related subject.

How to become a Technical person?

Technical person

1. Take post-secondary science classes

To enter into the professional STEM subject program, two years of college education is required. Most of the STEM subject’s candidate take 4 years of post-secondary education and achieved bachelor’s degree before applying any Doctoral program. As a STEM subject student you have to meet the requirements of the respective organization to get admitted for Doctoral Program.

2. Pass the Admissions Test

To enter into any doctoral program you have to pass the specific test. The specific exam includes various types of questions such as writing, critical reading, quantitative reading, critical reading, different type of process based on your STEM subject including one writing prompt. Exam occur all around the year, at least six times a year.

3. Earn a Degree of STEM subject

After passing the required test, you can apply for for Doctoral program of STEM subject, it may take 2 to 4 years based on subjects. If you want to gain practical knowledge, choose a program with 1 year internship.

4. Cultivate essential skills

To be successful in your next professional life then think deeply about your subject oriented skills, initially basic computer skill is required to run various type of thesis program and assignment oriented job.

5. Attend In plant Training

If you want to work in a factory related job/any job, you can apply for in plant training. Various types of organization offer this type of facility. If you select a program with 1 year internship, please escape this step.

6. Apply for license to practice in your state

You may face to license process based on your state require requirement. To start your career as profession STEM subject oriented job, license is mandatory in most of the state. Here you may face a single or multiple exam to prove your competency of the respective subject.

7. Pre assessment for interview

An interview process may arrange where SME[Subject Matter Expert]/ Assessors may present to conduct an interview. Number of SME/Assessors may vary state to state.

8. Attend interview

A representative will call you to attend an interview session based on your application with specific time and place.

9. Complete required training

If you want to work independently then you have to complete several training program based on your subject. Most of the SYTEM subject holder choose one or two years training program and on the job training program to facilitate his professional activities.

10. Responsible Technical person

After passing the exam and complete the required training program you can work independently or you can join a suitable position in any organization where you can create a value for yourself.

Also Read:

Qualified Person, How to become a Qualified Person?

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Qualified Person (QP), how to become a Qualified Person?

Qualified Person (QP)

Qualified Person (QP), is mainly responsible to confirming/assuring the quality of certain batch of pharmaceuticals products. So this is very important that a Qualified Person (QP) must be in depth understanding of the pharmaceutical manufacturing, quality control and overall activities of the marketed products.

Qualified Person (QP), is the responsible person to certify a certain batch of pharmaceutical product prior to use for trail purpose or to send in the distribution channel for marketing.

This is not mandatory to understanding the manufacturing practice/process/procedure accurately but he must be understand the critical factors which may affect the critical quality parameters, safety and distribution/supply chain of the marketed products.

Qualified Person working area:

Most of the Qualified Person[QP] working in different pharmaceutical companies in various role mainly in product releasing activities but they also involve in national health sector, in such type of departments which hold different manufacturer authorisation to create various medicinal products mainly use in investigational purpose.

Qualified Person

How do I become a Qualified Person?

1.0 Find a sponsor

A sponsor to be find out regarding individual guidance, training, prepare for final assessment, sponsor reporting about your eligibility to act as a Qualified Person[QP]. The sponsor also verify your application form signature required in various section of the application form.

Eligibility of Sponsor:

The sponsor must be the member one of the three professional body [The Royal Pharmaceutical Society, the Royal Society of Biology and Royal Society of Chemistry] and he must a QP [Qualified Person]. If your sponsor fail to meet criteria, then the sponsors form must be countersigned by the QP [Qualified Person] who will responsible to acting this issue about your engagement.

The sponsor must be involve in practicing QP who is known to you and he professionally known you in qualified period experience[1 year for Pharmacist and 2 Years for other professionals]. If you didn’t manage it, then you can use a Quality Assurance Line manager provided the report and countersigned by a QP.

Your sponsor is projected to:

Confirm that you have the sufficient knowledge of the subject that covered by the study guide. Certify the adequate experience.

A sponsor is actually a mentor for you. He will help you regarding your preparedness of the assessment, he will guide you to attain your success. He will confirm you that you possess the sufficient knowledge for final assessment. He will trained you in every step for apply the final assessment. Your Sponsor will provide you the necessary study guide and confirm that you possess the essential knowledge, skill, experience and personal attribute to act as QP[Qualified Person] at actual.

Role of an active sponsor

Role of the sponsor is the key to success of the applicant. This is very important for the applicant to find out an active sponsor because a sponsor is always involve the applicant training and application process. A sponsorship is always appreciated if role and responsibilities perform on great care. Regular interaction with the applicant is very important and this activity will be consider as mentor.

The sponsor Form and the application form is the first step of assessment process due to these two forms provide the documented evidence regarding employee background. The well documented application provide the positive impression to the Assessors.

The sponsor must have the experience and knowledge about pharmaceutical manufacturing, Quality Assurance and GMP[Good Manufacturing Practice]. Well conversant and up to date of the legal framework of EU and UK. Better understanding and relationship with professional bodies of MHRA & VMD [Medicine and Healthcare products Regulatory Agency & Veterinary Medicines Directorate].

The code of practice, role and responsibility of QP to be known including Study Guide and practical experience requirements. It is top most priority to be well familiar with the pharmaceutical business especially in Research and Development, production, Quality, Marketing and distribution.

An active Sponsor must possess good inter-personal skills and well communicator, having good contacts outside the company will add extra benefit. A better Sponsor will work as mentor who will provide the guidance to the aspiring applicant including positive direction.

Regular interaction is the key factor of the success, sponsor may communicate with applicant via various type of communication method [FB Messenger, WhatsApp,SMS,Emailing etc.] if unable to direct contact. Sponsor should monitor the daily activities of the applicant and prepare a progress report.

Sponsor’s report

Before submitting the application a sponsor form must be submit with the application. An application will not accept/review without sponsor report. A sponsor report must be different from applicant, sponsor report may not represent the same as applicant form.

A honest review is always create positive impression to the applicant. A sponsor report well be well described about the candidate. Every single details will be mention here. Applicant strong side as well as weak side, strength, personal attribute, development field need to mention very clearly.

The report is a key part of the sponsor’s input and it is not sufficient for you to simply provide a declaration of belief that an applicant complies with the requirements. It should be a critical and honest evaluation of the applicant’s technical and professional knowledge. It should also include information on the applicant’s personal attributes, including his or her strengths and weaknesses or areas for development.

A sponsor may indicate the following criteria of the Applicant but not limited to-

  • Attitude
  • Communications skill
  • Extracurricular activities
  • Flexibility
  • Hobbies
  • Open Mindedness
  • Organizational behavior
  • Peer coworker relationships
  • Planning and organizing skill
  • Professional integrity and ethics
  • Problem solving capacity
  • Verbal skill
  • Reliability
  • Working under pressure

This very important to notify the every single points on the report. Application primary assessment may be late based on the points and further clarification may be asked. Sponsor need to confirm that the applicant has gained the proper knowledge and experience in the Manufacturer’s Authorization and Manufacturer’s Authorization number with issue date to be mention with the application. A sponsor must declare the direct the working experience with the applicant. Different report will claim for multiple establishment.

2. Gain relevant experience

To be a QP[Qualified Person], a person shall be possess a certificate, diploma, or other evidence which can prove his formal qualification evidence which achieved after completion of University course, covering a duration at least Four Years of  theoretical and practical studies one of the listed scientific discipline:

  • Chemistry
  • Medicine
  • Pharmacy
  • Pharmaceutical chemistry
  • Pharmaceutical technology
  • Pharmaceutical biology
  • Veterinary medicine

The minimum duration of the university course may be three and half year, where the course followed the theoretical and practical training duration minimum one year and training period will be six month in a pharmacy open to public collaborated by examination at university level will be preferred.

When two university course declared equivalent and one course extend to Four years but other course extend to three years then the three years course will be treat as diploma, the course shall include the listed basic subjects at least:

  • Analytical chemistry
  • Experimental physics
  • General and inorganic chemistry
  • General and applied biochemistry (medical)
  • Microbiology
  • Organic chemistry
  • Pharmaceutical chemistry
  • Pharmacognosy
  • Physiology
  • Pharmacology
  • Pharmaceutical technology
  • Toxicology

The QP[Qualified Person] experienced in practical required two years in authorized manufactures  and experienced may be reduced to One Year where the university course extending to Five years.

Overall, at least Two years expected is required in one or multiple facility which produce medicinal products but if you are pharmacist, you need only one year.

3. Apply through your professional body

The eligibility of QP, he must be the Pharmaceutical Scientist or Associate or Fellow or member of RPS[ Royal Pharmaceutical Society] who has qualified on the basis of formal course of study lasting not less than three years in fulltime or equivalent.

Minimum One year of practical experience is required for pharmacist, if anyone want to apply for QP eligibility but not registered a as pharmacist recommended to contact with QP officer for advice prior to apply.

If your Sponsor is satisfied that you are ready to apply then submit the application form with required fee [£700, may be change anytime], sponsors report and countersigned copy of your own certificates.

4. Wait for your initial assessment

If you application fulfill the requirement then QP officer will confirm you that your application has been received. Your application will be assessed be the designated assessor if the result goet to positive then you will be invited for interview session.

5.0 Attend your interview

Your interview will be held on London physically if situation is normal. Sometime virtual interview may held based on situation, QP officer will confirm you about this issue. If you passed the interview then you will be listed as QP person at your professional body.

Qualified Person

Role and responsibility of QP

All of the pharmaceutical manufacturing authority and regulatory body ensure that the end user [Patients] are safe and the medicinal products meets its predetermined specification for sale or supply and confirm the basic requirements for safety, quality and efficacy.

  • In a pharmaceutical company a QP plays a vital role certifying the batch confirms the predetermined specifications and its can be released for sale or supply or trial.
  • QP is responsible to confirm that each manufactured batch has been checked in compliance with the laws in specific certifying authority.
  • QP role and responsibility irrespective where the product will be sale/distributed/used.
  • QP to be understand the demand of specific Authorization and confirm that PQS[Pharmaceutical Quality System] in place and satisfactory for the purpose.
  • QP must understand the relevant steps of pharmaceutical manufacturing steps before certifying the specific batch.
  • Must be full understanding of EU GMP guideline.
  • QP must have decline to certify the specific products which process and procedure is unknown to him.

Career​​​​​ prospects of QP

The Career​​​​​ is widely distributed for the QP in various types of pharmaceutical industry as well as other designated industries who are involving in manufacturing of healthcare related products undergo to regulatory bindings. In pharmaceutical industry a QP can work in production, marketing, quality control, product development, quality assurance, project management etc. areas.

Resources to become QP and formal application process

Application form

Guidance notes for applicants and sponsors

Study Guide

Code of Practice for Qualified Persons

Sponsor Form

Download all Resource Here:

Click Here

Qualified Person (QP), how to become a Qualified Person? Read More »

Ten golden rules of GMP, what do you mean by it?

Ten golden rules of GMP

1.0 GMP Golden Rule-1

Get the facility design right from the start

All the manufactures who are engage to produce Foods, Drugs, Medicine, cosmetics and other healthcare related products want to follow the all basic rule of the GMP/cGMP. This is to be stated here that the compliance of the GMP is very much easy to follow if the facility design perform right way from the start.

To run a smoot operation, this is very important to follow the principles of GMP as well as  First Golden Rule of GMP Get The Facility Design Right From The Start”.

“If facility didn’t design right way from the first then you may fall in great problem and may be reconsider the whole facility design”

Facility Design

There will be a healthy harmonization between the sequence of facility design where the main target of the facility design is to reduce the mix-up, cross contamination as well as smooth production process. You can’t allow blister packing room near raw dispensing area. The area must be design as such a way that change of non-compliance can be reduce.

A well planned facility design may reduce the overhead of production and least change of product failure. This also prevent back flow and increase productivity to the respective firm. The aim of the best facility design is to –

  • Lest traffic movement at the production area.
  • Align the material in specific room/area.
  • Reduce contamination/mix-up of the products.
  • Minimize the wrong interpretation.

The target of the good production design is to continue the linear production area so that man and material flow will be unidirectional no backflow the same. The Zigzag and irregular design of the facility tends to misinterpretation of the production design and design failure exhibit predominantly. To apply/introduce/change the existing facility design must be review the SME [Subject Matter Expert].

Environment

This is very important to control the water, lighting, ventilation, temperature, humidity, air etc. so that the respective variable can’t effect the product quality, safety, and efficacy. So the facility must be design must be precisely and risk of non-compliance can be reduce.

A suitable facility must be confirm-

  • Temperature, Humidity, Pressure, light is appropriate to the standard practice.
  • The surface of the wall must be free from all types of crack/dam/swelling/dust/rust etc.
  • Wall must be design in such a way so that it can be clean easily.
  • All type of drainage must contain 1% slope so that the backflow can be prevent easily.

Equipment

The equipment to be locate, design, install, operate, in such a way so that the intend use can be confirmed to its standard. A standard equipment should be-

  • Well designed, properly installed, easily operable and easily cleanable.
  • Easily usable
  • Properly labeled
  • Not reactive with the product
  • Rust free
  • Calibrated at specific interval
Ten golden rules of GMP

Ten golden rules of GMP

2.0 GMP Golden Rule-2

Validate processes

After design the full facility and equipment of a farm, this the mandatory rule that you must ensure the machine and the facility are operate to its standard but how do you prove this state? Now the term Validation come here first.

Documented evidence is mandatory to prove that the process and equipment doing its own function they supposed to do. To achieve a quality product the consistent function of the machine is essential and this activities can be achieved by effective validation of the process and equipment.

Validation

The validation is the documented evidence which provide the high degree of confidence that specific process will consistently produce a specific product meeting its previously approved specification and related quality parameter.

The validation is the GMP requirements which prove that a specific process, equipment and facility operates right way from the first time to every time without any significant change. The new facility, equipment, process need to validate prior its regular use. Any significant/substantial change in the existing validated system need to validate the system/process/equipment etc.

Ten golden rules of GMP,  Type of validation

Validation usually involves:

An equipment/machine generally undergo the several process to complete its validation status. IQ[Installation Qualification] confirms that a specific machine/equipment has been installed correctly to its predefined specifications mentioned its approved IQ protocol.

OQ [Operational Qualification] confirms that the equipment has been successfully installed and operate to its specification mention its approved OQ protocol.

PQ [Performance Qualification], confirms that a specific machine/equipment can produce a product to its predefined specification mention on its approved protocol.

The above all protocol mention the specific process steps, one the work completed successfully a report must be generate to prove the specific activity.

Change control

After completion of the validation programme of the system/equipment/machine/process the maintaining the validation status is important. Once the change is made in any part of the validated facility subject to change control process. A formal change control process must follow to control the whole system. A substantial/ significant change subject to revalidation the system and record must be keep the same.

If a process/part of process/part of the equipment subject to change which may affect the quality of the product need to record keeping through change control process so that the respective firm may overcome regulatory bindings.

Ten golden rules of GMP

3.0 GMP Golden Rule-3

“Write good procedures and follow them”

It can’t be imagine a good company without proper written procedure. An unwanted situation may arise to repeat the specific job from memory. Most of the manufacturer of the firm rely on the experienced operator rather than new one.

This is very logical than an experienced person is always expected to perform the right job but it is not possible to memorize the right job every time may be forget to perform the any specific critical steps resulting failure of the product.

This is the best practice to write down the whole process at actual which perform on the machine/specific stage.

A firm must be document specific not operator specific.

In a foods, drugs, cosmetics industry this is very important that the specific procedure must be clear, concise and logical and must be in place so that anyone can trace and realize it when required and this is the important part of the GMP.

You may consider the SME [Subject Matter Expert]/Third Party Audit Team/Experienced Existing Professional to develop your documentation. When an independent team/party/organization audit your firm they will develop your documented activities and find out your loop hole of the specific process/ procedure/stage and then you will get the huge opportunity to develop it.

List of documents require for standard Firm:

A typical Firm [Foods, Drugs, Medical Device, cosmetic industry] contains the following document but not limited to-

Standard Operating Procedure: Describe the details written procedure/instructions/process to complete the specific task where relevant.

Product/Materials Specification: This the core of the product/Materials which have to confirm/meets to evaluate its quality attribute.

Records Keeping: This state provides history/executed option of the certain products/materials that the products/Materials are following its predefined approved criteria and repeated the criteria each time when produced.

How to write good procedures:

First of all, before writing a good procedure you have to read the all relevant document then start write the main procedure. Use small breakdown of the large paragraph and use Flow Diagram, Chart, Table, Keyword, etc. for precise and easy understanding.

Generally, people don’t have the much time to read the whole procedure from the start to end; want to eye through the whole procedure on the keyword.

A critical/Big process/ procedure can be divided several small things as-

  • Bold Text
  • Bullet Points
  • Charts
  • Follow Diagram
  • Heading
  • Highlighted Text
  • Image
  • Instructions
  • Table

This type of activities reduce the man hour as well as easy understanding the documented evidence. Write down the language in very easy process, where required mother language rather than English use the same for better result. Don’t include extra paragraph for a little information. Write down the whole process in imperative sentence. An ambiguous word mislead the information; so use easy word that is more familiar to everyone.

Use as many simple sentence as possible so that anyone can read it easily. You can follow ALCOA[Attributable, Legible, Contemporaneous, Original and Accurate] and ALCOA+[ Attributable, Legible, Contemporaneous, Original and Accurate with Complete, Consistent, Enduring and Available] method to create a better legible document.

ALCOA and ALCOA Plus, Ten golden rules of GMP

After creating an initial document, printout the same and handover this copy to the relevant personnel and collect the feedback from the personnel and request them to notify which part of the document is confusing and hard to understand the main content of the document.

Mark this section and review the document and apply the correction to the document then you will able to create desirable document for the relevant personnel. This is the method to make a simple standard document but not limited to, you can apply various methods to generate a better documents. 

A crated documents need to review it’s periodically to keep it up to date. Most of the company review their document at a Two/Three year’s period. You can review the document yearly or anytime when the relevant topics change based on the available/reliable approved information. Without strong reference/approved information, changing a document create hassle to the existing system.

Follow the written procedures

This is the best practice to have the better written procedure at the place in controlled manner and everyone is following it. A document may be descriptive to the specific process/procedure where alternative/shortcut process/procedure may save the time or you can do it efficiently. Don’t do that.

Do the thing what is written on the document, if require any change, notify the respective authority/your supervisor/Head of Site Quality Person about the issue. Change the document through change control process and until change the document you have to follow the document due to your proposal may not accept if critical change require to apply the proposed change.

You can’t apply your proposed change without approval, due to-

  • Your process/proposal may not be cost effective in the long run.
  • Each validated steps/procedure/process has its importance which change may affect the product quality/efficacy/safety.

Ten golden rules of GMP

GMP Golden Rule-4

 “Identify who does what”

Every employee must have the clear, precise, specific responsibilities to the respective department. He must know what he supposed to do or what not his responsibility. The specific responsibility will reduce the man hour and better working environment. Every department of the firm must have job description of their employee. A typical job description will contain the specific point such as-

  • Job Title
  • Duties and Responsibility
  • Experience
  • Total Service length
  • Service length of the existing firm
  • Core Responsibility
  • Additional Responsibility
  • Administrative Activities
  • Special Responsibility

The responsibility must be stand alone. No overlapping isn’t acceptable. Doing similar job by multiple employee cause serious misunderstanding and job undone. Better to display the everyone responsibility on the firm notice board at specific department will show that who does what. The cross functional department will easily contact with the responsible personnel if job description available on intranet/sharing folder/common FTP sharing within the firm.

The responsibility may be overlap in the following cases but not limited to-

  • Calibration Activities
  • Cleaning Activities
  • Validation Activities
  • IPC in multiple section
  • Production activities
  • Analytical Activities

Before assigning a specific task for a specific employee, he must be train first and a mock test will be perform before final certification of the employee. An employee must confirm that he is capable for the specific job.

Especially critical activities like Validation of the specific product/process/facility, a series of work to be done precisely without any significant non-compliance, then a person must be assign who is capable to perform the series of task with great responsibility.

Ten golden rules of GMP

GMP Golden Rule-5

“Keep good records”

A good records determine that your system is under control and you are compliance with the GMP which also demonstrate your visibility in terms of quality matters. A good records exhibit that you have followed the all steps and activities describe in the batch production history from dispensing to finished products. This is the part and parcel of the GMP to keep the good records of your production activities.

How to keep Good record?

Make a culture to keep the good record in daily activities. Never try to memorize the activities. Keep your record up to date on the right time at right place.

  • Don’t perform any type of activities which you are not responsible for or you don’t have proper training to do the same. If you think that the work has been completed without proper documentation then you are in wrong concept. If you are unable to record the activity then it didn’t happen!!
  • Try to develop less signature option at your document, unnecessary signature creature signature fatigue to the employee.
  • Record all types of activities carried out during production.
  • Never try to memorize the activities, record it on time.
  • Record all type of activities if deviation occur, then inform the Site quality department and take the decision for the same.
  • Record all type of record in legible ink. Signing any type of record reveal that you are accepting the described activates.
  • Notify all type of mistakes drawing a single line and write the actual, give the date with sign and mention the reason for the correction.

Documents Record Keeping

Generally you should keep the record of all documented activities. Some important records are-

  • Analyst Personal Analytical Logbook
  • Batch Production Records
  • Cleaning/Equipment Logbook
  • Cleaning/Equipment Logbook
  • Environmental Monitoring Records
  • Material/Product storage condition records
  • Training Records of Employee

Keep the validation/calibration records life time of the company. Keep batch/production record for expiry date of the product with additional one year. After expiration, keep record for destruction of the document and you can take critical data from the expired documents on validated spreadsheet for further reference. You can keep your document as per your own define period.

Ten golden rules of GMP

GMP Golden Rule-6

“Train and develop staff”

If a firm is properly equipped with the right tools then consider the skilled employee to operate the machine. Document the activities through proper training before starting any type of commercial activates in a validated facility.

Every personnel of the firm must be trained before assigning any type of job. Confirm that the respective personnel have the desired skilled and capability to perform the right job at right time in right place. If you able to do the same then you can develop the GMP culture at your firm.

Training

First of all you have to train the all personnel related to production activities, Laboratory Activities, Quality Assurance activities or whose activities directly affect the quality of the product. Some basic training need to include their training curricula. A training need assessment to be arrange before engaging someone at specific duty.

training type, training method, Ten golden rules of GMP

Some training is common for all employee such as basic GMP training, personal safety and hygiene, Fire Fighting, emergency evacuation plan etc. to be include to the personal training profile.

If any situation occurs, where you have to allow someone to enter the specific area like production then you have to give him some instructions what to do or what not to do, additionally assign a experienced person with him for close monitoring purpose.

Train the employee as relevant as per job description, unnecessary training cause haphazard situation. Identify the group of employee for common training curricula will save your valuable time. Arrange the training as when required.

After completion of the training program certify the employee for specific task and record the same. Initially you may follow up the new employee with the close supervision of a senior experienced skilled person. If everything goes well then give him signing authority to the respective document.

Verified job capability

An employee must prove his job competence during everyday activities producing quality products/documents. After proper training of the respective employee, he must be prove himself that he is very much capable to do the same from the first time to every time in right way.

If he fail to do the specific job then arrange retraining for the same topic then involve the same. If any employee fail to do the same job in several times after retraining then change his job description to the next available job responsibilities.

You can assess the employee through annual appraisal plan, taking record for good/poor activities and discuss the employee with his week point and try to develop it. You can discuss a series of topic with the respective employee-

  • Attractive compensation package
  • Bonus/Festival Bonus/Daily Allowance/Overtime Package
  • Current position Analysis
  • Departmental plan
  • Document the poor records
  • Foreign Training/Foreign Tour/Local Tour
  • Gift hamper/Family day/Tour/Annual Picnic
  • Insurance Plan/Group Insurance Facility
  • Responsibility Analysis/Remind his responsibility
  • Roles and responsibilities

Record Keeping

You must keep the record of all training record of the specific employee including retraining record, evaluation of the specific training at his training record file in a traceable place. A training coordinator to be available to monitor the training activity of the firm.

A person from every department will be responsible to communicate with the training coordinator regarding departmental training activities. Training coordinator will arrange the all type of training of the respective firm.

Ten golden rules of GMP

GMP Golden Rule-7

“Practice good hygiene”

Product contamination will be at higher level if proper hygiene and sanitation program is not maintained. Cleanliness is the key factor in the pharmaceutical industry due to some products like Injections/Infusions are directly administer to the blood stream, if products are contaminated/compromise with pyrogen then any one can face moderate to serious health hazard.

personal hygiene, Ten golden rules of GMP

A Standard Operating Procedure [SOP] to be develop regarding hygiene and sanitation. The procedure to be maintained from the first time to every time before starting any type of production activities. A better hygiene practice can develop better GMP culture at your firm. Every employee must confirm to the sanitation and hygiene procedure.

Good to practices in everyday manufacturing-

  • Maintain personal hygiene everyday by wash your hand, wearing protective gloves, head cover, beard musk, protective musk, hand sanitizer [70%IPA] especially when you are in production area as when required.
  • Notify your senior/supervisor/authority/Department in-charge/Manager if you are ill/having open wound and probably you are not allowed to manufacturing are till you feel well.
  • Less/Minimum personnel to be allowed at direct manufacturing/filling area and less product contact to be your first priority.
  • All type of Eating/Drinking must be prohibited at any type of production/packaging area.
  • Cleaning and sanitation instructions to be hang on different area of factory premises to increase awareness regarding this issue to the existing employee.
  • Visitor/Outsider/Auditor Entry to be prohibited to the direct production/manufacturing area.
  • Notify any type of non-compliance to your Superior/In-charge.
  • Before starting any batch, remove all type of waste, dust, excess materials except relevant materials.

If possible arrange a personal hygiene and sanitation training program in each month. A schedule may be prepared for different department if it not possible to cover all employee in single time frame. Schedule to be organize in such way that every employee get training at least once in month. If this procedure can develop then you can hope that your firm is conforms to its GMP compliance.

Ten golden rules of GMP

GMP Golden Rule-8

“Maintain facilities and equipment”

Maintenance schedule must be established to facilitate the activities of the daily work. A regular maintenance activities reduce the sudden machine failure during production. Maintenance activities also reduce the product contamination.

A maintenance schedule to be followed effectively and supporting machine parts, oil, coolants, Lubricants, grease, Mobil etc. must be available to continue the activities. Maintenance schedule must be available in place and authorized personnel to be assigned to perform the specific job.

Ten golden rules of GMP, classification of maintenance

Maintenance Logbook:

A maintenance record must be keep in a specific form and store the same at the custody of maintenance department and must be traceable as when required. Maintenance trend to be done in monthly/yearly basis to identify the machine breakdown frequency and corrective action.

You may use maintenance Logbook for better documentation activities. A maintenance logbook generally contains-

  • Activities performed
  • Clean date
  • Calibration date
  • Equipment use date
  • Last maintenance date

Ten golden rules of GMP

GMP Golden Rule-9

“Design quality into the whole product lifecycle”

Personnel engage in Foods, Drugs, Cosmetics, Medical Device Manufacturing company to aware about the safety parameters of the end user[Patient]. Final stage of the products are tested by the Quality Control Personnel to identify/confirms its predetermine specifications only so quality to be ensure all the stage of manufacturing prior marketing in whole product lifecycle.

product life cycle

An inferior quality products tends to degrade in market in a short period of time loss its potency from marginal level fail to confirm its intended use. Patients didn’t receive the desired effect, unable to get early recovery cause unwanted health hazard. The patients start to believe that the product is not fit for him as its fail to satisfy his basic need.

The manufacturing step of the product need to effectively control so that a product can achieve its desired quality parameter through its life cycle.

Checking and Testing of Incoming Materials:

Check all the incoming materials during receiving and sort out the damaged container at specific area to prevent mix-up. Attached “Quarantine Label” to the good one and store it Quarantine area and inform Quality Control Department for Sampling and next activities after completion of Warehousing Activities.

Collect Approval from Quality Control department then use it for manufacturing activities. If the sampled products fail then segregate it and store it Reject Area for further decision[Destroy/Return]

A checklist may be develop to check the basic parameters of the incoming material will prevent the missing/discrepancy of the materials. Purchase order number, material description, quantity, accepted, conditionally accepted, or rejected materials etc. parameters may be add the Checklist for Inspection of Incoming materials.

Manufacturing Process Control

A series of procedure to be perform at the manufacturing of a specific products. Process and procedure must be clearly defined on the Batch Manufacturing Record and the personnel engage in manufacturing activities must be trained properly. A GDP[Good Documentation Practice] to be develop to practice on time record keeping.

Approved master record to be develop and available in a secure place. A batch record must be represent the master record and update document to be issued prior its intended use. All data must be input on specific area of the batch document. All actions must be record including all QMS[Quality Management System] related activities. Specially cleaning activities during/prior batch manufacturing must be record.  

Batch Packaging and Labelling Activities

Labeling is the vital part where maximum chance to mix-up of the products. Printed Label to be store securely especially in cut label/single label. Printed label to be store as per batch number/lot number to assure traceability.

Before starting a new batch, all the materials in previous batch must be remove from the packaging line. Follow the Line clearance procedure describe in Batch Manufacturing Record. Record the all activities during product change over and time interval to be define for In Process Control action.

Ten golden rules of GMP

GMP Golden Rule-10

“Perform regular audits”

Internal Audit/Self Inspections to be performed before a face any type of regulatory audit. External regulatory bodies Like UKMHRA [Medicines and Healthcare products Regulatory Agency], FDA [Food and Drug Administration], and TGA [Therapeutic Goods Association] will conduct audit. A self inspection checklist to be prepare and self inspections/Internal Audit to be perform at least once in a year, multiple times in a year may be the best practice.

Self-Audit Checklist

Written Procedures/Specification

Is approved procedure clearly defined the step by step instruction?

Do the procedure follow by the employee?

Is the procedure is up to date?

Is everyone is strictly adhere on the approved written procedure?

Skill

Is everyone is properly educated, trained, experienced in relation to their job?

Is everybody is performing their job right way?

Documentation and Recording

Is document is properly recorded on time?

Is everyone is using legible ink as required to fill the document?

Is all document/critical steps are checked/double checked?

Sanitation and Cleanliness

Is personal good hygiene is in practice?

Is gowning system is properly defined on production/Laboratory?

Is clean equipment’s/machine is stored properly?

Is regular health checkup is in practice?

Maintenance of the Workplace

Is scheduled preventive maintenance perform on time?

Is environment is controlled to minimize product contamination, mix-up, error etc.?

Is equipment logbook is properly maintained?

Quality Control

Is everyone is clear regarding quality control and quality assurance activities?

Is right batch number is declaring from QC department.

IS sampling is properly done & sampling SOP is up to date?

Is all machine calibration up to date?

Quality Assurance Are we concern about quality of our product? If satisfactory result didn’t get then take initiative to implement the same. All audit must be take positively, this the process where we can find our quality related observations and we can update the same.

This is all about the Ten golden rules of GMP which is mandatory to follow for successful operation of an ideal pharmaceuticals. The Ten golden rules of GMP define the ten different areas of a Pharmaceuticals company so this is very crucial to follow Ten golden rules of GMP to develop GMP culture of your firm.

Ten golden rules of GMP, what do you mean by it? Read More »

In plant training report, how to prepare a effective report ?

In plant training report: the in plant training is the short duration training programme especially 2 to 4 weeks where the students get the practical knowledge about the industry really doing and what is happening in real life. The in plant training is very important for industry based students like Engineering and manufacturing like pharmacist, chemist etc. The training depends on the where you are face it. All industry/company doesn’t provide the same opportunity though they are similar. Rules, regulations, facility may be slightly different from company to company.

This article has been designed to give the basic idea about the pharmaceutical company manufacturing process and supporting department activities in pharmaceutical company. This in plant training report has describe the basic function of the company. This may be helpful to prepare a plant training report- A basic in plant training report consist of the following thing-

About XYZ Pharma Ltd.

The State of the Art manufacturing facilities of XYZ Pharma Ltd., is located in 117 Adams Street, Brooklyn, NY 11201, USA. The total land area of this site is 35 acres.

The manufacturing site is built with strict compliance to WHO cGMP standards and also to meet US FDA and UK MHRA requirements.

Delivering XYZ’s core values through a responsible approach to business by introducing differentiated medicines that make a real contribution to the health sector of USA, XYZ also aims to create enduring value for the society, and deliver a sustained financial performance that will match the best in the industry.

XYZ Pharma Ltd. is also committed to delivering new, medically important and commercially successful products to the market every year. Along with its commitment to competitiveness and high performance, XYZ will continue to be led by its core values to achieve sustainable success.

XYZ Pharmaceuticals Limited is the only company in USA having five separate and dedicated facilities on over 35 acres of land for the manufacture of variety of formulations like Human Insulin, Low molecular weight heparin, Cephalosporin, Penicillin, Ophthalmologic, SVPs, Dialysis Fluids and LVP etc. Besides its regular formulations like solids (Tablets, Caplets, Capsules), liquids (Syrup, Suspension, powder for suspension), creams & ointments.

PPL is committed to the best use of available technology and expertise of the time and thereby ensuring continuous improvements with regards.

XYZ Pharma Limited have introduced a new business division besides human health care is Animal Health Division which is committed to serve the best and becoming a leader in Veterinary Medicine sector in this country .

XYZ Agrovet the world-class healthcare solution provider, is one of the leading and fastest growing Agrovet company of USA, which is engaged in the manufacturing , sales & Marketing of a wide range of therapeutic drugs in the country through own distribution network.

Agrovet Division has launched its journey to helping millions of lives for the better through providing access to safe, effective and affordable veterinary medicines and related services to the people who need them. We have a leading portfolio of medicines that prevent, treat and cure diseases across a broad range of therapeutic areas, and an industry-leading pipeline of promising new products in areas such as infusions, Hormone and vaccines.

We know that we can best ensure the quality and innovative medicines in Veterinary medicine sector in USA . XYZ Agrovet Division offers information and support to help better understand the medicines to Veterinary doctors may prescribe as well as the farmer can be benefited with profitable Dairy, Poultry or fish farming.

Mission: Is to achieve business excellence through quality by understanding, accepting, meeting and exceeding customer expectations. XYZ follows International Standards on Quality Management System to ensure consistent quality of products and services to achieve customer satisfaction.

Vision:XYZ built on the foundation of providing the highest quality products aims to be among the top echelon of animal healthcare companies across the world servicing the needs of every animal sector.

The huge production capacity of XYZ Pharma Ltd. is now being utilized for its own product portfolio and contract manufacturing of specialty products for fourteen leading pharmaceutical companies of USA.

Following Pharmaceutical companies manufacture their specialty product in the state of the art manufacturing facilities of XYZ …………

Objectives Our Internship

To enrich the practical knowledge of the students, the university insists the students to offer the in-plant training. Such in-plant training will provide an industrial exposure to the students as well as to develop their career in the high tech industrial requirements. Reputed companies are providing in-plant training to the students.

This In plant training report is generally a practical work or a project work. Students are deputed to various industrial / research organizations based on various subjects of interest allotted by their respective institutions. This practical training helps students to understand industrial and outside environment. In other words, this acts as a bridge between academic institutions and industries for various job opportunities and building future professional careers of students after completion of their degree.

Among the professions of pharmacists like community pharmacy, institutional pharmacy, whole sale pharmacy, industrial pharmacy, government service, organizational management in our country industrial pharmacy offers great opportunity to the pharmacists.

So an industrial pharmacist should have proper knowledge about drugs and also about medical progress, commerce marketing and technology. To be a pharmacist beside academic knowledge, practical knowledge is essential.

This is why after appearing the Bachelor of Pharmacy examination in-plant training was arranged by the department in renowned Pharma industries. This training has increased our academic knowledge what we learnt in the last four years. We have completed our training in XYZ Pharma Limited a fast growing Pharma company in USA.

Description about the different area of pharmaceutical company-

In plant training report of Warehouse

Warehouse is an important part of any Pharma. Warehouse in pharmaceutical manufacturing plant or pharmaceutical factory is the place where raw & packaging material or spare parts of machineries are stored after import up- to go to production and from which the raw & packaging materials are delivered to the dispensing unit as per requirement for the smooth production and last of all, from where finished products go to distribution department from production unit for distribution to the market. Warehousing is normally the largest operation in the plant in terms of area and special attention should be focused on maintaining cleanliness, freedom from infestation & orderliness. Warehouse should be maintained within acceptable temperature & humidity limit.

Main Function of Warehouse

  • Receiving in-voice and purchase order from material management
  • Receiving materials
  • Cleaning of received materials
  • Weighing of received materials and compare with purchase order
  • Dispensing of materials according to DOS for production
  • Receiving of finished goods from production
  • Inventory of tool manufacture also maintains by warehouse
  • Documentation

AREAS OF WAREHOUSE

Quarantine Area

After receiving, raw materials and packaging materials are kept for QC approval in a yellow marked area

  • Materials come through a covered van and unloaded and cleaned to make it dust free.
  • Then these materials are checked individually and information like name, manufacturer, manufacturing date, expiry date, quantity and etc. are recorded in the checklist.
  • They are weighed and crosschecked whether they contain the same material and quantity as mentioned in the container or not.
  • If it is found to be up to standard then MMR (material receiving report) is prepared and materials are kept in the quarantine area for QC (Quality Assurance Department) approval

Released Area

QC approved raw materials and packaging is generally stored in the central place of warehouse with great safety and with controlled temperature and humidity.

  1. MMR is sent to the Quality Control Department; officer comes for sampling after receiving the MMR and sampled sticker are sealed. [If the receiving material is an active ingredient then 100% sampling is necessary but if it is, an excipients then (n+1) is done.
  2. If the sample is found to be standard by the Quality Assurance department then released sticker is sealed and stored in the central place of the warehouse with great safety.

Dispensing Area

One dispensing officer always responsible for dispensing the materials to the production and packaging materials to the packaging areas, following things must be checked by the dispensing officer

  1. Only released (green tag) materials are brought to the dispensing area.
  2. The dispensing area is completely free from materials of other products.
  3. Correct quantity and approved qualities of materials are being dispensed as per requisition.
  4. Materials that expired first are being dispensed first i.e. to follow FIFO.
  5. Documentation of dispensing

Finished Product Area

  1. Finished products are also stored here for delivery.
  2. Warehouse deliver the finished products as per asked by the planning department.

Rejected Area

  1. If the materials fail to pass QC test, QA give rejected tag (red tag) on each and individual container or box.
  2. Rejected materials are placed in the rejected area until further decision for final disposition is made (official letter is sent to respective department).

Packaging Products Area

Imported packaging products are stored in a separate room beside the raw material storing room in the warehouse with great care.

Special Area

This is a special room or area for stored light & heat sensitive materials like colors, flavors, vitamins poisonous materials, flammable materials etc. in maintaining temperature in between 20-25ºC.

QC Sampling Room

In this separated and lab- based room, when a new material arrives in the warehouse QC officer comes here for sampling test.

Change Room for Warehouse Officers & Workers

When any officer or worker works in the warehouse, before entering in the warehouse, he or she change his/her cloths here & wears apron, shoe cover and head cover.

The main functions of Warehouse:

  • Material Receiving
  • Storing
  • Dispensing

Materials Receiving System:

  • Upon receiving the shipment’s labeling should be carefully checked to make sure that they belong to the same batch. Only materials from the same batch receive the same Good receiving Note (GRN) number. The GRN is the identification number for that raw material.
  • The shipment should be inspected visually for damage.
  • The materials are than carefully labeled ‘Quarantine’ with the GRN number.
  • Rejected materials should be clearly separated from the ‘released’ materials.
  • Rejected packaging materials containing the company’s logo are destroyed. For raw materials that are the rejected the vendor is contacted immediately.

Storage:

Raw materials and finished products are stored according to their chemical or physical properties. Some raw materials and finished products are kept at normal room condition.

In order to prevent mix-up of printed containers and labeling materials, each printed packaging material is stored properly identified with the specific GRN number and code number and at the time issues the identity is checked very carefully.

Dispensing:

Dispensing means the materials are supplied to the production areas by weighing according to the proper document and release it from the RM store.

Close attention is paid to dangers of cross-contamination. Dispensing of raw materials is done in the presence of authorized personnel from production and QA.

The remaining stock is recorded to make reconciliation of the stock possible at any time. Dispensing is done under laminar air flow to minimize dust generation and microbial contamination.

Sampling:

As the process of taking a small portion from a lot for test and analysis to show the quality of the whole lot. The purpose of sampling and subsequent testing is to provide an effective check on the quality of the product or substances being processed.

Materials sampling plan:

The materials sampling plan done on the basis of FIFO system i.e. first in first out. For active ingredients every container and for excipients √n+2 containers are sampled (where n = total number of containers).

For raw materials stores:

  • Receives raw material according to the invoice/challan.
  • Takes GRIR from the Q.A department.
  • Updates the present status of raw materials.
  • Stores all raw materials according to the instruction.
  • Supplies raw materials according to the FIFO to the production floor.
  • Adjust present stock after dispensing the raw material.
  • Find out raw material that requires re-test.
  • Find out under safety stock.

For packaging materials store:

  • Receives packaging materials according to the invoice/challan.
  • Takes GRIR from the Q.A. department
  • Inputs the batch number.
  • Store all the packaging materials according to the storage guide.
  • Updates the present status of packaging materials.
  • Dispense packaging materials according to the requisition from production area.
  • Adjust present stock after dispensing the packaging materials.
  • Find out under safety stock.

For finished products store:

  • Receives finished product according to the delivery token of production area.
  • Preserves the packaged product report of QA department.
  • Prepares transfer note.
  • Prepares VAT challan.
  • Dispense FP according to FRFO basis.
  • Updates the current stock of finished goods.
  • Find out under safety stock.
  • Maintain the proper storage condition of finished product.

Room Condition/Critical Parameter:

Temperature:  

Around 250C (For finished products)

Around 20oC (For raw materials)

Relative humidity: 

Around 60% (For finished products)                               

Around 50% (For raw materials)                              

Machineries used in warehouse:

Forklift

Sugar Crushing Machine

Trolley

 

In plant training report Solid and Liquid Production Facility

Production

The production unit of XYZ Pharma Limited is highly maintained to minimize the risk of serious medical hazard due to cross-contamination, dedicated and self contained facilities are available for the production of Pharma products.

There are adequate working and in-process storage space to permit the orderly and logical positioning of the equipment’s and materials to minimize the risk of confusion between different pharmaceutical products and their components. To avoid cross-contamination and to minimize the risk of omission or wrong application of any of the manufacturing or control steps.

Pipe works, light fittings, ventilation points and other services are designed, and sited to avoid the creation of recesses that difficult to clean.

The area is effectively ventilated, with air control facilities appropriate to the products handled, to the operations undertaken and to the external environment. These areas are regularly monitored during both production and non-production period to ensure compliance with their design specification.

Premises for the packaging (Both primary and secondary) are specifically designed and laid out to avoid mix-ups or cross contamination.

Production equipment’s are thoroughly cleaned on schedule basis they are cleaned as back to back cleaning and complete cleaning.

Function of production

  • Commercial batch production
  • Readjustment of instruments and facilities according to the instruction of QA department
  • Small – scale experimental production of newly developed product according to the instruction of PD department.
  • Supervision of raw materials and packaging and final products in connection to QC department
  • Supervision of packaging process
  • Calibration and maintenance of the production unit’s machinery.

Objectives

  • Fulfill the market demand
  • High productivity
  • Reproducibility
  • Quality production

Units of Production Department

Compression

Coating

Dispensing

Granulation

Encapsulation

Room Available In Production Area

Blending Room

Change Room

Clean equipment Storeroom

Compression Room

Coating Room

Dispensing Room

Encapsulation Room

Granulation Room

IPQC Room

Liquid Dispensing Room

Milling Room

Office Room

Sieving Room

Washing Bay

Selection of Production Area

Solid dosage forms are some of the least expensive, most popular and convenient methods for drug delivery.

The Solid & Liquid Department of XYZ Pharma Ltd. consists of following units:

  • Tablet
  • Capsule
  • Powder for suspension
  • Syrup
  • Suspension
  • Bolus
  • Sachet          

Tablet

Tablets are the solid preparations each containing a single dose of one or more active ingredients and obtained by compressing uniform volume of particles.                    

According to British Pharmacopoeia, “Tablets are solid dosage forms circular in shape with either flat or convex faces and prepared by the compression or compaction of suitably prepared medicament by means the tablet machine”.

Tablets are intended for oral administration. Some are swallowed whole, some after being chewed; some are dissolved or dispersed in water before being administered and some are retained in the mouth where the active ingredient is liberated.

Essential qualities of good tablets:

  1. They should be accurate and uniform in weight.
  2. The drugs should be uniformly distributed throughout the tablet.
  3. The size and shape should be reasonable for easy administration.
  4. The tablet should not be too hard that they may not disintegrate in the stomach.
  5. They should be chemically and physically stable during storage.
  6. They should not break during transportation or crumble in the hand of the patient.
  7. There should not be any manufacturing defects like cracking, chipping or discoloration.
  8. After disintegration they should be readily dissolved.
  9. They should be easy and economical in production
  10. They should attractive in appearance

Types of Tablet According To BP

  • Conventional/Uncoated tablet
  • Coated tablet
  • Effervescent tablet
  • Soluble tablet
  • Gastro-resistant tablet
  • Modified-release tablet
  • Tablet for using in the mouth
Ingredients of tablet

Methods of tablet preparation:

  • Wet granulation
  • Dry granulation
  • Direct compression

Granulation:

Granulation is the process in which primary powder particles are made to adhere to form larger multi-particulate entities called granules. Pharmaceutical granules typically have a size range between 0.2 and 4.0 mm depending on their subsequent use.

Reasons for granulation:

  • To improve the flow properties of the powder mix.
  • To improve the compaction characteristics of the powder mix by adding a solution binder.
  • To improve mixing homogeneity.
  • To decrease dusting.
  • To increase the bulk density of the powder mix & thus ensure that the required volume of can be filled in to the die.

Classification of Granulation

Two types of granulation process are performed in this unit

in plant training report, type of granulation

Wet Granulation

In this method water media is used for granulation. This is the most XYZ way to form tablet granules. The steps of tablet wet granulation are:

in plant training report

DRY GRANULATION

This method is used for powders, which require granulation and sensitive to moisture and water.

in plant training report

Critical parameters of granulation

1. In CMG-

  • Mixing time &
  • Agitator & side cutter starting

2. In FBD-

  • Inlet temperature
  • Exhaust temperature
  • LOD

Blending

Blending is the process of mixing lubricants, glidants and colorants with the granules prior to compression (in case of granules containing the active Ingredients) or mixing of active ingredient/s along with lubricants, glidants and colorant with the placebo granules (in case of granules without the moisture sensitive active ingredients) prior to compression. So, the process is often-called lubrication or remixing.

Blending procedure

For granules containing active ingredient/s the following procedure is used in the blending units of XYZ Pharmaceutical Limited;

  • Remove the blender cleaned label & update the logbook with product detail.
  • Display a product identification label at the display board.
  • Verify that the instruments to be used are within their calibration period Matcon IBC blender process timer. Blend Speed Indicator.
  • Check that the lid is securely fitted to the IBC.
  • Blend the IBC for 20 minutes at 15 rpm
  • Include the blender printout in the batch wallet.
  • Verify that the balances used for the IBC weighing are within their calibration period.
  • Weigh the IBC to determine the granules yield.
  • The weight of granules should be between 309.054 kg to 312.176 kg (99-100%).
  • Notify Executive if the yield is outside the limits. Executive to investigate and provide a reason.  

BLENDING CRITICAL PARAMETERS:

  • Blending time
  • RPM (Rotation Per Minute)

Sieving

The sizing (size reduction, milling, crushing, grinding, pulverization) is an impotent step (unit operation) involved in the tablet manufacturing.

In manufacturing of compressed tablet, the mixing or blending of several solid ingredients of Pharma is easier and more uniform if the ingredients are approximately of same size. This provides a reater uniformity of dose. A fine particle size is essential in case of lubricant mixing with granules for its proper function. 

Sieving process

  • Record temperature and relative humidity of the area before sieving.
  • Remove the equipment-Cleaned label. Update the log book with product details and display a product identification label at the room entrance.
  • Check that the raw materials are correctly labeled and sealed and have been weighted.
  • Transfer the following raw material into 1000 L IBC
  • Sieve the following raw materials through the Russell Finex Sieve fitted with 630 μm pore size screen into a labeled polybags.

COMPRESSION

After granulation, the granules are compressed to form tablets of definite Shape, size, hardness, weight & thickness. Compression unit of solid Department of XYZ Pharma has 2 compression machines. 

Compression can be defined as the technique of applying force or pressure to the granules or powders (in case of direct compression) to produce tablets of desired shape and size with the help of tablet press machine.  

Two types of compressions are seen in the tablet press units of the factory; they are-

  1. Compression of previously made granules
  2. Direct Compression

Direct Compression This is another method of tablet manufacturing. The materials are directly compressed to form tablets. The steps of direct compression are:

In plant training report

Processing problems in tablets:

Capping and Lamination:

Capping is term used to describe the partial or complete separation of the top or bottom crowns of the tablet.

Lamination is the separation of a tablet into two or more distinct layers.

These problems can be overcome by:

  1. Reducing the percentage of fine in the granulation.
  2. Maintaining desired moisture level in the granulation.
  3. Adjusting the speed and compression force.
  4. Replacement of defective punches and dies.

Picking and Sticking:

The term picking signifies the removal of material from the surface of the tablet and its adherence to the punch face.

Sticking refers to the adherence of tablet material to the die wall. This result in difficulty in the ejection of tablet which may causes further chipping of tablet edges.

These problems can be overcome by:

  1. Proper designing of punches.
  2. Chrome plating punch surface. 
  3. Adequate drying of granules.
  4. Using antiadherent like talc, magnesium stearate and colloidal silica.

Mottling:

It refers to the unequal distribution of color on the surface of tablet. It is due to difference in the color of drug and excipients, improper distribution of colorants or migration of dye to the surface of granulation during drying.

This problem can be overcome by:

  1. Using a dye that can mask of all ingredients.
  2. Using the alternate solvent system for the granulation.
  3. Reducing the drying temperature of the granules.
  4. Using dyes and lakes of very fine particle size.

Weight variation:

This problem is encountered when the tablets do not have a uniform weight. This problem is associated with poor flow of the granules, segregation of the different of the granulation or incorrect lubrication of granulation.

This problem can be overcome by:

  1. Using granules of uniform particle size distribution.
  2. Decreasing the fine.
  3. Using proper concentration of lubricants, glidants etc.

Hardness variation:

This problem is encountered when the tablets vary significantly in their hardness. Hardness depends on the weight of the materials being compressed and the space between the upper and lower punches during the compression. If the weight of the materials or the distance between the punches varies, the hardness will also vary.

Double impression:

This problem is generally evident in cases where the lower punches have a monogram or other engravings on them. On some machines, the lower punch is free to drop and travel for a short distance before ascending to eject the tablet out of the die. During the free travel period, the punch may rotate and make a new lighter impression on the bottom of the tablet. This problem can be overcome by controlling the undesirable movement of the punches.

Tablet Coating

Tablet coating can be defined as the extra layer of the outer surface of the tablet, which mask the unwanted taste of the tablet and makes it palatable to the patient.

Tablet coating is the application of a coating material to the exterior of a tablet with the intension of conferring benefits and properties to the dosage form over the uncoated variety. 

Function of Coating

Integrate another drug or formula adjuvant in the coating to escape chemical incompatibilities.

Cover the taste, odor or color of the drug.

Deliver physical and chemical protection of the drug.

Regulate the release of drug from the tablet.

Provide safeguard to the drug from the gastric environment of the stomach with an acid resistant enteric coating.

Recover the pharmaceutical elegances by use of special colors and contrasting printing.

Main types of tablet coating:

Sugar coating

Film coating

Sugar coating:

A compressed tablet may be coated with suitable color and/unicolor sugar. This coating layer is very much water-soluble and readily dissolve after swallowing. 

Sugar coating process involves four separate operations:

Sealing

Sub coating

smoothing

Polishing and finishing

Film coating:

This is the most popular coating form nowadays. More than 95% coating demonstrate film coating except enteric coating.

Following materials used for film coating:

Film formers:

These are mainly polymers and the base of a coating formula. These can be-

Non enteric:

Methylhydroxy Ethylcellulose, Hydroxypropyl Methylcellulose, Ethyl cellulose, Na-CMC Povidone (PVP)-30 etc.

Enteric:

Hydroxypropyl Methylcellulose Phthalate, Polyvinyl acetate Cellulose acetate Phthalate, Phthalate etc.

Solvents:

Ethanol, Isopropanol, Methanol, Methylene chloride etc.

Plasticizers:

Glycerin, Propylene glycol, Polyethylene glycol etc.

Opaquant-extenders:

Aluminium silicate, Magnesium oxide, Titanium dioxide, etc.

Colorants:

FD&C and D&C colorants.

Miscellaneous coating solution components:

Flavors, Sweeteners, Preservatives etc.

Defects of coated tablet

Cracking

Core erosion

Edge chipping/erosion                                               

Logo bridging

Logo in filling

Picking/sticking Tablet to tablet color variation

Critical parameters of coating

  • Atomization pressure
  • Steam pressure
  • Spray pattern
  • Gun to bed distance
  • Spray rate
  • Pan depression
  • Program parameter
  • Height of core sample after pre-jag drying cycle.

In plant training report of In-Process Quality Control:

During the compression of tablets, in-process tests are routinely run to monitor the process, including tests for-

  • Appearance
  • Thickness
  • Hardness
  • Friability
  • Weight variation
  • Disintegration
  • Dissolution
  • Moisture content

Capsule preparation

The word capsule is consequent from the Latin word capsules denote a small box. In Pharmacy, the term Capsule is use to define an edible package made from gelatin, which is filled with medicines to produce a unit dose mainly for oral use.

As per U.S.P. ‘Capsules are solid dosage forms in which the drug is enclosed in either a hard or soft soluble container or shell of a suitable form of gelatin.’

As per B.P., ‘Capsules are solid preparation contain hard or soft shells of various shapes and capacities, usually comprising a single dose of active ingredient.’

So the complete definition is, ‘Capsule may be well-defined as solid dosage forms with the shells of hard or soft gelatin or any other suitable material, if various shapes & capacities, containing a single dose of active ingredient. They are suggested for oral administration.

The active is filled in the empty the hard gelatin capsule shell in the form of

Powder

Pellets

There are 8 different sizes of empty hard gelatin capsule shells are available –

Capsule shell size 000

Capsule shell size 00

Capsule shell size 0

Capsule shell size 1

Capsule shell size 2

             

Encapsulation Process by Automatic Capsule Filling Machine:

For encapsulation of pellets the following procedure is done with the help of Automatic Capsule Filling Machinein the capsule filling units of XYZ Pharma Ltd.

Encapsulation

Capsules are solid dosage form in which the drug substance is enclosed in either a hard / soft gelatin soluble container or shell of a suitable form of gelatin.

Capsule encapsulation flow:

There are two types capsule filling:

  1. Pellet filling process
  2. Powder filling process
In plant training report

Encapsulation process by manual capsule filling machine:

For encapsulation of powder the following procedure is done with the help of Manual Capsule Filling Machinery hand in the capsule filling units of the industry.

In plant training report

Packaging

Packaging protects the products for sale, storage, distribution and use. Packaging denote evaluation, design and production of different packages. It is the convenient system for warehousing, transport, sale, logistics and consumer level use.

Packaging and package labeling have numerous purposes:

  • Accessibility
  • Barrier protection
  • Containment or agglomeration
  • Information transmission
  • Marketing
  • Physical protection
  • Safe keeping

Packaging types:

Primary packaging:

The single unit of the package which generally direct contact with the products and protect the products from surrounding environment in undesirable conditions.

Secondary packaging:

This is the outer layer of primary packaging which supports the primary packaging and makes the product elegance outfit to the end user.

Tertiary or Master packaging:

This type of packaging mainly help during transporting of various types of light weight or heavy weight products. Also help to storage of the products for a longer period of time.

Blistering materials:

It is three types:

  • ALU-ALU types
  • ALU-PVC type
  • ALU-PVDC type

Room condition/Critical parameter:

Temperature:  

Below 250 C

Relative humidity:  

Below 60%(Manufacturing Area)                      

Below 50%(Packaging Area)

Pressure:  Positive pressure in corridor and negative pressure in room and pressure difference [12~15] Pa

In plant training report

IPC For packaging:

  • Leak test
  • Coding
  • Appearance
  • Stoppages/Adjustments

BMR, BPR & its activity & regulations:

BMR includes the following records:

  • Batch no.
  • Batch size
  • Batch Quantity
  • Date of requisition
  • Date of commenced
  • Date of completion
  • Change over checklist
  • Manufacturing procedure
  • Name of product
  • It must be checked by QA officer
  • Product name
  • Product line clearance

BPR means Batch Packaging Record. In this documentation the following guideline is given about packaging of a batch product:

BPR contains following records:

  • Batch No.
  • Batch size
  • Batch Quantity
  • Bulk product received
  • Carton over printing record
  • Change over checklist for packaging line
  • Date of requisition
  • Date of commenced
  • Date of completion
  • Name of packaging materials
  • Over printing inspection
  • Product name
  • Product order number
  • Packaging line clearance
  • Printing line clearance
  • Specification
  • It must be checked by QA officer

Packaging Line Clearance:

It denote clearance of every packaging materials of previous batch of same or different product before packaging started.

  • Previous product must be removed
  • Previous packaging materials must be removed
  • Check by QA officer

Machine operation & cleaning:

  • Most of the machines are PLC (Programmable Logic Control) controlled.
  • Some machines are manually controlled.
  • Operated by skilled operator.
  • Some machines have CIP (Clean in process) system such as coating machine.
  • Some movable parts such as dies, punches and disc are discharged to clean in cleaning room.

Following materials are used for the cleaning

  • Compressed air for plastic bottle
  • Sodium bicarbonate for coating machine
  • Sodium lauryl sulphate 4% (SLS) for all machine
  • 70% IPA (Iso-propyl alcohol)
  • Tape water

Prevention & Maintenance system:

  • Cleaning room with every production floor.
  • Epoxy paint in the production floor facilitate easy clean & dust free.
  • Gown, musk, hand gloves are used to prevent contamination.
  • HVAC system maintains “Clean Corridor Concept” (Corridor with positive pressure).
  • Regular training for operators.
  • Sandwich wall (45 mm diameter) maintains pressure; prevent passage of air, dust, no sedimentation & ease to clean.
  • SOP for all important activities.
  • Skilled operators.

Shop floor planning:

The overall arrangement of production floor during production which involve-

  • Manpower scheduling
  • Machine scheduling
  • Packing material scheduling
  • Product scheduling

And this planning occurs by the three phase in a month. This is very much useful for the appropriate utilization of existing resource. And it also prevent system lose in the production area.

Machineries used in solid & liquid area:

  • Bin Lifting Device
  • Blister Machine
  • Bottle Washing Machine
  • Cap Sealing Machine
  • Cosmic Bin Blender
  • Cream Manufacturing Vessel
  • Cream Transfer Vessel
  • Encapsulation Machine
  • Fluid Bed Equipment
  • Fluid Bed Dryer
  • Film Coating Machine
  • Homogenizer
  • Liquid Filling Machine
  • Manufacturing Vessel
  • Sartorius
  • Steam Jacket Vessel
  • Storage Vessel
  • Sugar Coating Machine
  • Super Mixer Granulator
  • Tablet Compression Machine
  • Transfer Vessel
  • Tube Filling Machine

Machineries used in In Process Control:

  • Disintegration Tester
  • Friability Tester
  • Hardness Tester
  • Moisture Analyzer
  • Tapped Density Tester
  • Weighing Balance
In plant training report

In plant training report Cephalosporin

Now a days, Cephalosporins are most prescribed drugs of antibiotics especially in Cefixime Trihydrate and Ceftriaxone sodium. The Cephalosporins are very commonly structurally similar to Penicillin and having beta-lactam ring structure which interfere the synthesis of bacterial cell wall hence work as bactericidal.

Cephalosporins are indicated for the treatment of infections and prophylaxis and treatment of infections caused by susceptible bacteria. The 1st generation cephalosporins are active against Gram-positive bacteria and succeeding generations have increased activity against Gram-negative and Gram-positive bacteria.

Cephalosporin’s can be divided into five generations:

1st   generation cephalosporins:

Cefadroxil

Cephalexin

Cephaloridine

Cephalothin

Cephapirin

Cefazolin

Cephradine

2nd  generation cephalosporins:

Cefaclor

Cefoxitin

Cefprozil

Cefuroxime

3rd  generation cephalosporins:

Cefdinir

Cefixime

Cefpodoxime

Ceftibuten

Ceftriaxone

Cefotaxime

4th  generation cephalosporins:

Cefepime

Cefluprenam

Cefozopran

Cefpirome

Cefquinome

5th  generation cephalosporins:

Ceftobiprole

Ceftaroline

In plant training report

Room condition/Critical parameter:

Temperature:  

Below 250 C.

Relative humidity:  

Below 60% (Manufacturing area)                          

Below 50% (Packaging area)

Pressure:

Positive pressure in corridor and negative pressure in room and pressure difference 12~15 Pa.

Machineries used in cephalosporin area:

  • Blister machine
  • Bottle washing machine
  • Dry mixing
  • Leak tester
  • Encapsulation machine
  • Film coating machine
  • Macofar micro 9 line Filling & Sealing Machine
  • Tablet compression
  • Powder loader
  • Powder for suspension machine
  • Sealing & labeling machine
In plant training report

Condition for different portion is given bellow:

Tablet

Humidity: Bellow 50%

Temperature: Bellow 25°C

Capsule

Humidity: Bellow 50%

Temperature: Bellow 25°C

Dry syrup

Humidity: Bellow 45%

Temperature: Bellow 25°C

Vial

Humidity: Bellow 40%

Temperature: Bellow 25°C

In plant training report

In plant training report of Sterile Department

The whole area of sterile section of The XYZ pharmaceuticals Ltd is covered with HEPA filter and laminar airflow. There are air lock systems with air shower and pass boxes to pass the raw materials, ampoules, vials, finished products and other sterile substances to the filling and sealing area.

They take all protective measure of aseptic techniques to prevent particulate and microbial contamination.In The XYZ  pharmaceuticals Ltd. has two divisions of sterile section, one is injectable product division and another is ophthalmic product division

In plant training report of INJECTABLE DIVISION

Injectables are sterile and pyrogens free products that planned to be administered in the body with the help syringe and needles through various routes such as intravenous (IV), intrathecal (IT),  intramuscular (IM), intraperitoneal (IP) etc. The XYZ pharmaceuticals Ltd. produces Injectables in vials and ampoules meant for administration in the body through IV or IM routes.

As the products straight go to circulation, they must be free from any microbial contamination, toxic components and should have and remarkably high level of purity. So, The XYZ pharmaceuticals Ltd. has distinct section for injectables, which comprise of several sub units.

In The XYZ pharmaceuticals Ltd. produce three types of injectable products, they are-

  • Aseptic products
  • Terminally sterilized products
  • Powder for injection

Sterilization:

Sterilization is the progression of killing or removing bacteria and all forms of living microorganisms and their spores from preparations.

Methods of sterilization:

Moist heat sterilization:

It is used to sterilize ampoules, glass bottles, vials, rubber closures and different parts of equipment.

It is also cast-off to sterilize dressings, gowns etc.

Dry heat sterilization:

It is used to sterilize glass bottles, ampoules vials, and closures.

It is also used to sterilize different parts of equipment.

Radiation sterilization:

By using gamma radiation a great number of pharmaceuticals including minerals, vitamins, antibiotics and peptides are sterilized. It is mainly used for the sterilization of surgical gowns, plastic containers, syringes, petridishes, hood and mask etc.

Ultraviolet light is usually used for the reduction of air born contamination in the aseptic room and the area of working surface.

Gaseous sterilization:

Ethylene oxide is cast-off in the terminal sterilization of medical device including tubing, dressing, intravenous infusion sets, syringe and needles etc.

Formaldehyde is mostly used for the fumigation of empty air flow cabinets and rooms to eliminate microbial contamination from solid surface.

Filtration sterilization:

It is perfect for the sterilization of thermolabile substances.

For both sterilization and amplification.

The method is beneficial for sterilization of great quantities of solutions.

Lyophilization:

Lyophilization (well known as Freeze-drying) is a dehydration procedure characteristically used to preserve a fresh material or make the material more suitable for transport. Freeze-drying works by freezing the material and then dipping the surrounding pressure to permit the frozen water in the material to sublime straight from the solid phase to the gas phase.

Environment monitoring:

Environmental monitoring is one of the most important tasks in the sterile department. It is a regular check of view to take timely corrective measures for maintaining a favorable manufacturing environment.

In plant training report

Gowning System:

In the manufacture of sterile drugs Gowning System is most important.

The gown must be sterilized and made of material, which will not shed particles.

Everyone entering a clean or a sterile area must change gear garments and wear special garments, which includes head, musk and footwear.

The number of people must be as low as possible and restricted to authorized people.

Room condition/Critical parameter:

Filling containers under aseptic conditions is the most critical step in the production cycle.  The most effective ones are claimed to retain 99.997% of the particles. Laminar Air flow cabinet is used under HEPA filters and air velocity is 0.45 ms-1. Filling area is class-A zone whereas the background is class-B zone.

Temperature:   

Below 250 C.

Relative humidity:  

Below 60% (For liquid vial).                           

Below 35% (For powder for suspension).

Pressure: 

Negative pressure in corridor and Positive pressure in room and pressure difference 12-15 Pa.

Aseptic Room Preparation:

The purpose of the aseptic technique is to prevent microorganisms from the environment.

To design of an aseptic room the following factors must be borne in mind:

Site

Size

Windows

Doors

Surfacing materials

Services

Corridors

The aseptic procedure comprises the following steps:

Sterilization of equipment’s

Sterilization of containers

Sterilization of gown.

Filling of the solution in the containers under aseptic conditions

Double door air lock system.

Pass box for materials.

Filling containers under aseptic conditions is the most critical step in the production cycle. This technique is filtration sterilization. HEPA (High Efficiency Particulate Air) filter is used. The most effective ones are claimed to retain 99.997% of the particles. Laminar Air flow cabinet is used under HEPA filter. Filling area is class-A zone whereas the background is class-B zone. The processing rooms must be supplied and flushed with air under controlled positive pressure.

Machineries used in SVP & ophthalmic area:

Weighing Balance

Manufacturing Vessel

FD Manufacturing Vessel

Autoclave

Eye drop Filling, Sealing &

Plugging Machine

PH Meter

Integrity Test Machine

Capping Machine

Ampoule Leveling Machine

Insulin:

This act as hormone central regulate carbohydrate and metabolism in the body. Insulin relating cell as muscle, liver and fat tissue take glucose from the blood and store it to the muscle and liver as glycogen form.

Insulin inhibit the release of glucagon by stopping the use of fat as an energy source. When body face metabolic syndrome and metabolic disorder diabetes mellitus release excess amount of glucose from the blood that is harmful for body tends to toxic condition.

Room condition/Critical parameter:

Temperature:   Below 250 C.

Relative humidity:   Below 60% (Manufacturing area).

Pressure:  Positive pressure in corridor and negative pressure in room and pressure difference 12-15 Pa.

Machineries used in insulin area:

Chutian Vial Filling & Plugging Machine

Dryer

Electrolab Vial Filling Machine

Insulin Cartage Filling & Stoppering Machine

Insulin Cartage Washing Machine

Manufacturing Vessel

Prefilled Syringe Machine

Rotary Vial Washing Machine

Rotary Ampoule Filling Machine

Dialysis

The dialysis process remove the excess water from the blood and this process primarily use in the people who are facing kidney impairment. This process also use in the people with severe kidney dysfunction.

There are two primary types of dialysis:

Hemodialysis:

Generally, the Hemodialysis process remove water and wastes by circulating the blood outside body via an external filter. This system is known as dialyzer contains a semipermeable membrane.

Peritoneal dialysis:

In peritoneal dialysis process, remove water and wastes by circulating the blood inside body by using peritoneal membrane. The peritoneum is a natural semipermeable membrane.

There are three type of Dialate preparation in XYZ pharmaceuticals ltd.

Dialysis Solution A:      Acidic product, pH(1.8-2.8)

Dialysis Solution B:      Basic product, pH (7-9)

Dialysis Solution AC:   Acetate product, pH(7.2-7.4)

Room condition/Critical parameter:

Temperature: Below 250C               

Relative humidity: Below 60%

Machineries used in dialysis area:

Manufacturing Vessel

Transfer Pumper

Pressure Vessel

Filling Machine

In plant training report Infusion Unit

As the infusion introduced to the systemic circulation of the patient so highest quality and purity strictly maintained in every steps of the manufacturing process.In XYZ Pharmaceuticals the quality & purity of infusions products are maintained strictly. They mainly produce dextrose saline.

The infusion preparation involves Two main operations-

  • Preparation of WFI
  • Preparation of solution

The whole area of sterile section of The XYZ pharmaceuticals Ltd is covered with HEPA filter and laminar airflow. There are air lock systems with air shower and pass boxes to pass the raw materials, ampoules, vials, finished products and other sterile substances to the filling and sealing area. They take all protective measure of aseptic techniques to prevent particulate and microbial contamination.

In The XYZ pharmaceuticals Ltd. has two divisions of sterile section, one is injectable product division and another is ophthalmic product division.

Injectables are sterile and pyrogens free products that intended to be administered in the body with the help syringe and needles through various routes such as intravenous (IV), intramuscular (IM), intrathecal (IT), intraperitoneal (IP) etc.

The XYZ pharmaceuticals Ltd. produces Injectables in vials and ampoules meant for administration in the body through IV or IM routes. As the products directly go to circulation, they must be free from any microbial contamination, toxic components and should possess and exceptionally high level of purity. So, The XYZ pharmaceuticals Ltd. has separate section for injectables, which consist of several sub units.

In The XYZ pharmaceuticals Ltd. produce three types of injectable products, they are-

  • Aseptic products
  • Terminally sterilized products
  • Powder for injection
process flow diagram of LVP

LVP stands for large volume parenteral liquid. XYZ Pharmaceuticals Ltd. produces a variety of infusion products

Cholera saline

Ciprofloxacin 0.2% w/v

Dextrose 5% w/v

Dextrose 10% w/v

Dextrose 5%w/v and Sodium Chloride 0.9% w/v

Hartmann’s solution

Levofloxacin 0.5% w/v

Metronidazole 0.5% w/v

Sodium Chloride 0.9% w/v

Amino Acid

The amino acids consider the building block of the proteins and act as intermediates in metabolism. There are almost twenty amino acids found in the protein convey the wide range of chemical variety. The amino acids are consider the critical to the life as its form protein in the body and have the central role in the biochemistry.

The amino acids are also use in food technology, food supplement, nutritional supplements and fertilizer. Fatty emulsion Normal saline [0.9% Sodium Chloride], Dextrose solution and is used to provide nutritional supplements.

Room condition/Critical parameter:

Temperature:  

Below 250 C.

Relative humidity:  

Below 60% (Manufacturing area).                              

Below 50% (Packaging area).

Pressure: 

Positive pressure in corridor and negative pressure in room and pressure difference 12-15 Pa.

Machineries used in LVP & amino acid area:

Automatic Filling & Sealing Machine

Cartage Filter

Desktop Filling Machine

Filter Integrity Tester

Homogenizer

Manufacturing Vessel

Sealing Machine

Superheated Water Spray Autoclave

Cleaning and Maintenance:

The manufacturing vessel is fitted with a mobile auto cleaning in place (CIP) and sterilization in place (SIP) unit from Pharmalab. CIP is done with (80-90)°C WFI.  When filling starts the first 8 to 10 bags are rejected to make sure the cleaning WFI is fully expelled from the system.

In plant training report Quality Assurance

Quality Assurance refers to a program for the systematic monitoring and evaluation of the various aspects of a project, service, or facility to ensure that standards of quality are being met.

Quality Assurance Activities

Change Control Request

Customer complain handling

Corrective action, preventive action (CAPA)

Internal audit i.e. self-inspection

In process Quality Control[IPQC]

Out of specification

Quality incident report

Regulatory activities

Training of GMP and SOP

Vendor Audit

Validation

List of documents for audit:

Annual product review

Cleaning validation

Customer Complaint

Change control Management

Documents and trend analysis of water system

Documents and trend analysis of environment monitoring

Deviation Handling

Hold time study documents

Internal quality audit/Self Inspection

Out of specification

Product recall

Process validation documents

Qualification documents of water system

Qualification documents of HVAC system

Qualification documents of relevant process machine

Quality manual

Quality incident report

Real time stability

Site master file

Safety, Health & Environment policy

SOP list & SOP files

TSE/BSE related document

Training related document

Validation master file

Vendor audit schedule

Vendor list

Validation

Its establish the documentary evidence where a process, procedure and activity carried out and in production stage, it can be maintain compliance in all stages.

Cleaning Validation

Process Validation

Analytical Method Validation

Computer System Validation

Qualification includes the following steps:

Design Qualification (DQ):

Demonstrate the operational and functional specification of a program, instrument or equipment and every single details that specified the supplier as per URS [User Requirements Specification].

Installation Qualification (IQ):

Demonstrate that the equipment or a specific process meets the specifications, installed properly and all documents, components present to continue the Installation process.

Operational Qualification (OQ):

Demonstrates that the specific installed equipment’s or process operate correctly without any significant error.

Performance Qualification (PQ):

Demonstrates that the specific installed equipment’s or process operate correctly over a period and continue the process smoothly.

In-Process Quality Control

In-process Quality Control depends on the following parameters:

For tablet

Appearance

Average weight

Blend uniformity

Disintegration

Dosages uniformity

Friability

Hardness

Loss on drying (LOD)

Thickness

Variation

Weight

For Capsule

Appearance

Average weight

Close length

Disintegration Time

Empty Capsule shell weight

Locking

Uniformity of weight

For Liquid

Appearance

Assay

Odor

pH

Viscosity

Weight per ml

In plant training report of Quality Control Department

The activities of the Quality control is the part of the pharmaceutical company to run the smooth operation. Drug must be tested through QC department before any type of marketing activities. A better medicinal formulation must be develop and their testing method must be validated for the evaluation of the testing method.

The head of the quality control generally has the following responsibilities:

Analyst Validation

Approve or reject of raw materials

Approve packaging materials

Approve sampling and sampling procedure

Evaluate batch records

Ensure necessary testing activities

Release intermediate, bulk and finished

Routine calibration of the equipment’s

Quality control areas:

QC Laboratory must be dedicated from the production facility of the respective industry. A well equipped laboratory must be available before starting commercial production. Adequate space must be ensure for reference stands, sample, solvents, reagents, machine etc.

Good Laboratory Practice:

GLP principles include:

Equipment’s, reagents and materials

Facilities

Performance of study

Organization and personnel

Quality assurance program

Reporting of results

Standard operating procedures

Storage of records and reports

Test systems

Test & Reference items

Sampling:

This is to be perform by QC department to ensure that the raw materials, packaging materials and any other parameters just sampled and tested properly. For the Active Pharmaceutical Ingredients [API], the sample withdrawn from each container. For the excipients, sampling is performed by the formula: √n+2, where n is the number of container.

In XYZ Pharma Ltd, Quality Control department composed of two departments. There are-

Analytical lab

Microbiological lab

Analytical lab

Products are tested in three steps:

Raw material quality control

In process quality control

Finished product quality control

Raw material quality control:

Materials must be tested as they are used in parenteral preparations and any other preparation. It must be ensure that all physiochemical parameters meets its desired specifications.

The following tests are performed:

Assay of the drug

Density of powder

Flow properties of powder

Glass test on container

Identify test on rubber closure

Particles count in vehicle

Pyrogen test for WFI

Quality Control Parameter

Raw materials specification depends upon the following parameters:

Appearance

Absorptivity

Assay (HPLC)

Bulk density

Odor

Identification

Loss on drying

Heavy metals

Melting point

pH

Residue on ignition

Specific gravity

Solubility

Sterility/Pyrogen Test

Viscosity

Turbidity

Water content


FINISHED PRODUCT

Finished product specification depends on the following parameters

FOR TABLET

Dosage uniformity

Loss on drying (LOD)

Disintegration

Dissolution

Average weight

Hardness

Friability

FOR CAPSULE

Average weight

Assay

Dosage uniformity

Disintegration Time

Dissolution

Loss on drying (LOD)

FOR LIQUID

Appearance  

Assay

Odor

pH

Viscosity

Weight per ml

PACKAGING MATERIALS

Check parameters of packaging materials

Aluminum foil

%of aluminium

Thickness

Width

Cartons

Breath

Color

Code No.

Dosage

DAR No.

GSM

Length

MRP

Text

Type of paper

Catch covers

Same test as done for cartons Contains no MRP.

Labels

Breadth

Chromolex papers

GSM

Length

Type of paper used:

Inserts

Breadth

Length

Offset paper are used for inserts

Text

Type of paper used:

Corrugated board/Master carton/Shipper

Type: 3 Ply or 5 Ply

Liner should be of definite grammage

Master gum should be used

Text

Machineries used in quality control department:

[Analytical Section]

Atomic Absorption Spectrometer

Centrifuge Machine

Dissolution Tester

Drying Oven

Furness Atomizer

FTIR

Flame Photometer

Fume Cupboard

HPLC

Karl Fischer Titrate

Liquid Particle Counting Machine

Muffle Furnace

Polarimeter

pH  Meter

Refrigerator

Shaking Water Bath

Shaker

Tap Density Tester

UV Spectrophotometer

Ultrasonic Bath

In plant training report of MICROBIOLOGICAL LAB

The role of Microbiology section in Quality Control Department at XYZ Pharmaceuticals Ltd. is increasing daily to include a wide variety of quality and safety issue.

Microbiology section is one of the vital sections of any pharmaceuticals to confirm quality product. The Microbiology section of Quality Control Department in XYZ Pharmaceuticals Ltd. is well decorated and separated that assesses microbial load and particulate matter of raw material as well as finished product mainly sterile product. 

Activities performed by Microbiology section are:

Floor/Environment Monitoring:

Air Particle Count

Personnel Hygiene

Settle Plate Count

Swab Test

Microbiology Lab Work:

Bioburden Test

BET/LAL Test

Microbial Assay

Microbial Limit Test

Sterility Test

Water Treatment

Following techniques generally employed for monitoring:

Airborne particle count (non-microbiological):

This is done by using particle counter.

Settle plate technique:

The Petridishes are exposed in production area contains microbiological growth media in agar incubated for 5 days at 30°C.

Surface swabs technique:

The Sterilized swabs of cotton buds readily moistened in a liquid culture media then the specific area of a surface then swabbed and sampled from that surface and incubated. Mainly applied in solid surface, personnel, equipment, garments etc.

Air sampling:

Done for microbial growth in air.

LABORATORY TEST:

Sterility test:

It is done for raw materials and product materials. 14 days are require to perform  sterility test.

Two types:

Direct method. Filtration method (mostly used).

Limit test/Contamination test:

This test is done for checking raw materials. Three types:

Filtration.

Pour plate

Spread plate.

Endotoxin test/LAL test:

The in-vitro test for determination of pyrogen with help of the lysate of amoebocytes of limulus polyphemus.

Machineries used in quality control department:

[Microbiology Section]

Analytical Balance

Compound Microscope

Centrifuge

Cooled Incubator

Dry Heat Sterilizer

Flocculation Water Bath

Incubator

Laminar Air Flow

Top Loading Autoclave

Water Bath

In plant training report of Product Development

The product development department of the pharmaceutical company play a vital role in the in terms of the development of the cost effective drugs and support the same throughout their life cycle.

This involves:

Pharmaceutical formulation:

Proceed to develop molecules into a specific dosage format as Tablet, Capsule, and Injectable etc.

Process development:

After development a successful formulation, a specific, precise, smooth process to be develop to reproduced the same in commercial scale.

Pharmaceutical analysis:

An analytical method to be develop to analysis the physiochemical properties of the molecule including physical properties, chemical structure, stability and presence of various impurities.

Pharmaceutical maintenance:

Changes or improvements require in the commercial scale i.e. analytical methods, manufacturing processes and formulation as when required.

The section also performs the following duties:

Develop specifications for all starting materials, excipients and finished products

Develop proper batch documentation system

Develop the old and new products

Identity problems and takes positive action

Validates the product formulation

XYZ Pharma Ltd. has a very well equipped and separate product development facility to carryout formulation development work and to conduct storage stability studies following ICH guidelines which is also the one of its kind in USA.Product development department prepares the manufacturing instruction, coating instruction (if necessary), packaging instruction, product specification and testing procedure file of the new product. PD develops the formulation on the basis of trial and error method.

Consists of two parts:

Formulation 

Analytical

Stability Study:

There are two methods by which stability is tested:

Real-time stability study

Accelerated stability study

PD department work flow

Machineries used in product development department:

ANALYTICAL SECTION

Disintegration Tester

Dissolution Tester

Drying Oven

Friability Tester

Fume Cup Board

Hardness Tester

HPLC

Hot Plate Stirrer

Karl Fischer Titrate

Moisture Analyzer

pH Meter

Shaker

Ultrasonic bath

Water Purifier

Water Bath

FORMULATION SECTION

Digital High speed Mixer

Double Cone Blender

Film & Sugar Coating Machine

Fluid Bed Dryer

High Speed Mixer

Oscillating Granulator

Tablet Compression

In plant training report of ENGINEERING

Engineering Department of XYZ Pharma Ltd. plays a major role in maintaining all other departments & supplies energy to these departments.

The major utilities that serve the Engineering department are as follows:

Air compressor

Building Management System

Boiler plant

CSB (Central Service Building)

ETP (Effluent Treatment Plant)

Generator

HVAC system

Pump house

Purified water plant

Soft water plant

Pre-treatment plant

In plant training report of Power Plant:

The power plant is the major area of a pharmaceutical company. Different type of power plant use in pharma company which convert energy into electrical energy.

HVAC:

HVAC [Heating, Ventilation, and Air Conditioning] can be defined as automotive environment controlling system. This system, mainly designed based on mechanical engineering where heat transfer, fluid mechanics and thermodynamics play vital role.

This system is mainly design for medium to high industry environment and provide comfort level of Temperature and Humidity and Fresh Air the major.

Purified water plant

Effluent Treatment Plant:

The tenacity of an Effluent Treatment Plant (ETP) is to reduce Biological Oxygen Demand (BOD) & Chemical Oxygen Demand (COD) of pharmaceutical idle chemicals, powders and waste materials which may cause severe destructive effect on environment as well as human health.

Effluent management in XYZ Pharma Ltd. is carried out through bio-spiral technology as aerobic treatment process. The capability of the plant is 30 m3/day. The quality of output is dischargeable into the public sewer or re-useable for gardening & land scarping.

ETP

Machineries used in engineering department:

Boiler

Diesel Power Generation

Gas Power Generation

In plant training report of Administration

XYZ Factory Administration Department is a supporting department that smoothing manufacturing activities.

The overall tasks of the factory administration are as follows:

Housekeeping:

Keeping the whole administration unit as well as the premise clean and attractive looking.

Canteen management:

The company has a yearly contact with a caterer who supplies meals as well as snacks. The raw food that is brought in every day is checked by supervisors to ensure desired quality.

Safety and security:

The Company has its own security personnel. For safety there are fire extinguishers and water hoses at specific location as well as emergency exits for safe evacuation.

Vehicle management:

The vehicles work on a fixed pickup and drop schedule. They are routinely maintained at fixed workshops.

Protocol:

The administration looks over the visas, accommodation and transportation of international bodies that want to visit the plant.

Waste management:

Thus, waste management is carried out to ensure that the wastes are properly separated, recycled and disposed to maintain a pollution free environment according to regulatory requirements.

Factory rules:

An employee should be careful, courteous, dignified in style and approach and maintain a decent relationship with his/her supervisor, other employees and be professional in dealing with colleagues.

An employee must be on time in attendance and discharging his/her duties.

An employee must not be inattentive without authorized leave.

Employee will refrain from smoking in the non-smoking area within the office and factory premise.

Employee should be truthful and be loyal to the organization.

Employee shall not have a direct or indirect economic interest that conflict with his/her duties and responsibilities.

Employee should be specific in cleanliness and tidiness.

Employee will refrain from willful con-compliance and insubordination, violent behavior during working hours.

Employee will catchphrase from using any XYZ properly such as vehicles, telephone, photocopies, office equipment etc. for unauthorized personal purpose.

Marketing

The process where the company generally generate their policy to specific product or group of products to the specific area of a country or whole country or the globe.

Conclusion of In plant training report

Although the Two weeks’ time of our training in XYZ Pharma Limited flew very quickly, with the co-operation of the authority and all the personnel, we have learnt a great and gathered a lot of experience which will be helpful for our future practical purposes. In every section, the respective authority cordially received us. They initiated our curiosity and interest regarding the relevant subjects. We are pleased with the behavior of every person involved in the factory. Thus, we have completed our training with great satisfaction and hope that the feeling is mutual.

The plant layout of the XYZ Pharma Limited plant at Bhaluka, Mymensingh in a word, excellent. It was, no doubt, a very well planned layout that provides an optimum use of space and ease of operation and thus contributes highly towards optimum productivity.

The plant is very well organized and the internal environment is very supportive to the employee, which is very nice since a congenial atmosphere increases the productivity of a company. The canteen is also very nice and the food menu was found to be very good, although there is always room for improvement in this regard.

One of the impressive things about XYZ Pharma Limited is its wide range of products and its quality. I was also very impressed with the maintenance of GMP and the extensive documentation of all the works kept in the in the company, complying with the ISO 9001 requirements.

Another most impressive things about XYZ Pharma Limited is that they are trying to commence such kind of product which are valuable and they are marketing it in lower price. For example the anti-cancer drug Enliven. I would like to end with a note of thanks, again, to Almighty Allah, and to everyone involved, for successful completion of this training and I hope that XYZ Pharma Limited will continue its co-operation to allow In-plant Training in future.

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Pan granulation mechanism, what do you mean by it?

Pan granulation mechanism: The mechanism of granulation process mainly divided into Dry Granulation and Wet Granulation. The formation of granules by Dry Granulation and Wet Granulation is totally different.

The conversion of powder to dry granules bed is totally different based of the machine used in granulation process, same as for Wet Granulation Process. The method of formation of granules in pan granulation mechanism can be described in different ways-

Pan granulation mechanism

Nucleation

In the presence of liquid/water a liquid bridges form an intact mass due to particle contact and adhesion which act as nuclei for further growth of granules. Presence of liquid, powder go through the stages act as nuclei.

Transition

The nuclei can be formed in two ways-One way is- where a single particle can be added to the nuclei and another is two nuclei can be add themselves and the resulted two nuclei reshape by the agitation of podwer bed.

Ball Growth

The resulting powder will grow in time to time and size increase of this spherical granules look like a ball. The ball growth process produces large granules, some this is too much large to use in pharmaceutical purposes. The spheronizing equipment like planetary mixer facilitate some degree of ball growth activities.

The ball growth process can be divided into four classes, stated here-

Coalescence

Two or more granules join together to form a larger granule.

Breakage

Granules are fragmented in to several parts and this parts joint in to another granules and form a layer over the existing granules.

Abrasion Transfer

When granules beds are facing agitation then attrition occur to the materials from granules, then this abraded materials attached/adhere to the other granules increase their size.

Layering

When we add one separate amount of powder to a granules bed then this powder adhere/attached to the granules form a granules layer over the surface and increase the granule size.  

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Particle Bonding Mechanism in granulation, What do you mean?

Particle Bonding Mechanism: 

The particles which form bond between themselves help to build up granules. So particle bond is essential to form effective granules which prevent breaking of granules during transportation. Particles are primarily form bond between themselves then number of particle form granules. There are several ways to form bond between the particles.

Particle Bonding Mechanism
Types of Particle Bonding Mechanism

In the context of granulation, particle bonding mechanism refers to the processes by which individual particles adhere to each other to form larger agglomerates or granules. Granulation is a process widely used in various industries such as pharmaceuticals, food processing, and fertilizer production to create granular materials with improved properties such as flowability, compressibility, and dissolution characteristics.

  • Several mechanisms contribute to particle bonding in granulation
  • Mechanical interlocking
  • Van der Waals forces
  • Capillary forces
  • Chemical bonding
  • Sintering
  • Electrostatic attraction

 

Mechanical interlocking:

 This process involves the physical entanglement of particles due to their irregular shape or surface properties. When particles come into contact, the irregularities mesh together and bonds form between adjacent particles.

Mechanical entanglement is an interesting phenomenon in which the irregular shape or surface properties of particles lead to physical entanglement. Imagine a scenario where you have a pile of Lego blocks. Each brick has a unique shape and surface texture, including projections, ridges, and edges. If you stack these bricks on top of each other, you will notice that they are not just stacked on top of each other. Rather, they are intertwined. Cracks in one brick lie over cracks in the other brick, forming a strong bond between the two bricks. This is a perfect example of a mechanical lock in action.

Also consider the structure of the Velcro. Velcro fasteners consist of two strips. One has a small ring (called the “male” side) and the other has a small ring (called the “female” side). When these strips are tied together, the loops on one side form a strong connection with the loops on the other side. This connection is purely mechanical and uses interlocking hooks and rings to hold the strips together.

Another example of mechanical interlocking in construction is the use of interlocking bricks or blocks. These bricks have a unique shape that allows them to fit together like puzzle pieces, creating a stable structure without the need for mortar or glue. The irregularities and projections on the surface of each brick mesh with adjacent bricks, preventing them from easily moving or separating.

Simply put, mechanical locks play an important role in many aspects of our daily lives, from simple activities like playing with LEGO bricks to more complex applications in design and manufacturing. This highlights the importance of understanding how the physical properties of materials can affect their behavior and interactions.

 

Van der Waals forces:

Van der Waals forces are weak attractions that exist due to temporary dipoles between molecules or particles. These forces can attract nearby particles to each other and contribute to particle bonding.

Van der Waals forces, named after Dutch scientist Johannes Diederick van der Waals, describe the weak but significant attractive forces that occur between molecules or particles. These forces arise from temporary fluctuations in the distribution of electrons within the molecule, resulting in temporary dipoles. Although van der Waals forces are weaker than ionic or covalent bonds, they play an important role in various phenomena such as the cohesion of liquids, the formation of molecular aggregates, and the adhesion of materials.

Let’s take the example of geckos, fascinating creatures known for their incredible ability to climb vertical surfaces and even walk upside down on rooftops. This extraordinary result is made possible by the complex interplay of van der Waals forces. Tiny hair-like structures called setae cover the gecko’s legs, and each bristle is divided into hundreds of smaller structures called spades. These spatulas create a large surface area, maximizing the potential for van der Waals interaction with the surface. When a gecko presses its paws against a surface, the weak van der Waals forces between the spatula and the surface combine to create an adhesive force that allows the gecko to cling tightly.

In everyday life, van der Waals forces also play a role in phenomena such as the condensation of a gas into a liquid, where molecules are held together by this weak attraction. For example, water vapor condenses in a glass of cold water, forming droplets due to van der Waals forces between water molecules. Similarly, coordination between molecules in liquid water is facilitated by surface tension and van der Waals forces, which contribute to the droplet forming ability.

Additionally, van der Waals forces are largely involved in interactions between molecules in biological systems. For example, the structure of DNA, the genetic blueprint of living organisms, is based, among other things, on the stacking of base pairs governed by van der Waals forces. Moreover, the folding of proteins into functional three-dimensional conformations is influenced by van der Waals interactions between amino acid side chains.

In summary, van der Waals forces may individually be weak, but their cumulative effects can be profound, shaping the behavior of molecules in a variety of situations, from the motion of a gecko to the structure and function of biological macromolecules.

 

Capillary forces:

Capillary forces arise due to the presence of liquid bridges between particles. When a liquid binder is added to the granulation process, it fills the voids between particles and creates liquid bridges. These bridges can solidify through processes such as evaporation or cooling, forming bonds between particles.

Capillary forces result from the formation of liquid bridges between particles, a phenomenon commonly observed in a variety of natural and industrial situations. For example, consider the granular process of pharmaceutical manufacturing. When a liquid binder, such as a solution of water and a polymer, is introduced into the dry powder mixture, it enters the spaces between the particles, effectively filling the voids and forming liquid crosslinks.

This process is similar to the way water flows through a sponge, sticking to the surface of the material and creating bonds between the fibers. In the granulation process, these liquid cross-links play an important role in shaping the properties of the final product. When the liquid binder penetrates the particle composite, it wets the surface, reduces interfacial tension, and promotes particle reorganization. This allows the powder mixture to dissolve into a cohesive aggregate.

Subsequent solidification of these liquid cross-links further solidifies the granular structure. This solidification can occur through a variety of processes depending on the type of liquid binder and environmental conditions. For example, if water acts as a binder, evaporation from heat or air flow will gradually remove the moisture, causing the liquid bridge to solidify and bond between adjacent particles. Similarly, in cooling processes such as freeze granulation, a drop in temperature causes the liquid binder to phase change from a liquid state to a solid state, causing the particles to stick together.

In essence, capillary forces and the addition of liquid binders ensure the coagulation of the granular material, allowing it to form a cohesive structure with appropriate properties. This phenomenon applies not only to the pharmaceutical industry but also to many other fields, from food processing and construction to ceramics and metallurgy. Manipulating particle interactions through liquid bridges is critical to achieving desired material properties and product performance.

 

Chemical bonding:

In some cases, chemical reactions may occur between particles or between particles and the binder. These reactions can form chemical bonds that provide strong adhesion between particles.

Chemical reactions can occur under a variety of conditions, particularly between particles or between particles and binders. These reactions are very important because they favor the formation of chemical bonds, creating strong adhesion between particles.

Consider the concrete curing process as a real-life example. When water is added to cement, a chemical reaction occurs between the water and cement particles to form hydrated calcium silicate gel (C-S-H). This gel acts as a binder and forms strong chemical bonds with the aggregate particles present in the mixture. As a result, concrete hardens and gains strength over time due to the chemical bonds formed between the components. This demonstrates how chemical reactions contribute to the cohesion and stability of materials, improving their structural integrity and performance in real-world applications.

 

Sintering:

An important process in materials science and manufacturing, sintering involves partial melting that occurs at the surface of particles when they are exposed to high temperatures. This heat treatment triggers a transformation step in which adjacent particles are exposed to heat and undergo surface liquefaction upon exposure, resulting in the formation of molecular bonds that bind them together.

To illustrate this concept, let us consider ceramic tile production. In the sintering stage of ceramic production, fine particles obtained from raw materials such as clay, silica and other additives are compressed into the desired shape. When these compressed particles are fired in a high-temperature furnace, typically in the range of 1,000 to 1,500°C, sintering is initiated by heat. At these high temperatures, the particle surfaces begin to soften and slightly melt, allowing intermolecular compounds to fuse and form. As a result, the separated particles gradually fuse to form a hard and dense ceramic structure. This process not only increases the strength and durability of ceramic tiles, but also helps develop desirable properties such as smoothness and uniformity of surface texture. Sintering therefore constitutes a fundamental technology for achieving the structural integrity and functional properties required for a wide range of industrial applications, from ceramics to metallurgy and beyond.

 

Electrostatic attraction:

Electrostatic forces can play an important role in particle bonding, especially in processes where particles become charged. Conversely, charged particles can attract one another and form bonds. Understanding and controlling these bonding processes is important to optimize the granulation process and achieve desired granulation characteristics such as size, shape, strength, and dissolution rate.

Electrostatic forces have a significant impact on particle bonding, especially in charged particle situations. When particles carry opposite charges, they exert a mutual attraction force, promoting bonding between particles. This phenomenon has wide application in various practical situations, such as granulation processes in pharmaceutical manufacturing.

Take tablet production as an example, where granulation is a critical step. In this process, powdered ingredients are combined and mixed with a binder to form granules. These particles must have specific characteristics such as size, shape, strength and dissolution rate to ensure the quality and effectiveness of the final product. During the granulation process, electrostatic forces are exerted when charged particles interact with each other. Conversely, charged particles are attracted to each other, promoting bonding and cohesion between particles.

Granulation Method Advancements

Understanding the complexity of electrostatic interactions and their impact on particle bonding is important for optimizing granulation processes. By controlling these bonding mechanisms, manufacturers can tailor particle properties to their desired specifications. This level of control allows the production of tablets with uniform active ingredient content, consistent dissolution profile, and improved bioavailability.

The same principles also apply to industries other than pharmaceuticals, such as ceramics or pesticide production. By using electrostatic forces to bind particles together, manufacturers can improve the quality, functionality, and performance of their products, ultimately meeting the diverse needs of consumers and industry.

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Maintenance of ETP [Effluent Treatment Plant]-SOP

Maintenance of ETP: This SOP [Maintenance of ETP] will make as per SOP for SOP of the respective company/Organization. Font/line spacing/Margin/Page set up/Header/Footer etc. will change as per requirement of SOP for SOP.

Maintenance of ETP

1.0 Purpose:

The purpose of this SOP is to define the standard procedure of preventive maintenance of Effluent Treatment Plant [ETP] of XX Pharmaceuticals Ltd.

2.0 Scope: 

This Standard Operating Procedure applies to the Effluent Treatment Plant [ETP] of XX Pharmaceuticals Ltd.

3.0 Definitions/Abbreviation: 

ACF: Activated Carbon Filter

ETP: Effluent Treatment Plant

MGF: Multi Grade Filter

PAC: Poly Aluminum Chloride

PPE: Personal Protective Equipment

SOP: Standard Operating Procedure

4.0 Responsibilities: 

Engineering Department [Validation]:

Preparing the SOP & revise it when required

Engineering Department [Maintenance]:

To provide essential support for maintenance of the system.

To ensure that the operators are accountable to carry out the maintenance.

Operators

To perform the maintenance activities according to the SOP.

Head of Engineering

To confirm that the maintenance of ETP are done correctly.

Head of Quality Assurance

To ensure overall implementation of this SOP.

5.0 Revision Details

Sl. No./Version No./Effective Date/Change History to be add here

6.0 Annexure:

Annexure has been mentioned in bottom of the document with download link

Annexure-I: Maintenance log sheet of ETP

7.0 Procedure:

7.1 Precautions: All maintenance activities must be done safely in accordance with the necessities of the Plant Safety Declaration and the safety notices from place to place the plant. Specific consideration must be paid to the following:

  • Handle the chemicals by wearing PPE.
  • Ensure that the pumps are switched off before initiating any kind of maintenance.

7.2 System Description:

The capacity of ETP is 5000 Liter/hour. The effluents from the production department come into the neutralization and equalization tanks via bar screen chambers. In this bar screen chamber the floating material/solid material is being filtered. A dosing of lime is being delivered in the neutralization tank if pH correction is needed.

The effluents are aerated in this tanks with air which is delivered by the blowers. After being neutralized in the neutralization tank the effluents goes into the equalization tank & then the effluent is relocated to the flocculation tank through effluent transfer pumping system.

 

A dosing of PAC [Poly Aluminum Chloride] is delivered in the flocculation tank to flocculate all the effluents. Poly electrolyte dosing [PED] is delivered in the transferring pipe of effluents from flocculation tank to the lamella.

After lamella the effluent is passed to the aeration tank. In aeration tank the effluents are aerated with air. A dosing of NaOH[Sodium Hydroxide] is provided if it is required.

 

There is a buffer tank after the aeration tank where 1kg of urea will be delivered after every Two months of operation. There is a line under the buffer tank to transfer the sludge to underground sludge tank & then to sludge pit by sludge transfer pumping system.

Clear water from the Buffer Tank is stored in the clear water tank. There are two pumps to transfer the clear water to final storage tank through MGF [Multi Grade Filter] & ACF [Activated Carbon Filter]. One pump is used at a time.

7.3 Maintenance Procedure:

7.3.1 Maintenance of ETP will be performed according to the following check list:

Type of maintenance: Daily

Maintenance activities:

  • Clean the screen bar daily.
  • Clean the surrounding environment of ETP.

Type of maintenance: Weekly

Maintenance activities:

  • Clean the control panel.
  • Check the electrical control panel and electrical connection.

Type of maintenance: After 2 months

Maintenance activities:

  • Clean the dosing tank.

Type of maintenance: After 3 months

Maintenance activities:

  • Change the oil of blower/compressor.

Type of maintenance: Yearly

Maintenance activities:

  • Clean all the tanks
  • Change the gear oil
  • Clean the clear water tank

7.3.2 Fill up the log sheet (Annexure-I) after performing preventive maintenance of ETP.

Annexure:

Annexure-I: Maintenance log sheet of ETP

Maintenance of ETP [Effluent Treatment Plant]-SOP Read More »

Preventive Maintenance Operation and Management System[SOP]

Preventive Maintenance: This SOP [Preventive Maintenance] will make as per SOP for SOP of the respective company/Organization. Font/line spacing/Margin/Page set up/Header/Footer etc. will change as per requirement of SOP for SOP.

Preventive Maintenance

1.0 Purpose: The purpose of this SOP is to describe the measures involved in conducting and managing preventive maintenance activities of the machines/equipment of XX Pharmaceuticals Limited.

2.0 Scope: This procedure applies to all machines/equipment of Production, Product Development [PD] and sampling area of every Blocks of XX Pharmaceuticals Ltd.

3.0 Abbreviation/Definitions

SOP: Standard Operating Procedure.

PM: The Preventive maintenance can be defined as to the routine maintenance which prevent the unwanted failure of any machine and keep the machine in working condition. The successful maintenance program prevent any type unwanted failure of running machine. To execute the successful maintenance program a schedule must be prepare and maintain the same.

4.0 Responsibilities:

The roles and responsibilities are described below:

4.1 Equipment Numbering and Database Maintaining

Validation Personnel [Engineering Department]

To maintain the Equipment Numbering System of the Equipment Database based on Excel Tracker.

To make the preventive maintenance proposal in accordance with the production planning.

To arrange the equipment list for Preventive Maintenance help of Maintenance engineer, comprising the maintenance intervals listed in respective section.

4.2 Setting up Preventive Maintenance for New Equipment

Head of Engineering/Designee

To ensure that all critical equipment’s are identified and are entered in the Equipment database.

To approve new Preventive Maintenance Planning and take initiative to if required changes to existing Preventive Maintenance Planning based on-

Equipment consumption.

Trending of maintenance antiquity (existing alike equipment).

Safety and legal necessities.

Discussion with the User, Technician and Engineering Executive

Merchant’s manuals and references

Engineering Executive

Inform the relevant departmental Head about the new routines and to ask appropriate time for Preventive maintenance prior to making PM Plan.

To update a list of spare parts based on the manufacturer’s references and to refer the list to the Planning and Procurement department [PPD] with a request to place order if required.

To support for arranging the PM schedule.

To check and ensure that the logbook is filled up by the technicians.

4.3 Preventive Maintenance Routine and Schedule

Maintenance Technician

To switch off the power and keep out the switch where the performing of maintenance activities does not involve any electrical connection and to retain the equipment entire time in lockout mode.

Before initiating the work, check the accurate equipment label has been attached to the equipment and it imitates to the equipment number based on the PM record datasheet.

To fill up the “PM record datasheet” upon accomplishment of activities.

Engineering Executive

To check and ensure that the “Preventive maintenance record datasheet” is filled up completely and to sign it upon completion of work.

To check that PM work is complete and to inform the area manager that the machine is ready for action.

4.4 Managing & Preserve Equipment Maintenance History File

Head of Engineering/Designee

To ensure that the PM planning table is kept up-to-date. If required, to refresh the schedule on a monthly basis or sooner.

To monitor the activities of the Engineering Executive performing the PM work and to provide technical support and assistance with documentation requirements. Also to ensure that PM work for particular equipment is completed within 30 days of scheduled PM date.

Validation Department [Engineering]

To uphold and preserve the equipment maintenance history files, maintenance instructions and associated documents at Engineering Department.

Head of Engineering/Designee

To confirm that the equipment maintenance history files are secured at Engineering Department.

4.5 Trend Analysis and Follow up Action

Head of Engineering/Designee

To check and review the history files of equipments maintenance annually and to find out the time of occurrence of major failures and to identify the repeated component of failures or other events.

5.0 Revision Details:

Sl. No. / Version No./ Effective Date/ Change History-will be se entitled in separate column.

6. Annexures:

List of Annex has been mentioned at the bottom of this document

7. Procedure:

Note: All maintenance work must be accomplished carefully in accordance with the necessities of the Plant Safety Declaration and the safety notices from place to place in the plant. Definite attention must be paid in the following:

a) Equipment must be electrically inaccessible and locked out where possible.

b) Personal Protective Equipment [PPE] and clothing suitable to the assign job must be worn.

7.1 All serious equipments must be acknowledged and PM processes must be set up with defined interludes and must be incorporate in the PM schedule.

7.2 PM plan is organized prior to performing the activities. For the production equipment this plan is prepared based upon the settlement with the Head of Plant Operations.

7.3 The lists of equipment/machine for preventive maintenance are to be provided in a separate Annexure. If any equipment/machine needs to be added or deducted from the list, Head of Quality Assurance/Designee will do it by hand writing it with signature with date without reviewing the entire SOP. The list will be restructured during next revision of this SOP.

7.4 There is a checklist included in the respective section for every equipment/machine which are undergone PM. The maintenance logbook of every equipment/machine will be store in the respective room and the technicians or engineering persons who are involved in doing the maintenance work will be liable to fill up the logbook upon close of the task. The forms will be store in the room of the respective machine in the shop floor.

7.5 “Under Maintenance”[Annexure-III]:  status label must be attached on the machine by the engineering personnel during preventive maintenance activities.

7.6 “Shifting in Progress for Maintenance”[Annexure-IV] status label must be placed by the engineering personnel on the machine at the time of shifting for maintenance activities.

7.7 Status label of “Preventive Maintenance” [Annexure-V] must be affixed by the engineering personnel on the machine after completion of preventive maintenance.

7.8 Photocopy of all approved forms to be used where easily applicable. Computer Generated form with exact format can be used with mentioning the following note at footer:

“This is a computer generated report and the format is as per the original approved form”

7.9 PM schedule [Annexure-I] must followed accordingly. The monthly preventive maintenance scheduling table should be circulated to the relevant department at the starting of every month and engineering department must keep a copy of the PM schedule.

7.10 Preventive maintenance schedule/plan may be changed if any requalification is carried out due to major modification or breakdown.

7.11 PM records/history[Annexure-II] must be reviewed to facilitate, evaluate and improving the performance of the PM programme and the performance of the Equipment/Machine.

7.12 Frequency/Interval of preventive maintenance schedule/Plan of a machine/equipment can be revised based on the frequency/interval and nature of breakdown happened in the past as per trending/trend analysis of the specific machine.

7.13 When the preventive maintenance of an equipment/machine is completed, successful trial will be run and the respective engineer will hand over/transfer/deliver the machine to the relevant departmental head/designee.

7.14 Maintenance activities of a number of equipment’s/machines:

The maintenance activities of various equipment’s/machines of XX Pharmaceuticals Ltd. are described here:

Fluid Bed Dryer:

Maintenance Interval: Monthly

Maintenance Task:

  1. Check the blower housing and drain for the possible condensate
  2. Check smooth operation of the blower
  3. Clean locking bolt using grease
  4. Check the Heat Exchanger
  5. Inspect All Screw Connection In-Process Piping System

Maintenance Interval: 6 Monthly

Maintenance Task:

  1. Check all O-Ring and adjustment if it is necessary
  2. Check the filter elements aimed at contamination
  3. Exchange filter elements, if there is any perceptible damage

Maintenance Interval: Yearly

Maintenance Task:

  1. Check the blower motor mount screws for tightness
  2. Check pneumatic inflatable gasket
  3. Check the all silicon gasket seals

Coating Machine:

Maintenance Interval: Monthly

Maintenance Task

  1. Check the pneumatic system
  2. Check and clean the pre filter
  3. Check the spray gun & air connection
  4. Check the pan motor, gear box drive belt
  5. Check the pan bearing & gear box bearing
  6. Check the door seal, pan bearing, hinges, and tightness
  7. Check the blower motor, blower housing & heat exchanger
  8. Check the solution mixing pneumatic motor and grease the bearings
  9. Check the flow switch, water solenoid valve, bar limit switch & hose retighten

Maintenance Interval: 6 Monthly

Maintenance Task

  1. Check the spray pump
  2. Check the Electrical Wire Connection
  3. Check the main gear box & gear oil level
  4. Grease the bearing and if it is damaged then replace the same

Yearly

  1. Check the gear oil level and add oil if it is necessary
  2. Check the door seals, pan bearing, coupler hinges and joints
  3. Check the blower motor and heat exchanger unit motor hose

Blister Machine:

Maintenance Interval: Monthly

Maintenance Task

  1. Check the Heater
  2. Check the Cam Bearing
  3. Check the Gear Oil Level
  4. Check the Electrical Connection
  5. Check the Pneumatic Connection

Maintenance Interval: 6 Monthly

Maintenance Task

  1. Check the Blade
  2. Check the Spring Tension
  3. Check the electrical connections
  4. Check the Roller Bearing & Bearing Pin

Maintenance Interval: Yearly

Maintenance Task

  1. Check the Air filter
  2. Check the Lubricated spring set
  3. Check the Gear oil and change if it is necessary
  4. Check the Oil spring set, if damage than change the same

Autoclave:

Maintenance Interval: 03 Monthly

Maintenance Task

  1. Check the door seal.
  2. Check the gasket of all TC clamp connections.
  3. Check for any lime build up in the vacuum pump discharge pipe.

Maintenance Interval: 06 Monthly

Maintenance Task

  1. Check the strainers fitted with the machines
  2. Check the pneumatic valve & solenoid valve seal and gasket
  3. Check the operational status of the non return valve fitted on sterilizer

Maintenance Interval: Yearly

Maintenance Task

  1. Check the all electrical connections
  2. Check the emergency button is working properly
  3. Visually check the condition of the mechanical chain
  4. Check the pneumatic cylinder opening/closing the door
  5. Visual check for any water leakage from the vacuum pump body

Encapsulation Machine:

Maintenance Interval: Monthly

Maintenance Task

  1. Check the Gear Oil Level
  2. Check the Vacuum Oil Level
  3. Check the Bearing Condition
  4. Check the Electrical components
  5. Check the Main Motor Connections
  6. Check the Powder Sensor Sensitivity

Maintenance Interval: Half Yearly

Maintenance Task

  1. Refill Vacuum Oil if necessary
  2. Check Gear Oil and change if necessary

Bottle Washing Machine:

Maintenance Interval: Monthly

Maintenance Task

  1. Check the filters
  2. Check the gear box
  3. Check the float switch
  4. Check the pneumatic line
  5. Clean the electrical panel board
  6. Check the nozzle and clean it if necessary

Maintenance Interval: 3 Monthly

Maintenance Task

  1. Check the Gear oil level
  2. Check the bearing condition
  3. Check the main motor connection
  4. Check the electrical all components

Maintenance Interval: 6 Monthly

Maintenance Task

  1. Check the Gear oil and change the same if required.

Conveyer Belt:

Maintenance Interval: Weekly

Maintenance Task

  1. Check the main motor
  2. Check the roller bearing
  3. Check the gear box with oil
  4. Check the roller adjustment belt
  5. Check the chain, clean and grease

Maintenance Interval: Monthly

Maintenance Task

  1. Check the Gear oil level.
  2. Check the electrical all component.

Maintenance Interval: Yearly

Maintenance Task

1. Check and change gear oil if it is required.

De-duster Machine:

Maintenance Interval: Weekly

Maintenance Task

  1. Check the main motor
  2. Check the roller bearing
  3. Check the gear box with oil
  4. Check the roller adjustment belt
  5. Check chain and clean and grease

Maintenance Interval: Monthly

Maintenance Task

  1. Clean the Electrical panel board.
  2. Check the gear oil and change, if it is needed.

Blending Machine:

Maintenance Interval: Monthly

Maintenance Task

  1. Check all safety interlock and mechanisms.
  2. Check the machine for irregular noise or vibration.
  3. Check compressed air filter and clean/change if required.
  4. Check Pneumatic System (Air Condition Filter and Regulator)

Maintenance Interval: Yearly

Maintenance Task

  1. Check the double cone tool
  2. Clean the electrical cabinet sensibly
  3. Check the Gear Oil Level If need then replace
  4. Check for any unfamiliar noise or shaking from the machine

Two Head Liquid Filling Machine:

Maintenance Interval: Monthly

Maintenance Task

  1. Check the roller bearing
  2. Check the gear box with oil
  3. Check the piston and the disks
  4. Check the main motor with v-belts
  5. Check and grease all movable parts

Maintenance Interval: 6 Monthly

Maintenance Task

  1. Check the overall cleaning
  2. Check the electrical all component
  3. Check the pistons and disks for any damage

Manufacturing Vessel:

Maintenance Interval: Monthly

Maintenance Task

  1. Check gear box with oil
  2. Check main motor with V-belt
  3. Check roller bearing of the pump
  4. Check and grease all movable parts
  5. Check the transfer pump of the vessel

Maintenance Interval: half Yearly

Maintenance Task

  1. Check the overall cleaning
  2. Check the electrical all component
  3. Check the mechanical seal of the pump

Tablet Compression Machine:

Maintenance Interval: Monthly

Maintenance Task

  1. Check the V-belt
  2. Check the main shaft
  3. Check the warm gear
  4. Check the pressure roller
  5. Check the electrical cabinet
  6. Check the pressure adjust knob

Maintenance Interval: 6 Monthly

Maintenance Task

  1. Check the filling depth
  2. Check the Gear oil level
  3. Check the hydraulic oil level
  4. Check the electrical connection
  5. Check the powder level sensor

Maintenance Interval: Yearly

Maintenance Task

  1. Check the Gear oil viscosity
  2. Check the electrical component
  3. Check the Hydraulic oil if need replace it

Cap Sealing Machine:

Maintenance Interval: 6 Montly

Maintenance Task

  1. Check the gear oil level
  2. Check the cap sealing holder
  3. Check the motor piston with grease
  4. Check the pressure adjustment knob
  5. Check the bearing with gear premium

Maintenance Interval: Yearly

Maintenance Task

  1. Check the pneumatic motor
  2. Check the electrical cabinet
  3. Check the pressure adjustment knob
  4. Check the motor with bearing piston grease
  5. Check the gear oil level if need change the same

Stability Chamber:

Maintenance Interval: Monthly

Maintenance Task

  1. Clean the PT100 Sensor
  2. Check the door pipe connection
  3. Check the chamber door closing
  4. Check the operations of safety thermostat
  5. Check the condenser fan, if found loose then tighten it
  6. Check the proper earthling connection to the stability chamber

Maintenance Interval: Half Yearly

Maintenance Task

  1. Check the evaporation tray
  2. Clean the condenser by blower air through
  3. Check the water immersion heater and reservoir tank
  4. Check the side port hole is properly fitted with rubber cork

7.14.16 Rapid Mixer Granulator of Product Development:

Maintenance Interval: Monthly

Maintenance Task

  1. Check the pneumatic component
  2. Check the electrical wire connection
  3. Check any unusable noise or vibration
  4. Check all safety interlock and mechanism

Maintenance Interval: 6 Monthly

Maintenance Task

  1. Check the electrical wire connection
  2. Check the oil level and viscosity of oil manually

Rapid Mixer Granulator of Product department:

Maintenance Interval: Monthly

Maintenance Task

  1. Check the main motor with gear
  2. Check the chopper motor bearing
  3. Check the impeller and motor bearing condition

Maintenance Interval: 6 Monthly

Maintenance Task

  1. Check the Electrical Wire Connection
  2. Check the V-Belt & Motor Condition
  3. Check the Mechanical Seal or Bearing
  4. Check the Main Gear Box Gear Oil Level

Maintenance Interval: Yearly

Maintenance Task

  1. Check the discharge valve’s motor condition.
  2. Check the gear oil level if it is needed then replace the same.

Sampling Booth:

Maintenance Interval: fortnightly

Maintenance Task

  1. Clean the pre filter (G4).
  2. Check the motor condition.
  3. Check the machine’s all nuts and bolts.

Maintenance Interval: Monthly

Maintenance Task

  1. Clean blower motor.
  2. Check electrical constituents & motor.
  3. Check for any unfamiliar noise or vibration.

Dispensing Booth:

Maintenance Interval: Forthightly

Maintenance Task

  1. Clean pre filter (G4).
  2. Check the motor condition.
  3. Check the machine’s all nuts and bolts.

Maintenance Interval: Monthly

Maintenance Task

  1. Clean the blower motor.
  2. Check electrical components and motor.
  3. Check for any unfamiliar noise or vibration.

Solution Mixing Tank:

Maintenance Interval: 6 Monthly

Maintenance Task

  1. Check the baffle plate
  2. Check the pneumatic motor
  3. Check the pressure adjustment knob
  4. Check the pneumatic motor piston grease

Maintenance Interval: Yearly

Maintenance Task

  1. Check the baffle plate
  2. Check the pneumatic motor
  3. Check the Pressure Adjustment knob
  4. Check the pneumatic motor piston grease

Vacuum Pump

Maintenance Interval: Fortnightly

Maintenance Task

  1. Clean the filter
  2. Clean the O ring
  3. Check the nut bolt
  4. Check the motor condition

Maintenance Interval: Yearly

Maintenance Task

1. Clean the blower motor

2. Check the electrical all component and motor

Vibratory Shifter:

Maintenance Interval: Monthly

  1. Maintenance Task
  2. Check housing flange
  3. Check the motor body
  4. Check the motor flange
  5. Check electrical Components

Maintenance Interval: 6 Monthly

Maintenance Task

1. Check the motor electrical connection

2. Check the motor bearing house with bearing

Powder filling machine:

Maintenance Interval: 6 Monthly

Maintenance Task

  1. Check airline
  2. Check gear box
  3. Check all grease point
  4. Check all pulley and Belt
  5. Check vibration and abnormal noise
  6. Check all screws on driving units, tighten it if necessary

Maintenance Interval: Yearly

Maintenance Task

  1. Check the earthing
  2. Check the switches
  3. Check voltage and frequency

Sticker Labeling Machine:

Maintenance Interval: Monthly

Maintenance Task

  1. Check the pneumatic system
  2. Lubricate the motor bearing as needed
  3. Check all screws on driving units & tighten it if required

Maintenance Interval: Yearly

Maintenance Task

  1. Check the earthing
  2. Check the inverter connection
  3. Check the voltage & frequency
  4. Check the electrical control unit

Automatic Dehumidifier:

Maintenance Interval: Monthly

Maintenance Task

  1. Check the fan.
  2. Check for somewhat leakage
  3. Check the cooling coil
  4. Check the gas pressure of the compressor
  5. Remove the condenser water from container
  6. Check the screw on driving units & tighten it if needed

Maintenance Interval: Yearly

Maintenance Task

  1. Check the electrical switches
  2. Check the electrical connections

Tablet De-duster:

Maintenance Interval: Monthly

Maintenance Task

  1. Check the main motor
  2. Check the gear oil level
  3. Check the roller bearing
  4. Check the gear box with oil
  5. Check the roller adjustment belt
  6. Check the electrical all component
  7. Check the chains and clean & grease

Maintenance Interval: Yearly

Maintenance Task

  1. Check the electrical panel board & overall cleaning
  2. Check the viscosity of gear oil & change it if necessary

Inkjet Printer:

Maintenance Task

Maintenance Interval: Monthly

  1. Check the vacuum pump
  2. Check the ink spray needle
  3. Check the electrical cabinet
  4. Check the solvent or ink status
  5. Check the pressure adjust knob
  6. Check the main ink head of printer

Inkjet Printer:

Maintenance Task

Maintenance Interval: Monthly

  1. Check the main head
  2. Check the vacuum filter
  3. Check the ink expire date
  4. Check the electrical connection
  5. Check the ink or solvent level sensor

Vial Washing Machine:

Maintenance Interval: Monthly

Maintenance Task

  1. Check the Nozzle
  2. Check the Gear Box
  3. Check the Float Switch
  4. Check the Pneumatic Line
  5. Check the Electrical Panel Board
  6. Check the Pneumatic Line, Connector & Filter

Maintenance Interval: 3 Monthly

Maintenance Task

  1. Check the Gear Oil Level
  2. Check the Hot Water Line
  3. Check the Bearing Condition
  4. Check the Main Motor Connection
  5. Check the Electrical All Component
  6. Check the Powder Sensor Sensitivity
  7. Check the Turret and Moving Parts Clean and Grease

Maintenance Interval: 3 Monthly

Maintenance Task

  1. Change the Gear Oil
  2. Refill the Vacuum Oil
  3. Clean the Overall Machine

Multi Mill:

Maintenance Interval: Monthly

Maintenance Task

  1. Check the pulley
  2. Check the hopper will blades
  3. Check screws on driving units, tighten it if required

Maintenance Interval: Yearly

Maintenance Task

  1. Check the earthing
  2. Check the inverter connection
  3. Check electrical switches
  4. Check the electrical control unit
  5. Check the voltage and frequency

List of  Annexures:

Annexure-I:   Schedule for Preventive Maintenance of Equipment

Annexure-II:  Record Data Sheet for Preventive Maintenance

Annexure-III: Status label “Under Maintenance”

Annexure-IV: Status label “Shifting in Progress for Maintenance”

Annexure-V: Status label of “Preventive Maintenance”

Preventive Maintenance Operation and Management System[SOP] Read More »

Breakdown Maintenance SOP for Engineering Department

Breakdown Maintenance: This SOP [Breakdown Maintenance] will make as per SOP for SOP of the respective company/Organization. Font/line spacing/Margin/Page set up/Header/Footer etc. will change as per requirement of SOP for SOP.

Breakdown Maintenance

1.Purpose

The purpose of this SOP is to define the procedures involved in conducting and handling breakdown maintenance activities of the equipments/machines of XX Pharmaceuticals Limited.

2.Scope

This Standard Operating Procedure applies to all equipments/ machines of GMP all area of XX Pharmaceuticals Ltd.

3.Definitions / Abbreviation:

  • BM: Breakdown Maintenance
  • SOP: Standard Operating Procedure
  • QA: Quality Assurance

4. Responsibilities

The responsibilities are as follows:

Initiating Department:

  • To inform Quality Assurance, Head of Plant Operations and Engineering Department for the breakdown maintenance of linked equipments, machines or utility rest area.
  • To fill up the breakdown maintenance memo and backup the carbonated copy.
  • To put the status label “UNDER MAINTENANCE” on the machine.
  • To check related machines, equipments or utility services along with Quality Assurance personnel after completion of BM Activities.

Engineering Department/Maintenance Department

  • To receive the BM Memo and arrange for be present the breakdown maintenance.
  • To assess the cause of breakdown and resolve the problems.
  • To oversee the BM job and update necessary record.
  • To fill up the BM History form for each machine after completion of Breakdown Maintenance.
  • To preserve the BM related documents.

Technician

  • To execute the breakdown maintenance by following the appropriate safety precautions

Quality Assurance

  • To evaluate and select disposition or further operation of products/batches under bearing
  • To inform Validation Department [Engineering End] to perform requalification or recalibration of the machine/equipment if it is required.
  • To certify that actionable and recommendation are closed.

Validation Department (at Engineering End)

  • To perform requalification or recalibration of the equipment/machine if it is necessary.
  • To issue the Breakdown Maintenance Memo for the individual sections.

Head of Engineering

  • To monitor actions of engineering personnel who perform the Breakdown Maintenance activities and to provide technical provision and assistance with documentation supplies.
  • To assessment the history files of equipment’s maintenance annually and at the time of incidence of major failures and to identify the repeated component of failures or other events.
  • To confirm that the equipment maintenance history files are secured in the Engineering Department.

Head of Quality Assurance

  • To confirm overall implementation of this SOP

5.Revision Details

  • Sl. No./ Version No./ Effective Date/ Change History to be add here

6. Procedure

Precautions: All maintenance work must be accomplished safely in agreement with the requirements of the Plant Safety Declaration and the safety notices around the plant. Specific consideration must be paid to the following-

Personal Protective Equipment [PPE] and clothing appropriate to the job must be worn.

Equipment must be electrically inaccessible and locked out where potential.

“Under Maintenance” status label must be attached on the machine during BM activities.

“Shifting in Progress for Maintenance Work” status label must be attached on the machine at the time of shifting for maintenance activities.

6.1 Concerned Department

6.1.1 In case of equipment, machine or utility breakdown, the related departmental personnel will label it with ‘UNDER MAINTENANCE’ status label.

6.1.2 The BM Memo will be a pre-printed, bi-layer, self-carbonated paper which will be filled up by the related departmental personnel and the original copy will be sent to the Engineering Department to evaluate and be present at the problem. The carbonated copy will be store by the relevant department.

6.1.3 The pre-printed serial no. of each page of “BM Memo” will be considered as the “BM Memo” number.

6.2 Quality Assurance Department

6.2.1 Quality Assurance personnel would estimate the breakdown to assess the influence on product quality, safety, efficacy matters and take decision whether the product would be disposed.

6.2.2 Quality Assurance will inform the Validation Team [at Engineering End] after completion of breakdown maintenance to execute the requalification or recalibration of that machine if it is necessary.

6.2.3 Quality Assurance may hold the production batches if any harmful impact occurs till further study.

6.3 Engineering Department

7.3.1 Engineering personnel will receive the “BM Memo” and evaluate the reason and resolve the problems.

6.3.2   Before initiating the maintenance activities, detach unwanted services [‘LOTO Procedure’ to be followed] from the safety point of view.

The breakdown maintenance activities will be carried out according to the equipment handbook (if required) under the supervision of maintenance supervisor/Line In-charge.

6.3.3 A tag “Shifting In Progress For Maintenance” will be put on the machine during shifting to the workshop for maintenance Activities.

6.3.4 After completion of BM activities, relink the utility services and take the usage trial in presence of relevant departmental personnel and Quality Assurance personnel. After successful trial, engineering department will deliver the machine to the relevant department.

6.3.5 Engineering department shall assess the need for requalification or recalibration in discussion with Quality Assurance and document the identical in the memo. Quality Assurance in turn shall inform to production and validation team[at Engineering End] for recalibration or requalification.

6.3.6   Preventive maintenance calendar can be changed based on the rate of breakdown of a specific machine.

6.3.7 Engineering department will maintain the data record of the breakdown activities with trend analysis.

6.3.8 After finishing the breakdown maintenance activities engineering/maintenance person will fill up the “Breakdown Maintenance History Form” of that “Machine/Equipment/System” and store all breakdown related documents in Engineering Department.

6.3.9 If the Area is out of any possible harm and found okay, routine operation will be started after Quality Assurance Inspection with adequate cleaning.

6.3.10 Photocopy of all approved forms will be used. Computer generated copies of all related form can be used with proper note, mentioning in the footer-

‘’This is the computer generated form and similar in that of original form”

8. Annexure [Downloadable File Available]

Annexure-I:   Breakdown Maintenance Memo.

Annexure-II: Breakdown Maintenance History form.

This all about the SOP for “Breakdown Maintenance”. This is the basic process and may be change based on company policy [but not limited to].

Breakdown Maintenance SOP for Engineering Department Read More »

Audit Checklist for QA Department in Pharmaceutical Company

Audit Checklist for QA Department: here is the Audit Checklist for QA Department. You can find the best checking point for QA [Quality Assurance] Department in pharmaceutical Company-

Audit Checklist for QA
  1. Annual product review/Product Quality Review reports
  2. Batch Document Archiving /Retrieval system/Disposal records
  3. CAPA [Corrective And Preventive Action]
  4. Calibration Records of balance, equipment’s, machine etc.
  5. Change Control
  6. Destruction of samples & Chemicals reports
  7. Deviation Management
  8. Drug Master file of existing & new products
  9. Failure Investigation
  10. Finished products Released records
  11. GMP/Self-Inspection audit reports
  12. Job Description
  13. Incineration by third party Records
  14. List of finished products, Raw materials & packing materials
  15. Logbook maintaining & Issuance Records
  16. Label Control Procedure
  17. Market Complaint Investigation Report
  18. Machine/Equipment Qualification status records with index
  19. Organogram (Factory)
  20. Previous Self Inspection/Internal Audit Report
  21. Process Validation Protocols & reports
  22. Quality Manual
  23. Risk Management
  24. Retention Sample Management
  25. Rework/Re-process records
  26. Reagent Management records with index
  27. Recall Procedure
  28. Retention samples records with index
  29. Records of market return Goods destruction
  30. Site Mater File (SMF)
  31. Source approval procedure and its records
  32. Standardization of volumetric solution records
  33. Stability studies report of both accelerated and long term
  34. Storage condition of RM, PM, intermediate, bulk & finished products
  35. Specimen signature list
  36. Technology transfer records
  37. Validation Master Plan (VMP)
  38. Vendor/ Supplier Audit reports
  39. Write off & Disposal records of Non-conforming/Rejected materials & products
  40. Yearly Training Calendar and its records for both on Job & GMP
  41. SOP Index
  42. SOP for
  • CAPA
  • Change Control
  • Deviation Management
  • Hold Time Study
  • IPC[In-Process Control] Instruments
  • Job Description
  • Labelling & Label Control
  • Market Complaint Handling
  • Quality Manual
  • Quality Risk Management[QRM]
  • Recall Procedure
  • Site Master File
  • Training Manual
  • Waste Disposal

This all about the Audit Checklist for QA Department but not limited to.

Audit Checklist for QA Department in Pharmaceutical Company Read More »

Selection and recruitment of Manpower by the HRD[SOP]

Selection and recruitment of Manpower: This SOP [Selection and recruitment of Manpower] will make as per SOP for SOP of the respective company/Organization. Font/line spacing/Margin/Page set up/Header/Footer etc. will change as per requirement of SOP for SOP.

1.Purpose

The purpose of this SOP is to lay down the right selection and recruitment of the Manpower as per Approved Requisition From the department through a systemic process.

2.Scope

This SOP is applicable for the all employees of the XX Pharmaceuticals Limited.

 

3.Definitions / Abbreviation
Selection

Sorting of Curriculum Vitaes (CVs) as per company policy  then arrange Written / Oral Examination for the preliminary selected Candidate and finally prepare Merit List based on their interview[Both Written / Oral]. Sending this Merit List to the Managing Director for his valuable comments.

Recruitment

After final review by the Honorable Managing Director, discuss the facility matters with the above Listed Candidates in presence HRD Manager, Hiring Manager & Respective Department Representative [SME, Subject Matter Expert]. When both party end closer to a conclusion, Appointment Letter will be issued with Employment Agreement.

4.Responsibilities:

The roles and responsibilities are as follows:

Executive / Sr. Executive, HR & Admin:

To share the necessary format.

Head of Plant Operation:

To share the necessary format.

To brief the importance of this activity.

To implement this correctly

Head of Quality Assurance:

To approve the SOP

5.Revision Details:

Version No.00

Effective date: 22/05/20XX

Change History: New SOP

6.Annexure

Annexure I- Manpower Requisition Form

Annexure II-Evaluation Sheet for Interviewing Person.

7.Procedure

7.1 Raise the Prerequisite of Manpower by checking its need with proper explanation from the         Department Head and needs to be referred to the Head of the HR & Administration as hard copy.

7.2 After receiving, the Head of HR & Administration will forward that prerequisite with a note to the Honorable Managing Director.

7.3 Arrange a circular on the basis of the need duly approved by the Managing Director for the online and offline National/International Media based on company requirement.

7.4 After circulating the prerequisite, collect CVs of multiple applicants on receiving file them accordingly and store them in a proper location.

7.5 After the due date of circular, sorted out all of them and get ready summary list for the commendable candidates, then submitted to the Managing Director for the permission of interview.

7.6 Arrange a formal Interview in the presence of the concern Head of the Department/Designee, related person from cross functional department and the Head of Human Resource/Designee.

7.7 After the completion of interview session, get ready the summary list of the appropriate and overall acceptable candidates with marking (Scale: 0~5). To sum up, submit it to the Managing Director for review and final comments for the next necessary actions.

7.8 Then, Head of HR & Administration/Designee will go for contacting the selected candidate to discuss & finalize the facility issues.

7.9 In conclusion, Head of HR & Administration will take subsequent actions for joining the required personnel on due date.

8.Associate documents

Mention the linked document here

9.References

Mention reference here

This all about the SOP for “Selection and recruitment of Manpower”. This is the basic process and may be change based on company policy [but not limited to].

Download the Annexure Here

Annexure I- Manpower Requisition Form

Annexure II-Evaluation Sheet for Interviewing Person

Selection and recruitment of Manpower by the HRD[SOP] Read More »

Audit Checklist for HR Department in Pharmaceutical Company

Audit Checklist for HR Department: here is the Audit Checklist for HR Department. You can find the best checking point for HR [Human Resources] Department in pharmaceutical Company-

Audit Checklist for HR Department
  1. Career Development Programme
  2. Company business strategy
  3. Company Policy
  4. Control of Entry with illness and open lesion
  5. Cleaning and sanitization records
  6. Departmental Organogram
  7. Dust control and Management Record
  8. Employee list of Organization
  9. Employee Retention Programme
  10. Environment Health and Safety Programme
  11. Entry/Exit Register Management
  12. Final Settlement Procedure
  13. Firefighting System
  14. Fire drill Programme
  15. Human Resources Programme
  16. Handling of laundry procedure
  17. Handling of sewage during production factory
  18. Handling of Accidental hazard and record keeping
  19. Handling of ETP sludge
  20. Identification of Fire Assembly Point
  21. Induction Training Record
  22. In-plant training Management
  23. Job description of Employee
  24. Leave Management Process
  25. Leave Management Process
  26. List of First Aid Item
  27. List of Departmental SOP
  28. Manpower Development Plan
  29. Medical Checkup process for new comer
  30. Previous Audit Report and Incomplete Action Plan List
  31. Pest and Rodent control procedure
  32. Recruitment Process
  33. Short leave/Emergency Leave Register
  34. Training Need Assessment
  35. Yearly Training Calendar
  36. Waste Management Procedure

SOP on

  1. Canteen Facility Management
  2. Charge Hand Over and Take Over of Security Department
  3. Cleaning Procedure for Insects Killer
  4. Company Policy for Visitors
  5. Dress Coding System and Gowning Procedure for Working Personnel and Visitors
  6. Employee Motivation
  7. Entry & exit procedure
  8. Factory gowning management
  9. Factory Gowning Cleaning and Management Procedure
  10. First Aid Kit Management Procedure
  11. House-Keeping and Cleanliness
  12. Induction of the New Employee
  13. Laundry Procedure for Working Dresses
  14. Medical Examination of the Working Personnel
  15. Measures for the Working Personnel at the Plant
  16. Management of Personal Protective Equipment (PPE)
  17. Occupational Health and Safety
  18. Organizational Behavior
  19. Process of Pest and Rodent Control at the Plant Premises
  20. Sanitizing Procedure for Sink and Floor Drain Sanitization
  21. Security Awareness
  22. Selection and Recruitment of Manpower
  23. Training of Employee

This all about the Audit Checklist for HR Department but not limited to.

Audit Checklist for HR Department in Pharmaceutical Company Read More »

Audit Checklist for IT Department in Pharmaceutical Company

Audit Checklist for IT Department: here is the Audit Checklist for IT Department. You can find the best checking point for IT [Information Technology] Department in pharmaceutical Company-

audit checklist for IT Department
  1. CD and Software List
  2. Departmental Organogram
  3. Departmental Objective
  4. Data backup schedule with frequency
  5. Installed Software list for different equipment’s
  6. IT policy and its application
  7. List of technical personnel and their training Certificate
  8. List of Approved Password for user and Administrative Password for System control
  9. List of Password Management for Emailing Account [Including Outlook and Webmail like Zimbra web client]
  10. Personal Computer list with ID
  11. Preventive Maintenance schedule for PC’s and Laptop
  12. Service Record Keeping Logbook
  13. Update Antivirus Software List
  14. Valid Certification for Installed Software

This all about the Checklist for IT Department but not limited to.

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Audit Checklist for Engineering Department and Maintenance Department

Audit Checklist for Engineering Department: Here is the tentative Audit Checklist Engineering Department. You can follow the checking point during auditing process at Engineering and Maintenance Department.

Audit Checklist for Engineering Department
  1. Approved Departmental Organogram.
  2. Area monitoring for Temperature/Relative Humidity/Differential Pressure.
  3. BMS[Building Management Systems] Operation Record Logbook/Data Backup/Data storage/Authorized User List
  4. Breakdown Maintenance Record.
  5. Boiler Certificate and Boiler Operator Registration Number.
  6. Buffer stock of Filter with identification Mark.
  7. Calibration Tag with due date on equipment’s.
  8. Compressed Air Validation Record.
  9. Deviation Management Record.
  10. Departmental Objective.
  11. Dust collector SOP, Record, Disposal and Operation Logbook.
  12. Drawing of Technical Floor and Production Floor[With Man/Machine Flow].
  13. Equipment’s Calibration schedule with frequency.
  14. ETP process flow diagram.
  15. Filter Integrity Test Record.
  16. Filter Changing record.
  17. HVAC Validation Record.
  18. Incinerator Operation Logbook/Third party agreement for Incineration.
  19. IQ, OQ, PQ record for new equipment’s.
  20. List of Personnel and their Job description.
  21. List SOP’s.
  22. List of Equipment’s.
  23. List of Spare Parts.
  24. Labelling of all critical machine/Line/Instruments e.g. Boiler, Underground Water Line, Diesel Tank, Gas Cylinder etc.
  25. Logbook for Operation of ETP.
  26. Marking of Clean and Unclean Filter.
  27. Maintenance & Service Card/Record
  28. Personal Protective Equipment list for maintenance of any equipment’s.
  29. Previous Audit Report.
  30. Previous Audit Pending Issue.
  31. Preventive Maintenance Schedule.
  32. Record keeping during CAPA procedure.
  33. Retention Time of documents.
  34. RSD[room schematic diagram] and RDS[Room Data Sheet] record.
  35. Sanitation Record of Water system.
  36. SOP for LOTO [Lock Out, Tag Out] Procedure.
  37. SOP for Color Code.
  38. SOP display on working place/Area/Machine Location.
  39. Status label for equipment’s/Critical Spare parts/ Clean Filters.
  40. Storage Record of critical Spare Parts.
  41. Third party Agreement for Calibration of Equipment’s.
  42. Training Record of Personnel.
  43. Training Need Assessment.
  44. Temperature Mapping.
  45. Under Maintenance /Under Installation/Out of order Identification Label.
  46. Yearly Calibration Schedule with frequency.
  47. Yearly Training Calendar.
  48. Work Permit Record for equipment’s maintenance.
  49. Water System Drawing with user point identification.
  50. Water sampling point Identification.

This all about the Audit Checklist for Engineering Department [but not limited to]. You can treat this list as Internal Audit/ Self-Inspection Checklist or any checklist to find out the lacking of respective department.

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Audit Checklist/Self Inspection Checklist for Quality Control Department

Audit Checklist: Here is the tentative Audit checklist [Internal Audit/Self Inspection Checklist] for Quality Control Department. You may follow the below list at the time of Audit [Internal Audit/Self Inspection] for Quality Control Department-

1. Approved Departmental Organogram.

2. Approved vendor List of Raw and Packaging Materials.

3. Acceptance Record of Raw Material and Packaging Material.

4. Approval or Rejection of Materials and Products.

5. Controlling method of  

  • Purchase
  • Primary Packaging and   
  • Printed Packaging Materials

6. Data Verification based on Logbook and Chromatograms.

7. Document retrieval and achieving Procedure.

8. Collection of retained sample and retrieval system.

9. Certificate of analysis.

  • Primary data
  • Checking of calculations
  • Preservation of primary data

10. Certification of Products for Release.

11. Chemical Reagents consumption records.

12. Calibration Record Keeping for the instruments.

13. Calibration schedule/calendar of instruments.

14. Disinfectant effectiveness testing based on different concentration.

15. Documentation

  • Material receiving report
  • Preservation of original data
  • Final report
  • Communication with related department e.g- Supply chain, Warehouse, Accounts

16. Health checks for all personnel

  • Pre-employment
  • Yearly
  • Record

17. In-process analysis (Specification & method)

  • Currently revised
  • Revision procedure
  • Validation
  • Approval

18. Instruments SOPs of operation, maintenance & calibration

  • Operation Logbook
  • Calibration
  • Servicing
  • Documentation

19. Investigation of Test Failure.

20. Job Responsibilities of all personnel are available.

21. List of Reagents & Solvents.

22. Laboratory Reagents

  • Identified
  • Tested
  • Expiration dated

23. Maintaining of Reference Number for

  • Specification
  • Starting materials (both RM & PM)
  • Finished products
  • Certificate of Analysis

24. Management of HPLC columns.

25. Method for Identification of each starting materials container.

26. Management of Working Standard/Reference Standard.

27. Management of analytical worksheets.

28. Method Validation of Testing Product.

29. Maintain and storage of HPLC Column and column suitability test.

30. Management of Control Sample.

31. Practice and Record keeping of OSS with action plan.

32. Personnel engaged in analytical activity.

  • Personnel Hygiene
  • Lab Coat

33. Prohibited in working area

  • Smoking
  • Chewing tobacco
  • Eating/ Drinking

34. Preparation and record keeping of working standard and volumetric solutions.

35. Record Keeping of

  • Sampling
  • Inspection and
  • Testing procedures

36. Reference Standard

  • Evaluation
  • Maintaining
  • Record Keeping
  • Logbook Entry
  • Storage

37. Receiving Record of

  • Reagents
  • Chemicals
  • Culture Media

38. Retesting procedure

39. Received Material

  • Sampling Plan
  • Sampled Quantity

40. Real Time & On-going Stability Study Calendar/Schedule.

41. Qualification [DQ, IQ, OQ & PQ] records of Oven.

42. Real Time & On-going Stability Study Sample Receiving Record.

43. Real Time & On-going Stability Study Failure Investigation.

44. Real Time & On-going Stability Study Report Evaluation, Recommendations and Conclusion.

45. Safety

  • Fire extinguishers-adequacy
  • First aid-adequacy
  • Possibility of potential electrical hazards

46. SOP on cleaning

  • Glass apparatus
  • General cleaning of department

47. SOP on Material Coding System.

48. SOP on calibration of measurement equipment.

49. SOP on Handling of breakdown of stability chambers.

50. SOP for sampling of

  • Starting Materials
  • Bulk Materials and
  • Finished Products

51. SOP for

  • Label and labeling system
  • Packing Materials handling
  • Handling of the raw material
  • Reanalysis
  • Testing of Market Complaints Sample
  • Testing of Recalled Products
  • Return products

52. Stability study

  • List of products under stability study
  • Stability protocols & reports
  • Temp. % RH monitoring records of the stability chambers

53. Shelf life extension programme based on Real Time Stability Study.

54. Stability Study Record of Primary packaging materials.

55. Standardization of volumetric solution & documentation.

56. SOP for Sampling and Management of Raw Materials, Packaging materials.

57. Sampling of Water System.

58. Specification & Methods

  • Currently revised
  • Revision procedure
  • Validation
  • Approval

59. Standard Lab requirement availability

  • Adequate facilities
  • Trained persons
  • Analyst Validation
  • Approved procedures

60. Standard documented system for

  • Specification
  • Sampling
  • Testing and
  • Release of materials and products

61. Testing

  • Physical
  • Chemical
  • Microbiological/ Biological

62. Tolerance of Electronic balances.

63. Testing of Validation Batch/Scale Up batch Record.

64. Temperature and Relative Humidity Monitoring Record of Oven Humidity chambers.

65. TLC qualifications are document keeping.

66. Validated Excel Sheet for Calculation.

66. Working standards & reference standards.

  • Maintenance
  • Documentation
  • Listing

1. Air Sampling plan of Specific Area .

2. Autoclave validation Record.

3. Autoclave operational Record.

4. Bacterial Endotoxin Test[BET], Sterility Test, Environmental Monitoring Test failure investigation report.

5. Calibration records of equipment’s.

6. Calibration & Recording keeping of Micropipette.

7. Calibration records of measuring devices.

8. Calibration record for heating block for BET.

9. Disposal of microorganism, used culture media, used plates etc.

10. Environmental monitoring records.

11. Growth promotion records of media.

12. Environmental Monitoring and Water Analysis Record.

13. Filter integrity tests record for filters of LAF.

14. Incubators calibration Record.

15. LAF Validation schedule.

16. Microbial culture management.

  • Name of the organisms
  • ATCC/NCTC numbers
  • Sub-culturing of organisms
  • Preservation of microbial culture

17. Master list of SOPs, specifications & methods are updated.

18. Operational Logbooks .

19. Preventive Maintenance schedule for LAF filter cleaning.

20. Record Keeping for Bacterial Endotoxin Test[BET] and Sterility Test.

21. Stock stains available.

22. Testing area.

  • Adequacy of space
  • Adequacy of equipment
  • Cleanliness

23. SOP for

  • Gowning and De-Gowning Procedure Though the Change Room of Microbiology Area
  • Management of Water Sampling and Testing
  • Microbial Disposal of Waste Media
  • Operation of Colony Counter for Microbiology
  • Cleaning and Sanitation of Microbiology Laboratory
  • Operation and Maintenance of Single Door Autoclave
  • Operation, Calibration and Maintenance of Laminar Air Flow Cabinet
  • Operation and Maintenance of Bacterial Incubator
  • Operation and Cleaning Procedure of Oven
  • Preparation and Preservation of Microbiological Media

24. Temperature charts and records of BOD incubators

25. Validation of autoclave machine

26. Validation of LAF

27. Validation Record of BET kit

28. Water monitoring records

This is all about the Audit Checklist [Internal Audit/Self Inspection Checklist] for Quality Control Department [QC & Microbiology Lab] [but not limited to]

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Powder and Granules, what do you mean by Powder and Granules?

Powder and Granules: here is the brief description of Powder and Granules, You will get the short description of Powder and Granules in this area-

Definition of Powder

Powders, which are finely divided solids, offer versatility in industry and everyday life through easy integration with solvents such as water, facilitating a variety of applications such as pharmaceutical formulations and industrial processes, while being tailored to specific needs and requirements. can be adjusted. This improves human health, comfort and productivity.

Powder, often understood as a finely divided solid substance, has many uses in industry and everyday life. Its versatility lies in the fact that it is easily mixed with suitable solvents such as water or liquids, making it easy to apply in a variety of forms and functions. For example, imagine a powdered drug, a common scenario in the pharmaceutical industry. This powdered drug can be dissolved in a suitable solvent, such as water, to form an orally administrable solution. Alternatively, the powder can be applied topically and used as a powder to treat skin conditions or wounds.


Additionally, the composition of the powder can be made individually depending on each need. Diluents are often added to pharmaceuticals to adjust the density and properties of the powder. For example, liquids contain small amounts of methyl paraben and propyl paraben, typically in a 2 to 3:1 ratio, which is about 0.05% to 0.10% of the total mixture. This combination is classified by the FDA as “generally recognized as safe” (GRAS) for food preservation, ensuring both effectiveness and safety of the final product.


The classification of powders goes beyond their composition to include a variety of uses. For example, powders can be classified according to their use, such as pharmaceutical powders for medical use, cosmetic powders for beauty products, and industrial powders for manufacturing processes. Each classification may have specific requirements and regulations that apply to production and use.

In essence, the definition of Powder goes beyond a simple physical state and embodies a realm of possibility where careful composition and application can lead to innovations that improve human health, comfort, and productivity.

 

Classification of Powder on the basis of use.
  • Internal Use Bulk Powder
  • External Use Bulk Powder
  • Unit dose or Divided Dose Powder
Internal Use Bulk Powder

The finely divided chemicals or drugs in dry form can be used in internal purpose [Oral Power]

Classifications:

  • Dry powder inhalers
  • Effervescent powders
  • Oral powder
  • Powder spray
External Use Bulk Powder

The finely divided chemicals or drugs in dry form can be used in External purpose [Dusting Powder] and available in multiple doses[Dusting Powder]

Classification:

  • Dentifrices
  • Dusting powders
  • Insufflations
Unit dose or Divided Dose Powder

The finely divided chemicals or drugs in dry form can be used in internal purpose [Oral Power] but the individual doses are separately wrapped.

Classification

  • Powder for injection
  • Effervescent powders
  • Douche powders
Classification of Powders based on size

Powder can be divided into several categories based on its size.

  • Macroscopic Powder
  • Microscopic Powder
  • Submicron Powder
  • Nano Powder
  • Ultrafine Powder

Macroscopic Powder:

These powders have particle sizes ranging from 10 μm (micrometers) to 1000 μm. They are usually visible to the naked eye and are often used in applications where physical properties are important, such as tablet or granule production.

Microscopic Powder:

The particle size of this powder varies from 0.1μm to 10μm. They are invisible to the naked eye and are widely used in pharmaceutical, cosmetics and other industries where fine particles are needed for specific properties.

Submicron Powder:

The particle size of this powder is 0.01μm to 0.1μm. They are very fine and are used in advanced materials, nanotechnology and some medical applications where precise control of particle size is essential.

Nano powder:

This powder has a particle size of less than 100 nanometers (0.1 μm). They exhibit unique properties due to their small size and high surface-to-volume ratio and have applications in fields such as electronics, catalysis, and drug delivery.

Ultrafine Powder:

These powders have particle sizes ranging from 1μm to 100μm, which are finer than macroscopic powders but larger than fine and submicron powders. They are used in a variety of industries including paint, varnish and additive industries.

Classifying powders based on size is important because it affects the properties, behavior, and uses of the powder. Different particle sizes can lead to changes in fluidity, compressibility, surface area and reactivity, among other things. Therefore, understanding and controlling particle size distribution is important in many industries to achieve desired performance and effectiveness.

Mixing of Powders

The use of double tapping technology is essential for accurate mixing of powder ingredients, especially in pharmaceutical manufacturing where precise dosing is important. Known in the pharmaceutical industry for the efficiency of geometric dilution, this technique ensures uniform distribution of ingredients in the mixture.

The process begins with carefully measuring the smallest powdered substances and placing them in a mortar. Then more powder is added to the mortar in equal amounts. After mixing the two ingredients, rub the mixture vigorously until you have a uniform mixture. This rigorous mixing process ensures that each particle of the small ingredient is distributed evenly into the larger mass, preventing potential concentration gradients or uneven dosing.

One of the key principles of geometric dilution is the concept of incremental addition. As the mixing process progresses, each time you add more powder, you actually double the amount of material in the mortar. This incremental concentration ensures consistency and uniformity of the final product by ensuring small ingredients are fully incorporated into the overall mixture.

A practical example of the application of this technology is the development of effective drugs, especially those containing hormonal components. These preparations require precise doses of the active ingredient, which is usually present in small quantities. By using geometric liquids via double tapping technology, pharmaceutical manufacturers can ensure that these powerful compounds are evenly distributed throughout the formulation, reducing the risk of dosage variation and ensuring the safety and efficacy of the final product.

 

Process Steps

To facilitate homogenization and to prevent stratification the particle size has to be reduced. The process steps is depicted here-

  • Sieving
  • Weighing of each ingredient
  • Mixing
  • Packaging
General method for preparation of bulk Powders: Geometric dilution
  • Firstly weigh the Smallest Volume[Powder X] and place into a mortar
  • Secondly weigh the Large Volume[Powder Y] and place into a separate labeled container
  • Add the same amount of Powder Y as of same amount of Powder X into the mortar
  • Use pestle to mix well
  • Now add the same amount of “Powder Y” as the same amount of Powder as of Mortar then mix with Pestle, continue this process. Every time the powder quantity will be double compare to previous quantity in mortar.
General method for preparation of Divided Powders
  • Weigh the Active ingredients and diluent accurately.
  • Arrange trituration of two powers separately before mixing.
  • The mix the two ingredients with spatulation method.
  • Place the powders in a surface ensure they are in proper quantity using block and divide method.
  • Arrange dividing the quantity as per requirement.
  • Wrap them into individual paper.
  • Place them into individual container and
  • Finally label the container.

To dilute the active ingredients of the powder, generally lactose is used to produce the required quantity due to Lactose is colorless, odorless, soluble and also harmless can easily maintain the flow property. The patient who are susceptible to Lactose then Light Kaolin may be used.

Powder calculations

If you are dealing with Powder calculation, you have to calculate at least 1% extra powder to compensate loss during compounding.Always try to take minimum quantity of active ingredients compare to dilution, then minimum weighable quantity is diluted several times.

Advantages of Powders
  • Powder is more stable compare to liquid dosage form
  • Very much useful for multiple dosage of single product
  • Helpful for children and senior citizen
  • Ensure first rate of bioavailability due to small particle size
Disadvantages of Powders
  • Unstable in atmospheric conditions
  • Uniformity dosage failure occur frequently
  • Not suitable for carry out from here and there.
Shelf life and storage of Internal Powders
  • Internal powders shelf life is 14 to 30 days
  • Due to protective packaging proprietary power have longer shelf life
  • Powder should be store in moisture proof and airtight area.
Shelf life and storage of External Powders
  • External powders shelf life is 30 days.
  • If ensure proper packaging then dry power remain stable in longer period of time.
  • Must be store in a cool and dry place.
Containers for Internal Powders
  • If powders are prepare extemporaneously then then wrapped powders are often dispensed in paperboard box.
  • An air tight container is preferable to store internal powder to protect from moisture.
  • Almost all bulk powders are packed in airtight container.
Containers for External Powders

Glass, metal or plastic containers can be used for storage of external powders. For packaging of propellant and lubricants, pressurized containers are commercially available to ensure proper safety and security.

Labels and advice for Internal Powders

Mix with suitable solvent or supplied solvent if comes with powder container itself otherwise mix indicated amount of water slowly in a divided portion and shake upon addition of divided amount. Don’t add all indicated amount of solvent at a time. Add it gradually in several portion. Bulk powder must be dilute and measure carefully. Bulk powder use for babies can be placed into mouth with a drink

Labels and advice for External Powders
  • For external use only.
  • Store in cool and dry place.
  • Protect from direct sunlight
Uses of Powders
  • The powder is uses for the following cases-
  • Used as counter-irritant e.g camphor starch dusting powder.
  • Used as antimicrobial e.g. Chlorhexidine dusting powder.
  • Used as antipyretic e.g. ipecacuanha and opium[Dover’s Powder]
  • Treatment of antacid and anti-flatulent e.g. Magnesium trisilicate
  • Used as antiseptics i. g. 5% of Povidone-Iodine Powder[Betadine Powder]
  • Treatment of juvenile arthritis i.e. Ibuprofen powder
  • Aluminium free baking powder e.g. Rumford
  • Widely use in Cosmetics and Face Powders
  • To relief skin burn e.g. prickly heat powders
  • Protect skin and nappy rashes e.g. Baby powders
  • Used in dyspepsia e.g. Rhubarb powder

 

Granules:

Granules are produced by the agglomeration of minute particle produce large free flowing particles. The particle range vary between 4 and 10 mesh size. Most of them are irregular shape but need to produce spherical shape. Granules are the intermediate form of Tablets and Capsules.

What’s the advantage of Granules over Powder?
  • To avoid powder separation.
  • To increase the flow of powder.
  • To increase higher porosity.
  • To increase the compressibility of powder.
  • The materials having lightly hygroscopic tendency may adhere and form cake if store in powder form.
Classification of Granules

Granules are classified into following Categories

  • Coated granules
  • Effervescent granules
  • Gastro-resistant granules
  • Modified release granules
Coated Granules

The granules are undergone single or multilayer coating process with the help of various types of excipient form coated granules use in multi dose preparations. The materials which are used to coat the granules are firstly made solutions or suspensions with suitable solvent may be Organic[Isopropyl Alcohol/Methanol/Metethelene Chloride or Inorganic[Water]. Solvents are generally evaporate during coating process.

Effervescent Granules

The uncoated granules, generally contains acid substances and hydrogen carbonate or carbonate which react instantly with water upon addition with it and release carbon-dioxide. The granules must be dispersed or dissolved with water before administration.

Gastro resistant Granules

The granules that are intended to resist the gastric fluid and release the active ingredients in intestinal fluid well known as delayed release granules. The gastro resistant properties are just attain by coating of suitable materials[Polymer Like-Hydroxypropyl methylcellulose phthalate/vinyl acetate phthalate/Cellulose acetate trimellitate/esters of aleurtic acid/Cellulose acetate phthalate etc.]

Modified release Granules

The granules contains special type of excipients or that is prepared with special procedure are both involved, and designed to altered the rate, the place or time at which the active ingredient release. The modified release granules are two types as Delayed release granules and Prolonged release granules.

Granules preparation Methods

All of the granules are made of mainly in two method

  • Dry Granulation Method
  • Wet Granulation Method
Dry Granulation Method

Dry Granulation methods are performed in two ways-

  • Roller Compactor
  • Slugging
Roller Compactor:

The dry powder passed through roller compactor then a granulating machine. A Roller compactor is also familiar as roll press, roll compactor use to process fine powder to dense sheet form by forcefully passing through two heavy rotating metal roll running counter to each other.

To attain different forms and textures the surface of the compacting rolls may contain corrugations or pocket indentation and surface of roller compactor may be smooth to do the same. The compacted powder further granulated in a mechanical granulator to get uniform particle.

Slugging

During slugging process the pressure may be difference between 8,000 to 12,000 lb to form large tablets based on the physical characteristics of powder form. The produced slug may be in flat faced in 1 inch diameter.

The resulted slugs are granulated to produce desired particle size used to produce tablets and capsule. During dry granulation, some fine particles are produced that is not agglomerated, the fines particle are collected, separated finally reprocessed.

 Wet Granulation Method

In the wet granulation method the, paste prepared by moisten the powder or powder mixture then the paste passed through the specific screen of mesh size and produced desired size of granules. Granules are then placed on tray for drying and dried it by heat or air. The granules are periodically moves on the drying tray to avoid adhesion to outsized mass.

The other type of wet granulation method is known as fluid bed granulation processing (also known as agglomeration) where particles are placed on conical shape of equipment and liquid excipient spray on the particle in  vigorously dispersed and suspended conditions then the product dried to form pellets of defined granules size.

How to prepare Effervescent Granules?

Here two methods followed-

  • Fusion method
  • Wet Granulation method
Fusion Method

The method, where equivalent molecule of Water and Citric Acid present[One Molecule of water in each molecule of Citric Acid] act as binding agent for Powder. First of all the Citric Acid Crystals are made powder then this powder mixed with other powder. Same sieve size to be ensure to get uniform powder mixture. The mixing equipment’s and the sieves are made of stainless steel to avoid effect of the acid

To avoid premature chemical reaction and absorption of moisture the mixing of powder performed rapidly in a low humidity area. Then the powder mixer transfer a suitable dish in an oven which temperature between 34°C to 40°C. Use heat resistant spatula to turn the powder. During this process, the heat release water of crystallization from Citric Acid which dissolve a portion of this power mixture and initiate chemical reaction produce Carbon Dioxide cause the soften of powder mass. Then the powder become to extend spongy and this spongy powder then rubbed through a sieve to produce desired size granules.

Various size of sieves are available in the market produce different size of granules e.g. No. 4 sieves use to produce large granules, No. 8 sieves use to produce medium size granules and No. 10 sieves use to produce small granules. To get best result during storage the granules are dried below 54°C and rapidly placed in container just after drying and tightly sealed.

Wet Granulation Method:

The wet granulation method is different  from that of the fusion granulation method as water didn’t come from crystal stage of materials and additionally water to be added moisten the granules. Here all materials remains anhydrous until addition of water. After addition of water the prepared mass are then dried to prepare desired granules.

Shelf life and storage:

The Shelf life of the granules is 2-3 weeks. Granules should be stored in double layer polybag in airtight containers, add silica gel pouch outside the container to get proper result. Must be stored in cool and dry place and protect from direct sunlight.

In this way Powder and Granules are very essential to our day to day life. Powder and granules are consider the important part of pharmaceutical preparations. Special precaution may requires during manufacturing of powder and granules. This is all about the short brief description about Powder and Granules. 

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Difference between Powder and Granules in Pharmaceuticals Industry?

Difference between Powder and Granules, Definition of Granules:

Difference between Powder and Granules, Granules: It is the aggregations of small particle of power varies in size between 0.2 and 0.4 mm depending on their subsequent size. When granules are used as Tablet and Capsules, their size may vary from 0.2 and 0.5 mm.

They are generally spherical in shape but size may be change based on varies size reduction process. In pharmaceutical industry, the powdered particles are combined to form bigger one is known as granules which is used I various pharmaceutical compounding.

Powder:

Difference between Powder and Granules, Powder: The power can be defined as a dry bulk solid composed of fine particles and free flowing on shaken or slanted. This is the special type of granules but the term granules and powder used to distinct different type of materials. Actually powder means very fine particle and granules means larger coarse particle. Powder refers to the finer particle compare to granules.

Due to particle size variation powder shows lower flow property and the granules shows the higher flow property. Due to small particle size the power easily form clumps when start flowing and granules generally tend to form clumps, only when we wet the granules then it form clumps.

Importance of Powders and Granules in Pharmaceutical Sector

 

The particle form granules then the segregation of granules tend to less compare to power. The granules can easily withstand in atmosphere upon standing in long time but powder can’t stand long tine in this condition. You can wet the granules in more easy way by liquid solvent. Various types of dry powder products are available in the current market which further made solution and suspension upon addition solvent. Generally powder in pharmaceuticals company considered in solid dosage form which may contains medicinal or non-medicinal [Excipients] ingredients use for external or internal purpose. The pharmaceutical powder may be obtained from comminuting, grinding and crushing. The particle size of the powder may vary from 10 nm to 1000 μm.

In the modern history the usage of powder is increasing day by day in various field mainly in chemicals, cosmetics, foods and pharmaceuticals. The most of the pharmaceuticals dosage form administer as solid stage dosage form which is mainly prepared by powder [Granules] by means of various ways as processing and formulations.

The widely used pharmaceuticals dosage form is tablets and capsule. The usage of powder has been replaced by the widely used pharmaceuticals dosage form, Tablets and Capsule. That is the most traditional form of medicine continue to use this dosage form until today and continuing.

 

Difference between Powder and Granules?

Powder Granules
Any distinct/discrete particles having size less than 1000 µm is known as Powder.Aggregations of small particle of power varies in size between 0.2 and 0.4 mm known as Granules.
Having higher cohesive strength due to fine particle.Having lower cohesive strength due to coarse particle.
Flow property is very low compare to granules and not suitable for tablet compression.High flow property compare to Powder can produce uniform tablet weight.
During compression this can be separated if it contains different ingredients.Less chance of separation during compression though it contains different ingredients.
Due to high cohesive strength, it forms high density layer at the upper portion create weight variation during compression. Due to low cohesive strength, it forms uniform layer in every portion produce less weight variation during compression.
Air may entrapped during compression of tablets increase capping tendency.Less chance of air entrapping during compression so significantly reduce capping tendency.
It may be blown from the die and cause frequently sticking problem during tablet compression.It can’t blown out from the die so less chance to cause sticking problem during compression.
The Flow-Function[FF] value is lower limit, so it shows low flow property on hopper.The Flow-Function[FF] value is higher limit, so it shows high flow property on hopper ensure smooth operation
It requires steeper hopper angle to ensure flow property.Not require to steeper hopper angle, work well in any suitable hopper.
Not suitable for compression tablet, Encapsulation process, may be used for dry solid preparation which further tend to form solution and suspension upon addition of solvent.Very much suitable to compress tablet and Encapsulation process, produce uniform tablet and Capsule

Advantages and Disadvantages of Pharmaceutical Powders

Advantage of Powders

Pharmaceutical powders offer numerous benefits to the pharmaceutical industry.

  • Ease of administration: Powders can be formulated into various dosage forms such as tablets, capsules, suspensions or solutions, making them versatile for oral, topical or inhalation administration.
  • Better solubility: Some drugs are poorly soluble in liquid form but can be soluble in powder form, increasing bioavailability and therapeutic efficacy.
  • Dosage flexibility: The powder allows precise dosage control and allows the dosage to be adjusted according to the patient’s needs. This is particularly useful in pediatrics and geriatrics where dosage adjustments may be necessary.
  • Stability: Many pharmaceutical powders are more stable than liquid formulations because they are less susceptible to chemical degradation or microbial contamination.
  • Longer Shelf Life: Properly manufactured and stored powders have a longer shelf life than liquid formulations, reducing the frequency of production and replenishment.
  • Easier to transport and store: Powders are often lighter and more compact than liquid formulations, making transport and storage easier and less expensive, which can be particularly useful in resource-limited environments.
  • Flexibility in formulation: Pharmaceutical powders provide flexibility in formulation development by mixing various excipients to modify release kinetics, improve taste, increase stability or facilitate administration.
  • Reduced risk of spills and leaks: Unlike liquid formulations, powders are less likely to leak or leak during transport and handling, reducing waste and potential safety hazards.
  • Customization: Powder formulations can be customized for patients with specific requirements such as: B. Patients who are allergic to certain ingredients or who require special dosage forms such as powders for reconstitution.
  • Cost-effectiveness: In some cases, manufacturing pharmaceutical powders can be more cost-effective than manufacturing liquid formulations because the manufacturing process is simpler and packaging requirements are less.
  • Pharmaceutical powders are the preferred dosage form for many drugs in the pharmaceutical industry as they offer numerous advantages in terms of delivery, stability, flexibility and cost-effectiveness.

 

Disadvantages of Powders

Like any other drug, pharmaceutical powder also has its drawbacks. Some of these are:

  • Limited comfort: Powders often need to be measured and mixed with water or other liquid before ingestion, which can be particularly uncomfortable for patients with mobility or dexterity issues.
  • Dosage Accuracy: Ensuring an accurate dosage can be difficult with powders as slight differences in measuring or mixing can result in inaccurate dosage delivery.
  • Stability: Some pharmaceutical powders may have stability issues, especially if they are sensitive to humidity, air, or temperature. This may affect its lifespan and performance.
  • Palatability: Many pharmaceutical powders have an unpleasant taste or texture, making them difficult for patients to swallow or ingest.
  • Storage: Powders may require specific storage conditions to maintain stability and potency, such as: B. Cool, dry environment or protected from light.
  • Dosage Flexibility: Powders do not offer the same level of dosing flexibility as other dosage forms, such as tablets or capsules, which may limit their usefulness in certain situations.
  • Accidental inhalation: There is a risk of accidental inhalation when handling powders, which can be particularly dangerous for some medications.
  • Manufacturing Challenges: Manufacturing pharmaceutical powders can be complex and require specialized equipment and processes, which can increase manufacturing costs.
  • Packaging: Powders may require special packaging to ensure proper control and dosing, which can increase production costs and have environmental impacts.
  • Patient Compliance: Some patients may have difficulty adhering to the regimen of measuring and mixing powders, resulting in medication compliance issues.
  • Powdered pharmaceuticals can be effective for drug delivery, but they also have some disadvantages that must be carefully considered when choosing the appropriate dosage form for a patient.

 

 

Advantage of Granules

Pharmaceutical granules offer many advantages over other dosage forms such as tablets or capsules. These benefits include:

  • Enhanced solubility: Granules can be designed to increase the solubility of poorly soluble drugs, thereby improving absorption and bioavailability.
  • Dosage uniformity: The use of granules allows better control of dosage uniformity, ensuring consistent dosing for patients.
  • Taste masking: Granules can be coated or formulated to mask unpleasant tastes or odors associated with some drugs to improve patient compliance, especially in children and adolescents.
  • Formulation Flexibility: Granules provide flexibility in formulation design, allowing the inclusion of multiple active ingredients, controlled release formulations, or combination treatments.
  • Stability: Granules can improve the stability of some drugs by protecting them from degradation due to environmental factors such as humidity, light, or oxidation.
  • Ease of administration: The granules can be conveniently administered by mixing them with food or liquid, making it suitable for patients who have difficulty swallowing tablets or capsules.
  • Reduced risk of underdosing: Granules allow the full dose of drug to be released quickly, reducing the risk of underdosing, which may cause side effects or treatment failure.
  • Customization: Granules can be customized to specific patient groups such as: b. Pediatric or geriatric patients can adjust the size, flavor, or properties of the formulation to suit their needs.
  • Improved dissolution rate: Granules with optimized particle size distribution can have a higher dissolution rate, resulting in faster onset of action and better therapeutic results.
  • Ease of production: Granules can be produced using a variety of techniques such as extrusion, spheronization or spray drying, allowing for scalable and cost-effective production.

Overall, pharmaceutical granules offer versatility, precision, and improved performance compared to other dosage forms, making them an attractive option for drug delivery in a variety of therapeutic areas.

 

Disadvantages of Granules

Like other pharmaceutical formulations, pharmaceutical granules have disadvantages. Here are some potential pitfalls:

  • Limited solubility: Some pharmaceutical granules may have limited solubility, which may affect absorption and bioavailability in the body. This may cause the potency and effectiveness of the drug to vary.
  • Uniformity Issues: It can be difficult to achieve uniform granule size, shape and distribution of the active ingredient, especially in large-scale production. Inconsistent dosing and effects may occur.
  • Stability issues: Granules are more prone to disintegration and instability than other dosage forms such as tablets or capsules. Factors such as humidity, temperature, and light exposure can affect the stability of active ingredients.
  • Difficulty in handling: Granules can be more difficult to handle than other dosage forms, especially in terms of packaging, transportation and administration. Handling and processing may require special equipment and skills.
  • Palatability: Some granules have an unpleasant taste or texture that may reduce palatability for patients, especially children or those who have difficulty swallowing. This may affect patient compliance and medication taking.
  • Dosage Flexibility: Granules may not offer the same level of dosing flexibility as other dosage forms, such as tablets or liquid formulations. Dosage adjustments may require reformulation or changes in manufacturing.
  • Cost: The development and production of pharmaceutical granules can be expensive, especially if special equipment and processes are required. These costs can be passed on to consumers, making drugs more expensive.
  • 8. Regulatory Issues: Regulatory approval for pharmaceutical granules may require additional data and documentation compared to traditional dosage forms. This may increase the time and resources we spend developing and marketing our products.
  • Environmental Impact: The production of pharmaceutical granules can generate waste and pollute the environment. This is especially true if solvents or other chemicals are used. Proper disposal and environmental management are important aspects.
  • Overall, pharmaceutical granules offer several advantages, such as improved bioavailability and dosing flexibility, but there are challenges and drawbacks that must be carefully considered during product development and use.

Difference between Powder and Granules in Pharmaceuticals Industry? Read More »

Frequently Asked Questions in VIVA and its Answer

Frequently Asked Questions in VIVA, Here are some questions which are asked almost all type of VIVA

Note: All questions-answers are depicted here, those questions answer are explanatory/descriptive and link is given here. Click the link, you will get the answer. Only Short answers are given here otherwise you have click the link for descriptive answer.

Q-01: Tell me about yourself?

Answer: When answering the typical “tell me about yourself” interview question, it’s important to write a compelling, concise description that highlights relevant skills, experience, and accomplishments. Here’s a structured way to write a response:

Introduction: Start with a brief overview of your professional background and current position. for example:
“Of course I would like to see my background. I have a bachelor’s degree in [your field] from [university] and have been working in [your industry/field] for [X years]. I am currently [your current position or role].”

Professional History: Highlight the milestones and experiences that have shaped your career. Focus on accomplishments that demonstrate your qualifications for the position you are applying for. Examples include:
“Throughout my career, I have had the opportunity [to mention notable achievements or roles]. For example, while previously working at [Company Name], I led the project [Describe a successful project or initiative]. [Specify relevant skills] This experience has allowed me to hone skills that will be invaluable in this role.”

Skills and Strengths: Discuss your key skills and strengths and highlight those that fit the job requirements. Provide specific examples to illustrate each point. for example:
“I’m just as good at [citing specific skills or strengths] as I am at [giving examples]. While working at [previous company], I was praised for my ability to [describe relevant skills or strengths], which led to [positive outcomes], such as B. increased efficiency or sales.”

Passion and Fit: Finally, express your enthusiasm for the opportunity and how your background aligns with the company’s mission or values. Show genuine interest in the position. Examples include:
“I really welcome the opportunity to [mention your passions or interests] and [mention specifics about the role or company]. I appreciate [company name]’s efforts to [state relevant values or initiatives], and my expertise in [your core competencies] will help you [state how you can contribute to the company’s goals] I believe this can be done. “

Conclusion: Ends the discussion with an open invitation to further discussion or questions.
“I’m excited to learn more about how I can contribute to [company name]. Do you have specific questions about my background or experience?”

Tailor your answer to the position you are applying for, keep it short, and focus on the most relevant information. Practice ahead of time to ensure your responses sound natural and confident during the interview.

 
Final Answer

“Of course I would like to see my background. I have a bachelor’s degree in [your field] from [university] and have been working in [your industry/field] for [X years]. I am currently [your current position or role].”

“Throughout my career, I have had the opportunity [to mention notable achievements or roles]. For example, while previously working at [Company Name], I led the project [Describe a successful project or initiative]. [Specify relevant skills] This experience has allowed me to hone skills that will be invaluable in this role.”

“I’m just as good at [citing specific skills or strengths] as I am at [giving examples]. While working at [previous company], I was praised for my ability to [describe relevant skills or strengths], which led to [positive outcomes], such as B. increased efficiency or sales.”

“I really welcome the opportunity to [mention your passions or interests] and [mention specifics about the role or company]. I appreciate [company name]’s efforts to [state relevant values or initiatives], and my expertise in [your core competencies] will help you [state how you can contribute to the company’s goals] I believe this can be done. “

“I’m excited to learn more about how I can contribute to [company name]. Do you have specific questions about my background or experience?”

 

Q-02: Why do you work with us?

Answer: I decided to work for you for several reasons. They all align with my professional ambitions and personal values. First, your reputation for innovation and excellence in [specific industry/sector] is very interesting. I want to contribute to a team that continues to push boundaries and set industry standards.

Second, I am very impressed by your company’s commitment to [specific values or initiatives such as sustainability, diversity, community involvement, etc.]. I believe in aligning my personal values with those of the organization I work for and welcome the opportunity to contribute to meaningful initiatives that have a positive impact on the company and the wider community.

Additionally, I am truly impressed by the quality of your team and the collaborative culture that has been fostered here. I look forward to learning and working with talented people because I believe that collaboration and teamwork are essential success factors for any company.

Overall, I think working with your company is a personal and professional development opportunity. Here I can offer my skills and expertise and learn and develop in a dynamic and supportive environment. “I’m excited to join your team and contribute to your continued success and innovation.

Q-03: What is your strength?

Answer: When asked what my strengths were, I emphasized my adaptability and ability to learn quickly. Throughout my career, I have faced a variety of challenges and tasks that have required me to quickly understand new concepts, techniques, or methods. This adaptability has allowed me to thrive in a fast-paced environment and contribute effectively to diverse teams. Additionally, I believe that excellent communication skills allow me to communicate complex ideas effectively and collaborate with colleagues to enhance my abilities in any role. Overall, I think adaptability and communication skills are my biggest strengths. This allows you to tackle any project or problem with confidence and competence.

Q-04: What is your weakness?

Answer: As I progressed in my career, I realized that I tended to be overly critical of my work. This has led me to strive for excellence and continually strive for improvement, but I’ve also learned that it’s important to balance that with acknowledging my accomplishments and being kind to myself. To solve this problem, I started implementing strategies like setting specific goals and objectives, asking for feedback from others, and celebrating successes along the way. Not only has it helped me perform my role more efficiently, but it has also helped me maintain a healthy work-life balance.”

This response acknowledges weaknesses (without being overly critical) by highlighting the steps taken to address them and demonstrating the candidate’s commitment to personal growth and development. It also emphasizes positive traits such as confidence, resilience, and a proactive approach to self-improvement.

Q-05: Why we should hire you?

Answer: “I believe my combination of skills, experience and passion will make me the perfect person for this role and a valuable addition to your team. I have honed my skills in [a specific skill or specialty] with [X years/months] of experience in [your field/industry].

What sets me apart is my proven track record [mention notable accomplishments or accomplishments relevant to the position]. I am also adaptable and thrive in fast-paced environments, as evidenced by my ability to lead by example in successfully managing challenging situations or projects.

Additionally, I am truly excited for the opportunity to contribute to the mission and goals of [company name]. I am committed to bringing my unique perspective and innovative ideas and collaborating with my colleagues to drive success and exceed expectations.

Overall, I am confident that my skills, experience and passion make me the ideal candidate for this position and I welcome the opportunity to contribute to the continued growth and success of [company name].”

This answer effectively highlights your qualifications, accomplishments, and passion for the position and demonstrates why you are the best person for the job.

 

Q-06: What do you know about our company?

Answer: “Prior to this interview, I did a lot of research about your company and was really impressed with what I learned. You continue to enjoy a reputation for innovation and excellence in [specify specific industry or specialty]. Setting a new standard. I was particularly attracted to [specify relevant aspects such as technology, sustainability or community] because of the impact of your recent [specify specific project, product or initiative] and also [specify relevant aspects such as technology, sustainability or community]. “I see your commitment to [or the principles the company emphasizes, such as diversity and inclusion, environmental sustainability, and customer satisfaction] that align perfectly with my professional values and have a huge impact on the organization.”

 
Q-07: Why do you want to leave your current company?

Answer: When asked why I want to leave my current company, I see this as an opportunity to highlight what I’m looking for in my career rather than just focusing on what I want to leave behind. Although I have enjoyed my time at my current company and the experience I have gained there, I believe now is the right time to explore new opportunities that are more aligned with my long-term career goals and aspirations. I am looking for a role that offers greater challenge, opportunities for growth, and greater alignment with my professional values and interests. After careful consideration, I have concluded that this position is the ideal next step for me. This allows me to further develop my skills and make a meaningful contribution to teams and organizations that share my vision for success.

Q-8: What is your salary expectation?

Answer: When asked about my salary expectations, I respond by expressing my willingness to negotiate a salary that is fair and reflects the value I bring to the job and the organization. I understand that compensation is determined by a variety of factors, including the responsibilities of the position, company budget, and industry standards.

Ideally, I’m looking for a compensation package that matches my skills, experience, and market price for similar positions. Can you tell me more about the salary range for this position or the typical compensation structure within your company? This will help you better understand the parameters and reach a mutually beneficial agreement.

Q-9: What is your career objective?

Answer: “My career goals are to continue to grow and develop in my field and utilize my skills and experience to make meaningful contributions to the organizations I work for. In the short term, I want to excel and master the role I am applying for.” Create responsibilities and add value where possible. Looking to the future, I seek to take on more responsibility and eventually reach a position where I lead a team. Strategic initiatives “I can lead and drive and have a positive impact on the growth and success of the company. Ultimately, my goal is to continually learn, innovate and contribute to both personal and organizational growth.”

Q-10: Why You are Interested in this Position?

Answer: “I am very passionate about [the position or some aspect of the company] and this role is a perfect fit for my skills, experience and career goals. I’ve been following your company for a while and have been impressed by your commitment to [mention company-specific values, innovations, or achievements].

I also think this position is an exciting opportunity to [state specific goals or challenges associated with the role], which is incredibly motivating. I thrive in an environment where I can use [benchmark-related skills or strengths] to make a meaningful impact, and I believe this role does just that.

Additionally, I am very excited about your company’s growth potential and learning opportunities. It is important to develop yourself professionally while passing on professional knowledge. Overall, I am very excited about the prospect of joining your team and contributing to the continued success and innovation of [company/sector/industry].”

This response demonstrates passion for the job, alignment with company values and goals, and a focus on personal and professional growth within the position. This is all about the Frequently Asked Questions in VIVA.

Frequently Asked Questions in VIVA and its Answer Read More »

CV of a Officer, Quality Assurance, Standard Format

CV of a Quality Assurance Pharmacist

Isabella Paris

House No.: 7, Road No.: 7, Block : L

Email:[email protected]

Career Objective

Currently I’m looking for an opportunity to utilize my attained skills and working out to assist the company to achieve goal and my future career advancement. I want my hard work to make a substantial difference to the company and help in their subsequent success stories.

Experience

Now I’m working as Officer Quality Assurance at XYZ Pharmaceuticals Ltd from May 20xx to till now.

[Omit this section, if you are Fresh employee]

Key job responsibility

In-process control

BMR/BPR issuance

Batch Compilation

Sampling of Products

[Omit this section, if you are Fresh employee]

Education Qualification

Master of Pharmacy [Mpharm]

Institution: ABC University

Duration: 20xx to 20xy

Result: 3.50 out of 4.0

Bachelor of Pharmacy [Bpharm]

Institution: ABC University

Duration: 20xx to 20xy

Result: 3.80 out of 4.0

Higher Secondary Certificate

Institution: ABC College

Year: 20xx

Group: Science

Result: 4.80 out of 5.00

Board: DEF

 Secondary School Certificate

Institution: ABC High School

Year: 20xx

Group: Science

Result: 5.00 out of 5.00

Board: DEF

In-plant Training

I have completed my internship training in ABC Pharmaceuticals limited for four weeks in the year of 20xx.

Project work

I have submitted my project report on “Evaluation of analgesic, neuropharmacological and cytotoxic activity of Trigonella foenum-graecum Linn” presented to the department of the pharmacy at UOK under the supervision of Dr. XY Petersen professor, UOK.

Computer skill

Microsoft Office Suite

Basic Computer Skill

Internet Surfing

Basic Hardware Maintenance of Desktop PC

Adobe Graphic Suite

Language Skill

Have proficiency in English and French both in writing and reading

Personal Information

Father Name: Peter Francis McGrath

Mother name: Cristina Paris

Date of birth: 19xx

Gender: Female

 Reference

1. Professor HC Peter

Faculty Head, UOK

2. Professor YK Demes

Head of Pharmacy Department, UOK

I, hereby, declare that each of the information cited above is true and any intentionally made mistake will result me in disqualification.

Isabella Paris

CV of a Officer, Quality Assurance, Standard Format Read More »

Write down an application for the post of Officer, Quality Assurance

 

Application for the post of Officer, Quality Assurance, you can follow the following template for the mentioned post-

28th May 20XX

To

Manager

Human Resource & Development

ABC Pharmaceuticals Ltd.

121, Lakeshore Area, XYZ-700001

Subject: An application for the position Officer, Quality Assurance

I would like to express my interest and qualifications after seeing the job posting for the position of Quality Control Manager at your famous pharmaceutical company posted on xyz.com.

Throughout my career, I have consistently demonstrated a commitment to superior quality management through timeliness, dedication, integrity, effective team-building skills and a strong professional attitude.

For example, while working at [previous company], I led a project to optimize the quality control process, which resulted in a 20% improvement in product reliability and customer satisfaction. This initiative demonstrated not only my attention to detail, but also my ability to work with cross-functional teams to achieve organizational goals.

Please see attached resume and current color photo. If you have any questions or would like to schedule an interview, please feel free to contact me at 01XXXXXXXXX02. I welcome the opportunity to contribute to your team and am confident that I can excel in the role of QA Manager.

Sincerely Yours

Isabella Paris

 

Application for the post of Officer, Quality Assurance: That is the basic format.

Write down an application for the post of Officer, Quality Assurance Read More »

Why Are You Interested in this Position? Interview Question

“Why are you interested in this position?” Frequently asked questions during interviews often surprise job seekers. However, this is an important question that reveals your motivation and passion for the job. Let’s dig deeper and use real-life examples to explain why this question is asked and how to answer it honestly, positively, and effectively.

Employers ask this question to determine whether your interest in the job is genuine and whether your skills and aspirations match the position. Imagine a scenario where you apply for a marketing manager position at a technology startup. The interviewer wants to understand why you are attracted to the position and how you believe you will contribute to the growth of the company.

To write a compelling response, it’s important to tailor it to your specific role and company. Start by expressing your genuine interest in the position and mention things like the company’s innovative marketing approach or its goals for disrupting the industry. For example, mention your passion for using new technologies to run targeted marketing campaigns that align with your company’s forward-thinking ethos.

Next, highlight the unique skills and experience you have and look for similarities between the responsibilities of your current role and your desired position. Let’s say you are currently a digital marketing specialist at a traditional advertising agency. You may also express a desire to move into a leadership role where you can drive a comprehensive marketing strategy while leveraging data analytics and campaign optimization skills.

Additionally, demonstrate your willingness to take on new challenges and make a significant contribution to the role. Share past projects or success stories that demonstrate your ability to innovate and achieve results. Perhaps you’ve led a cross-functional team to launch a successful social media campaign that significantly increased brand awareness and engagement metrics.

Ultimately, your answer should convey a genuine passion for the role and a clear idea of how you can contribute to the company’s success. By aligning your interests with the job requirements and expressing your value proposition effectively, you can make a lasting impression on the interviewer and increase your chances of getting the job.

The application format may vary depending on the employer, but the basic goal is the same: to assess motivation and suitability for the job. Approach each interview with preparation and authenticity, personalizing your answers to highlight your strengths and fit the role.

 

  • Why you like our company?
  • What part of the job role you like most?
  • Are you interested to take the new role?
  • Why you are interested to take the new role?
  • Which part of the job is interesting to you?
  • Tell us why you are interested this position?

All of those questions contains the same answer. Now, we will discuss how we can prepare the best answer for this question” Why are you interested in this position?

 

“Why are you interested in this job?” Why employer ask this question?

As part of the employment evaluation process, employers often ask leading questions with the intention of broadly assessing several important aspects to comprehensively determine a candidate’s suitability for a particular role. This multi-faceted test will give you an idea of the complexity of the position, your true passion for the role, your possession of the required knowledge and experience, and your potential positive impact on the overall success of the company.

Imagine a scenario taking place in a dynamic software development company that carefully selects candidates for project management roles. In this context, interviewers look for a candidate’s deep knowledge of the software development lifecycle and assess his or her familiarity with agile methodologies and related tools. To capture genuine engagement and interest, conversations strategically include emotional questions and highlight trends in team collaboration and innovation.

An essential part of this evaluation process is reviewing the candidate’s performance. Particular emphasis will be placed on previous experience successfully managing projects and competently handling problem-solving situations. This historical perspective allows interviewers to assess a candidate’s suitability based on practical knowledge and skills acquired over time. As the interview progresses, discussions will explore the candidate’s strategic vision and ability to lead the company toward tangible, positive results, including increased productivity, improved customer satisfaction, and timely completion of projects.

Essentially, employers are looking for candidates who not only meet the company’s immediate needs but also demonstrate a proactive attitude toward ongoing personal and professional development. Valuation is not just a transaction. This extends to those who actively contribute to the company’s success and continually look for opportunities to develop further. This symbiotic relationship between individuals and organizations develops further when candidates actively contribute to the company’s success and pursue opportunities for continuous improvement. This collaborative approach promotes a win-win dynamic and creates an environment where both the organization and its employees can develop and grow together.

“Why are you interested in this role?” How to prepare answer?

We have to maintain some steps to create the best answer for this positions. Follow the descriptive points, we will prepare a best answer-  

Collect information about the company

First of all read the job description carefully and surf the internet to collect the basic information about the company. Almost all company have a website, where you will get the all information that you want. Basically learn their business standard, mission vision, working environment, employee facility, product and service but not so much deep.

If you can express your know how at the interview session for the company, surely you will get better preferences at the interview session. The interviewer will show the positive response to you, they will start thinking that you are interested to play the new role.

Organize your answer and try to memorize the keyword

When you complete the research about the company then you can start your answer preparation considering several points-Is this role is relevant to your experience? Is it help your career advancement process? What is the most unique point of this job? Organize your answer one step another then you can step forward.

Add a question at the end of the interview

When you think that the interview are about to end the try to ask a question to the interviewer about the most relevant topic to the job description this will create a two way facility that you are more interested to the job and the interviewer will think about you that you are very much interested about the role. Try to avoid any unnecessary questions. It will be better to keep silence without bother the interviewer by your immature questions.

Following are some example about “Why are you interested in this position”

Quality Control Manager

For over 10 years I have been committed to contributing to the success of my current employer, where I find great satisfaction in my role as a manager and leading a team of 20 employees. The experience I have gained over the past 12 years has been invaluable in shaping me into a professional ready to take on new challenges and greater responsibilities.

After receiving your latest newsletter, I am very excited to be taking on a leadership position leading a team of over 50 employees. This opportunity fits perfectly with my professional development ambitions and allows me to leverage my extensive leadership experience to have a greater impact on the organization.

As I look forward to transitioning into this new role, I am interested in understanding the different types of teams within an organization and the specific managers associated with them. Gaining insight into the dynamics and responsibilities of these teams will undoubtedly enhance your effective leadership abilities and contribute significantly to the overall success of your organization.

You may use specific examples from your current position to illustrate your preparation for this role. Over the years, I have led teams that successfully launch innovative projects, resulting in measurable improvements in productivity and overall team morale. This experience not only improved my leadership skills, but also gave me a solid foundation to tackle the complexities of leading large teams.

Lastly, I am excited about the prospect of leading a team of 50+ people. I am committed to understanding the different team structures and each supervisor. This knowledge will enable you to accurately lead and contribute meaningfully to the continued success of our organization.

Quality control Analyst

In my current role, I actively contribute as a team player and work collaboratively to get work done. However, opportunities for professional development and role expansion are limited in your current position. After reviewing your latest circular, it has become clear that the open position fits my ambitions perfectly and provides an ideal platform to expand my professional skills by working with cross-functional team members.

For example, in my current role, I have successfully collaborated with colleagues on multiple projects, demonstrating my ability to work well in a team. Despite my commitment to teamwork, I would like to have a broader role where I can work on a variety of projects and interact with professionals from different departments. The advertised position not only reflects my skills, but also promises an environment that fosters cross-departmental collaboration and leverages existing skills while acquiring new ones.

Given my passion for my future role, I would like to know how your company creates an environment that supports employee engagement. Can you provide information about opportunities and initiatives to ensure employees, especially those working in cross-functional teams, feel valued and supported in their professional development within the organization?

Why Are You Interested in this Position? Interview Question Read More »

What Makes You Unique? How to give best feedback at interview

What Makes You Unique ? the way to get a new job is obviously to submit an application to the respective organization to their mailing address by email or offline mailing system like FedEx or various courier service but the more interesting thing is that thousands of same qualified employee applied for a single position. Do you really have any chance to get the job? Simply the answer is NO.

Yes, you can’t expect the job if you didn’t possess anything that will be unique from others. Why interviewer choose you? You are so smart or you are very good to look at, that’s are personal belonging not fit to get a job actually. You have to meet the job criteria actually.

A person with typical qualification is hard to fight with the other job seeker if he didn’t possess extra thing. What is this extra thing? In this session we are going to learn about this extra thing!

When thousands of employee apply for the same post this is very natural that your qualification will overlap with other job seeker and this time you have to find out which criteria you possess that fit with the applied job makes you unique from others.

In the interview session, the interviewer may ask you the familiar question “What make you unique?” Take this opportunity, give your answer in more specific way with full confident and accurate result. Be honest at your answer so interviewer can trust you and they can realize that you are really bring some the benefit for their organization. So let’s go, how we can make this question answer.

what make you more unique

“What makes you unique? “Why frequently interviewer ask this question

The very first reason is to ask this question is, the interviewer just want to identify the employee who is the best fit for the role compare to other candidate they are interviewing. This can be simply say that why you not others where nearly all of the candidate possess the same qualifications.

Secondly the interviewer want to know that how you are evaluating yourself. They can realize that which thing you are emphasize at your interview session. If you able to emphasize the point that the interviewer really asking for the role then you can go with it. The employer want strong mentality but basic skill person which may not include with your application.

How to prepare you for the question

I think this is very difficult to identify anything which is really make you different from the other candidate. So let it go, prepare with your experience, focus on your strength which can increase your strength. Explain how interviewer will be benefited to hire you. Use your relevant background which is best match for the job. You can express your specific background that is really relate with this job.

Realize the interviewer asking about the positions

All of the interviewer always like the employee who will possess right skill set, perspective, ability to achieve target at every situations. So take time and think that are you really fit for the job. Read the job description completely, if you get any keyword then that is the best match for you then prepare yourself with that questions which point the interviewer may find effective if you properly deliver it.

Focus on your previous achievement

In professional life, you may be experienced with so many unwanted situations and bring back it normal. Some problem may be more challenges and some are not. Note the point where you face more challenges and how you overcome that. Relate this similar problem that me helpful in interview session.

You present those example where you were the key person no other colleague. Professional experience where your involvement was minor doesn’t require to mention in interview session, this will prove that you are unable to handle the situation.

Deliver the specific type of example which is more relevant with your work, try to create it more realistic rather than descriptive.

For example, “You are able to handle customer complaint and recently you have receive an interesting complaint and you have solve this issue and create a new facility/process/method to do the same. You can share this experience here”

Expression may be, ”Two month ago, I received a complaint about one of our new product that the customer received empty blister contains one tablet less out of ten tablets in a blister. I investigate the matter and find out that the pocket of all blister is same except one. During automatic filling process one tablet can to be filled due to small size of the pocket. Then we change the pocket size questing the supplier and include weight checking after blistering process. Now we are not receiving this type of complaint anymore”.

Highlight your most popular criteria

Try to mention your more strength point which your previous employees are appreciated and you can apply the same here will facilitate your job role. You can express “How other people know your patience and dedication to your professional life and how you face the hard situation in high stress situation, also mention your dedication during unfavorable condition”.

Never try to show your unique experience

Every employers are searching for the best for the best not a person contains unnecessary skill which is not relevant with the job description. Try to avoid the unnecessary skills which will bother the interviewer.

For example, “If you are applying for a position for Warehouse Officer, the interview panel is not interested that your good at website design and development, this is totally your personal matters not relevant to your applied position”.

Here is some example “Tell us what makes you unique”

“To organize & labelling something will save the time and space is my moto in the professional life. After joining of the current office as Quality Assurance Officer in document section, I made a list of our document as per product category in alphabetic manner at excel tracker with proper labelling has decrease the hassle during tracking of the product. It has been save our time and organized our working environment”

“My ability to make easy and smooth communication to my peer’s colleague and rapport building with them make me more unique in my professional life. As Admin Officer, I start a WhatsApp group and start connecting to the relevant colleague who are looking for quick admin support regarding transport and emergency hospital support. I want to spread my service and profession will help the others who are really feels their demand to be filled up quickly. I can easily identify the pain points of the employee and their challenge to acquire it”.

Every employee contains some inner traits that he can’t realize properly what makes him unique. If he able to identify the criteria and properly deliver it at the interview session will bring a better result for the employee.

 

Criteria of effective feedback

When it comes to providing effective feedback during an interview, there are several key principles that, if followed, can significantly improve the quality and impact of the feedback provided. Let’s take a closer look at the individual principles and expand on them using real-world examples.

  • Explain in detail
  • Focus on behavior
  • Balance positive and negative
  • Provide constructive criticism
  • Encourage self-reflection
  • Maintain professionalism and empathy
  • Follow-up
 
Explain in detail:

Instead of giving general comments, drill down into the details by providing specific examples and observations. For example, instead of saying that the presentation lacks depth, you could provide simple feedback such as “The presentation lacks data to support the financial projections, making it difficult for the audience to understand the feasibility of the strategy.”

 

Focus on behavior:

It is essential to focus on feedback on observable behavior rather than judgments about individual characteristics. For example, instead of accusing someone of being “disorganized,” you might say, “During a project meeting, you failed to set a clear agenda and assign tasks, causing confusion among team members.”

 

Balance positive and negative:

While it is important to address areas needing improvement, it is equally important to identify strengths and successes. For example, interview responses can not only point out areas for improvement, but also praise the candidate’s strong communication skills and insightful approach to problem solving.

 
Provide constructive criticism:

Feedback should not only highlight areas needing growth, but also provide actionable suggestions for improvement. For example, if you are criticizing a candidate for answering a difficult question, you can express your constructive criticism by suggesting specific strategies to improve the answer, such as: b. Include relevant examples or improve your presentation.

 
Encourage self-reflection:

Encouraging respondents to reflect on their feedback promotes a culture of continuous learning and improvement. For example, after providing feedback on a candidate’s performance in a mock negotiation exercise, you might ask the candidate to reflect on his or her approach and consider how he or she might apply his or her strategies in a similar situation in the future.

 

Maintain professionalism and empathy:

Feedback should be provided in a way that maintains professionalism and empathizes with the feelings of the interviewee. For example, when providing feedback to assess a candidate’s technical skills, you can provide constructive criticism in a polite tone without undermining the other person’s confidence or discouraging further effort.

 
Follow-up:

Following up with respondents after a feedback session demonstrates their commitment to growth and development. For example, after providing feedback on a candidate’s mock presentation, you might suggest scheduling a follow-up session to clarify any outstanding questions or provide further guidance on areas needing improvement.

By diligently adhering to these principles, interviewers can provide feedback that is not only valuable and constructive, but also helpful to the interviewee’s professional development.

What Makes You Unique? How to give best feedback at interview Read More »

Make a Great Impression on Interview, How to Proceed?

Make a great impression on interview, this session may divided into three sections

  • Before starting interview session    
  • At interview session
  • When you just complete your interview session
Before starting interview session       

The very last day before seating your interview session, you have to arrange some time to do the same which will help you better to understand your situation.

  • Start Researching about the company
  • Start Practicing with common interview question
  • Get prepare according interviewer job Description
  • Follow PDCA cycle to answer the question
  • Execution of Plan
  • Collect appropriate references
  • Prepare with real life professional experience
  • Be proactive not reactive
Start Researching about the company

Make a great impression on interview, Now a days any established company possess a well-designed website contains all basic information regarding company mission, vision, target, goal, achievement, CSR[Corporate Social Responsibility], product and service list, Top management profile and overall summary of the company. Most of the company contains Social Media Profile, Page, and Group etc. You can start your research regarding the respected from here.

From the Facebook group and page, you will find the information regarding company culture, employee activities, management policy, press release etc. even you can find an old friend who are working in the company if you are like enough.

Start Practicing with common interview question

Tell me about yourself is the most common interview question, this question may arise different form like express yourself/Can you please tell your career goal/Summarize yourself/ Present yourself/Give me basic information about you/How can you express yourself and the answer same.

Another interview question is Why you choose our company/Why you leave your current company/Why we should hire you/ Give me some reason that you are the best of all/What is your salary expectation/Why you asking more salary/What is the negative side of your company?

 You have to prepare align with the common interview questions. Hope this will help you during interview session.

Get prepare according interviewer job Description

Read carefully the complete job descriptions and qualification, job locations and related information so that the best result you can get. Mark the keyword of the job descriptions and match with your existing criteria if you are go well with that or not. Please don’t apply the job position which didn’t match with your criteria to avoid any unwanted occurrences during interview session.

 You may want to print it out and begin underlining specific skills the employer is looking for. Think about examples from your past and current work that align with these requirements.

Follow PDCA cycle to answer the question

Make a great impression on interview, You have to use PDCA cycle to answer the questions. You have to exercise PDCA [Plan, Do, Check, Action] to answer the question. Plan your interview session, take necessary measure to execute the plan, Seek any error present or not, if found correct the error, then finally execute your plan.

Execution of Plan 

After making a list of common interview question and necessary answer then you can engage your close friend as interviewer and start practice with questions and answer. More and more practice will increase your capability to deliver the answer. After a certain period of time your confidence will high and you will get the best result from this action.

Collect appropriate references

Before or after your interview, the interviewer musk ask you list of reference. So it will be the wise practice to collect list of referees before start the main interview session. This approach will also help you to facilitate the hiring process.

Prepare with real life professional experience

Make a great impression on interview, exercise with your best professional experience where you played major role and solve the issue with excellent solution. Deliver the answer if ask “What is best work of your professional life and how you solve that issue”. You can prepare your answer with your professional experience or volunteer works which praise more.

Be proactive not reactive

Today interviewers are very much smart, they just not only like to questions to the employee but also expect questions from employee. Create a list a smart questions bank is essential smart interview session. In the very past it was the common thinking that to ask question to the interviewer is a serious crime but today the scenario has been changed, the road has just change from one way.

make great impression on interview

Be sure what you are asking to the employer the approach at smart way-

  • Can you please explain the job description of this post?
  • Can you share a success store who has been a successful leader in the similar role?
  • How you will evaluate my position?
  • Have any opportunity to migrate cross functional department?
  • How I will get confirmation to my position?
  • Is this position allow team work or I have to standalone?
  • Who will assist me to perform the day to day activities?
At interview session

Make a great impression on interview, on the interview day you have to proceed your next activity as follows-

  • Be aware to prepare your dress code
  • Be aware about Interview accessories
  • Time planning to reach interview location
  • Make positive first impression
  • Keep your respect on everyone
  • Time to show you manner
  • Ready to show your positive attitude
  • Keep silence and avoid any unnecessary airy gesture
  • Use professional achieves with every answer
  • Give your feedback in short and concise 
Be aware to prepare your dress code

If possible ask the interviewer for your dress code. Some of the company also mention their dress code via email and some are not. You can ask contact person about this issues. You can search internet about this issue” How to dress up for a formal interview?’’ Normally a black pant with white full shirt with neck tie and leather shoe was the trend in the past but most of the employee break the tradition wearing colorful full sleeve shirt, pant etc. A better looking spectacles can easily help to increase your personality.

Be aware about Interview accessories

Make it simple, just bring your recent resume, pen, PP size color photo, small notebook, ID card, highlighter and please avoid your smart gadget, you can bring smartphone but you have to keep it vibration otherwise keep it silent for the best. Try to maintain polite eye contact with the interviewer as much as possible.

Time planning to reach interview location

You can use google map to estimate the time to reach the spot of interview. It is the best practice to reach the location at least 30 minutes earlier. If you don’t know the location of the interview, feel free to contact with the contact person of the interviewer “How can you reach their location effetely, try to use personal transport or ride sharing service, avoid public transport for better preparation. If you use public transport, you must have a backup plan if traffic jam or closure or special occurrence.

Make positive first impression

Time to shine up your tiny expression- just make nails and teeth are clean enough, your cloths are stains, hole and extra thread free and lastly shine your favorite shoes. Show strong and confident body language that you are ready to take any challenge and keep your smile face during interview.

Keep your respect on everyone

On the interview location treat everyone with great respect. You should respect everyone security person to hiring manager, you didn’t know is actually hiring manager, plant manager and Quality head and so on. So keep your respect on.

Time to show you manner

Before enter into the interview room, ask permission to enter the room. Before the interview take a deep breathe to bring confident to you and avoid any negative fillings. When the interviewer extend their hand you have to firstly look their eye create a gentle smile and initiate handshake with them. A soft handshake is always preferable.

Ready to show your positive attitude

Nothing can, only attitude can win everybody heart. Deliver your most positive and specific answer what the ask not some much details. The interviewer must be beat you with series of questions to show their existence. You have to remain upbeat for a time being during interview session. Showing a positive answer with light smile face is always create a healthy interview environment.

Keep silence and avoid any unnecessary airy gesture

Keep at steady position and avoid any unnecessary body language, just focus on interviewer question, what he is asking to you? If you can’t hear or read the answer ask a repeat question politely ”Sorry, I can’t read you, can you please repeat the question”. If don’t know the answer of the asked questions, politely say” Sorry, I don’t know the answer of the questions exactly, can you please ask another question”

Use professional achieves with every answer

Try to answer any question with your practical professional’s achievements. If you can attach example with every answer then the interviewer will start to believe that you are the only one person who can solve their problem. Relate your answer with their requirements as per job descriptions.

Give your feedback in short and concise

Remember, your time in the interview session is very limited, so you have to answer in short and concise but informative and affirmative. Make your descriptive answer in short, only highlight on your answer keyword.

Keep your present job in positive side

Try to give your negative answer in positive way. Never underestimate or under value your current organization. Remember, no company like the negative person only want the problem solver not problem creator. Generally, company hire the employee when they face the tough situation to run their business.

Most of your answer must be consist of professional experience or something related with that but not personal comfort. Keep your eyes open if you receive any email or SMS or WhatsApp text. Generally you will get the result within one week to one month.

When you just complete your interview session

Make a great impression on interview, at the end of your interview, try to ask your hiring manager for the next steps. Most of the company inform by email for positive or negative result. Some of the company don’t send any rejection SMS or email or WhatsApp only inform if your selected for the next round.

Final communications                            

Never forget to collect ask business card from each interviewer for to send thank you email personally. If you face interview in morning session you have to send your email in evening and for other session send your thank you email in the next day but not to exceed 24 hours.

The content of the email must short and distinctive. Don’t send group email. You must be send the thank you mail separately. Generally all of the top management involve in interview session and they didn’t like group email at all from a job seeker. In this way you can make a great impression during interview session.

 

Factor affecting Great Impression on Interview

Making a compelling and lasting impression in an interview requires a careful mix of preparation, good communication skills, and solid professionalism. We dive deeper into preparation and explore a wide range of strategies, illustrated with real-world examples, that can significantly increase your chances of success.

  • Thorough company research
  • Introduction to resume
  • Common key interview questions
  • Workwear
  • Punctuality
  • Body language
  • Active listening
  • Express your passion
  • Thoughtful questions
  • Focus on soft skills
  • Post-interview follow-up

Thorough company research:

Learn about the company’s ethos, cultural differences, and overall mission. For example, if you’re applying to a technology company that promises innovation, demonstrate your ability to adapt to cutting-edge tools or methods. Understand the role and complexities of the sector. If you want to take on a marketing position at a fashion company, understanding the latest trends and market dynamics is essential.

 

Introduction to resume:

Prepare a brief discussion of the experiences, skills, and achievements described in your resume. For example, if you’ve worked on a successful project, be prepared to explain the challenges and accomplishments. Highlighting specific accomplishments that directly match the job requirements highlights your skills. If you are applying for a leadership position, discuss how your leadership has dramatically improved team performance.

 

Common key interview questions:

Guess and practice your answers to the most frequently asked interview questions. Using the STAR method, share a scenario where your innovative thinking led to a positive outcome. Tailoring responds to the specific requirements of the job. For example, if you’re applying for a customer service position, highlight an example of how you overcame a difficult situation with your problem-solving skills.

 

Workwear:

Choose attire that reflects the company culture and the position you are applying for. While a well-tailored suit may be appropriate in a corporate environment, a versatile style is desirable in creative industries. Your choice of clothing should reflect your understanding of your work environment. A graphic designer position may allow you to be creative, while a finance position may require a more conservative approach.

 

Punctuality:

Arrive on time to demonstrate your commitment to punctuality. This not only reflects your interest, but also provides margin in case of unexpected delays. Imagine a situation where a candidate arrives early due to an unexpected traffic jam. This proactive approach speaks volumes about their commitment.

 

Body language:

Demonstrate confident body language through consistent eye contact, a firm handshake, and upright posture. This can be described as a candidate who conveys confidence and approachability through body language, which are key characteristics for customer-facing roles. Using subtle body language, such as nodding your head in agreement or leaning forward slightly, can emphasize your participation in the conversation.

 

Active listening:

Demonstrate active listening by carefully answering the interviewer’s questions. An example would be a candidate who, when asked a complex question, takes time to organize his or her thoughts before giving a comprehensive answer. Avoiding interruptions and asking for clarification when necessary shows your commitment to clear communication.

 

Express your passion:

Express your genuine passion for the company and the position. When applying to a startup, explain how your passion for innovation perfectly matches the company’s ethos. Connecting your personal career goals with your business development can create a compelling story.

 

Thoughtful questions:

Prepare probing questions that explore business dynamics, team cohesion, and role complexities. An example of this would be a candidate trying to understand employee development or the company’s future vision during an interview. A thoughtful request shows your genuine interest and strategic thinking.

 

Focus on soft skills:

Emphasizes the importance of soft skills such as adaptability, teamwork, and effective communication. Share an example of how team spirit contributed to project success. In today’s dynamic workplace, employers value candidates who can integrate seamlessly into diverse teams.

 

Post-interview follow-up:

Send a personalized thank you email within 24 hours. Express your gratitude for the opportunity and reiterate your enthusiasm for the position. To enhance engagement, focus on specific aspects of the interview. A timely and thoughtful follow-up not only highlights your professionalism, but also ensures that you remain the center of the interviewer’s attention.

Simply put, excelling at interviews requires a holistic approach that goes beyond simple competencies. Integrating these skills with real-world examples not only increases your chances of success, but also sets you apart as a fully prepared and engaged candidate who is strategically aligned with your company’s vision and values.

Make a Great Impression on Interview, How to Proceed? Read More »

Why do you want to leave your current job, how to explain?

Why do you want to leave your current job, this is the very common question by the interviewer during interview session. The HR manager/Hiring Manager always interested to know the actual reason to leave your current job so that they can collect more information about ability, integrity, working capacity, your importance to the current job. Also justify your problem solving capacity in an undesired situation.

So before leave a current job and to face a new interview session you have to face different type of questions which answer must be previously prepared. Take some time to prepare yourself. Try to prepare a logical, reliable answer so that the interviewer can rely on your answer and believe it with full confident then he can take positive decision about you.

You can answer the question” Why do you want to leave your current job?” in various ways but remember it “Interviewer will not suggest the Hiring Manager to hire you until he is satisfied your positive response”. Here is depicted some season which you can corporate at your structural answer-

  • You are not properly evaluated
  • You want more compensation package
  • The existence of the company is going to invalid
  • You are undervalued at your current position
  • You are ready to take new challenge
  • You want a job with better future career plan
  • You want a job with new opportunity to enhance next level of career
  • You are leaving your existing job due to family matters
  • You are unable to suite you current office time schedule
  • You are going to leave current city
  • You want to reactivate your career
  • Decided to go back to your university for new course
  • You are not fit for current company culture
  • You want a better career opportunity
  • You want to change environment for doctor’s decision
  • You want work with the market leader
  • You want to work in different company
  • You want to change your existing position
  • You want next level promotion
  • Your current company is unable to give any remuneration package
  • Your company is going to change its business criteria
Be clear about your reasons for exiting

Must be straight forward to give reason to leave your current company:

Most of the time employee fail to give the actual reason to leave the existing company. Take some time, make a list with positive reason to leave your current company. If you are hard to understand then you can go with the following reason. This can help to find out a common reason to leave your current company-

  • What is the aim of your career?
  • Are you satisfied with you career?
  • What you want to be?
  • What really you want and what you received?
  • What do you want after 5 or 10 years?
  • What you want the new job?
  • Why you like new job role?
  • Are you undervalued?
  • Why you don’t like your current job?
  • Are you fail to make positive rapport with your colleague?
  • Are your manager not satisfied with your activities?
  • What is your relation with peer colleagues?
  • Which type of industry you really like?
  • What is real mission and vision?
  • Are you want to be an entrepreneur?
  • Why you are not satisfied with your current job?
  • Are you really dissatisfied with your current job role?
  • Are you in faulty situation?

Write down the some key reason to change your existing job. Try to select more professional reason not person. Try to be profession in terms of reason to leave job. Generally interviewer will not show any interest with your personal reason.

It is very desirable that you are going to leave your job for professional reason. Suppose your family is going to change the city and you want to leave your job. This is not a valid reason to interviewer for leaving your job.

why do you leave your current job
Describe your answer in a short session

It is very much important to keep your answer in short but you have to answer in full throttle and this answer may not exceed 45 sec. covered by two to three sentences. Then you have to point back why you are the best fit for the job.

Always stay positive mode

The reason of leaving current job may be in many reason most of them are person and financial matters. Employee engage in a job can’t move to another if he didn’t fall in less mental or job satisfaction. Nobody to leave his comfort zone even best performer of the year. A negative situation compel the employee to leave his current position. In job interview you can’t express the negative situation as”My reporting Manager is very rude to me. His behavior is not up to the mark, always pinch me badly. I fell always humiliated compare to others. Please save me…”

You have to be always in positive mode. You can’t express the negative situation to interview board though you are in false position. An interviewer never want a problem creating person, always seek problem solver. They are fond of a person who can work in stress condition or able to handle difficult situation.

You have to focus on your job expertise, what you have learn in the previous day and what you have to done to achieve your dream job. You know yourself very well not others, so try to develop yourself by discussing with others or taking any type training or surfing internet.

Try to increase interaction with your peer colleague, share your problem and try to find a positive response from others. Call an expert from your colleague who can solve your problem. Help your peer colleague and they will also help if a proper rapport build with them.

You can express your positive answer in interview session as”my current job role is very interesting and generally help to other colleague who is unable to realize their job role. Basically I perform the quality surveillance type job. I have learned various type of new skill by this way. Under this circumstances I am looking for a new role where I can apply my experience…”

Try to be authentic without being too comprehensive

When you are in this situation, try to explain your position positively, never hide any basic information. If you are not satisfied with your current job, there are hundred ways to share your information without defame your company? Keep your answer in short and focus on your new job opportunity that you are very much excited to get the job.

If you’re sacked or you are being compelled for some instances, express it positive way what actually happen. If you are not in on job. Tell it to the employer, don’t hide it. Employer always search your previous history. Without collecting any previous job history you will not able to get any job as experienced professional.

If employer found any provided information mismatch with your supplied answer, then you will not eligible for the job. Employer will no longer trust your position. You are probably lose this opportunity.

How to surround your explanations for leaving a job?

I think you have already listed your explanations to leave your current job. Here I am presented some explanations which may not properly presented on interview session. There is some explanation you may like to prepare your better explanation “Why do you want to leave your current job”

I don’t like my company

No company is errorless, there is a positive and negative side in each and every company. Take few minutes and think why you don’t like your company? Take this point and make it your target point and prepare the positive, clear, straightforward, precise and responsive answer based on this point.

For example:

Presently I am working with a renowned company with strong mission and vision. In the very recent time this is become very clear to me that I need more motivation from a stronger mission oriented firm. The mission of your company “Create possibility for underrated profession” attract me very much to work with and continue my positive career growth.

I have been working more than seven years and fond of to work with more communication and collaboration where the area of my work expansion is very much limited. I like a wide working environment where I can show my professional experience more broadly and continue my professionalism. I am very much excited to do the same.

More target more pay

This may be a great factor to leave your current position but this issue is more sensitive to share which can indifferently interviewer can interpret. Best option is to interact with more target oriented job, more possibility to get rewarded.

I am motivated with lot of factors, client satisfaction, peers satisfaction, excellent working environment, friendly reporting manager may be the top of the list but I like to receive more compensation package which is also a great motivation for me and I am very much excited to get the opportunity, want to exceed my target and get more rewards which drive me positively

“I am no longer like my job”

This condition arise from a situation where employee involve in long term monotonous job. Same day same position, no promotion, no motivation create a dissatisfaction to the current role. Opposite situation may arise, employee himself is not capable to play the current role, not like to take new challenge, fond of monotonous job. His skill and ability didn’t match with the current job.

Try to make a positive response based on which opportunity you are seeking and which challenge you want to take at your new role. “I have been working my current role more than three years and recently I am seeking more opportunities where I can continue developing my skill and abilities”

Or you can explain” I have gain more and more positive professional experience through my current job. Now I am searching more opportunity where I can expose myself as positive team leader and I am very much excited to do the same in my new role”

“I am unable to continue my office schedule”

Time management of a specific office play a vital role to do the activities. Almost every office follow the similar time frame in terms of General shift, Morning shift, Night Shift and another shift when require but not limited to. Perhaps you can involve in a different time frame office which totally different to standard system then you can go with this point to focus on as

”I know that I will perform very well when I am in healthy balance with work environment and positive time management. I am very much committed with my existing office schedule and all day I plan about this issue and I also like to take flexibility of time scheduling where applicable and continue my professional expertise in everyday life”

The very best expiation to leaving a job

There are many reasons you can and should explain why you’re looking for a new opportunity. As professionals grow in the workplace, there is a natural flow from one job to the next as people seek out new learning opportunities, career development, new environments and other factors. Let’s look at a few examples of good reasons you’re looking for a new job:

Searching for best career growth

Based on the company police, every company has its own style for career progression of the employee. Some company offer positive career growth with short period of time and others offer slow career progression. This the strong reason to leave the current job for positive career development. You can explain this situation in the following way.

I have been working with a positive minded co-worker and excellent working environment but no possibility to step forward to the next level. Your company mission and vision interested me for career advancement where I can able to show my own path based on performance based career progression”

Strong desire to change existing career paths

The very common thing is to people to explore the different career path in his lifespan. In his entry level of job, most the job seeker take offer of any type of job which may be justified with his educational qualification or not. Those who are not lucky enough take offer without any career planning. In some period of time or after few years they feel loneliness once meeting their old friends want change career path very desperately. Again they do the same wrong that was made at the start of their career.

Be cool and be simple. Think a while, are really want to change your career path? Is it require to change the existing position? Are you not happy enough with your post? It if yes then you can go with the answer during interview session.

I’m really looking for a new working space which is totally absent in my present organization where I can prove myself as a very good team leader and expand my real formulation skills of different pharmaceuticals area.

Identified a better chance

You have to leave your current company when you will get better opportunity, this may be your better salary structure, you will get extra benefits, better working environments, more evaluation of your work where you will show your better existence the you can go with-

“My job role was multidimensional and I have learned most of the critical assessment of risk. My actual goal was to save the company from any potential financial risk. I like to expand my expertise in cross-functional department but my existing position didn’t allow me to do the same”

Compel to go or laid off

This is the fate of some people which can’t avoid, don’t worry take some time and think a while and prepare a best answer why you are looking for the job. Try to avoid personal matters. You can take the following issue-

Be honest without describe any unnecessary details

Never mention the word” You are fired”

Explain the best you get from the situation

Give the reason why you are best fit for the available position

Here are the two options for the two different situations:

If you are compel to go:         

“I myself realize my previous employer and I realize my former employer and I had done some activities different way which was beyond their expectation. Now I have learn a lot and I’m very much excited about the role to bring that adulthood to my next professional life.

Your company is laid off:

“I am the sufferer by my current company, unfortunately is going laid off and 50% of the current employee is going to compulsory separation. For this unavoidable circumstances I like to move another destination before final separation where I can reshuffle my career and show my expertise”.

This is the all out the reason to “Why do you want to leave your current job? Hope this is all the issue but not limited to. There may be other severe reason when a person is compel to search a new opportunity.

Why do you want to leave your current job, how to explain? Read More »

Why are you leaving your current job? Interview question.

Why are you quitting your current job?” After an interview, the first question is often “Tell me about yourself.” This is an important question and one that is often asked by experienced professionals. This is an opportunity for candidates to build their story and leave a lasting impression during the interview. However, the answers to this question vary widely, and many professionals express dissatisfaction with their current work situation.

Imagine a scenario where a marketing manager is asked this question during an interview. They may respond by highlighting issues such as limited growth opportunities, mismatched company culture, or an unsupportive work environment. While these claims may be true, emphasizing them may create a negative impression of the candidate in the eyes of the interviewer.

In today’s competitive job market, interviewers are becoming smarter. They’re not just filling a position, they’re evaluating candidates for fit and potential contribution to the company culture. Therefore, negative reactions to one’s current job may not lead to positive outcomes for the job seeker.

Instead, candidates are advised to proceed with caution and provide more nuanced answers. Instead of obsessing over the downsides of your current job, you can focus on the opportunities you can find in your future role. For example, a marketing manager may emphasize a desire for a more collaborative work environment, professional development opportunities, or alignment with the company’s values and mission.

By reframing the narrative in a positive light, candidates can demonstrate insight and passion for new challenges. This approach not only demonstrates their expertise, but also leaves a positive impression on the interview group.

Ultimately, employers are looking for candidates who demonstrate optimism, resilience, and a solution-oriented mindset. While it’s important to recognize why you’re leaving your current job, highlighting your positive aspirations and goals for the future is also important to making a lasting impression in an interview. After all, no organization wants to hire someone with a negative attitude or past dissatisfaction.

Why are you leaving your current job

Leaving your current job can occur for a variety of legitimate reasons that reflect personal growth, professional ambitions, alignment with company goals, and more. Writing a positive and confident response to your reasons for leaving your current job not only shows confidence, but also emphasizes your commitment to finding someone who matches your skills and ambitions for your next position.

Why are you quitting your current job?” Consider these steps to effectively answer questions during an interview:

  • Emphasis on personal growth and development
  • Cultural Fit and Organizational Values
  • Professional Development and Learning Opportunities
  • Aligned with your long-term career goals

Emphasis on personal growth and development:

Emphasize how important your current role is to your career, but express your desire for new challenges and opportunities that will expand your skills. For example, explain how you have mastered your current responsibilities and are now seeking a role that will provide you with more leadership opportunities or allow you to delve deeper into a specific area of expertise. For example: “I really value learning and development opportunities in my current job, but I think I’ve reached a point where I’m interested in taking on more strategic responsibility and contributing to better connected projects.” My long-term career goals. I believe this new location offers just that.”

 

Cultural Fit and Organizational Values:

Discuss how you value cultural fit and seek out an environment where your values and work ethics align with the company’s values. Based on your research and conversations with current employees, you may like the culture of the new company and think it fits your work ethic better. Example: “I’ve had a positive experience at my current job, but I’ve realized that my values and work style are better aligned with your company. Their focus on innovation, collaboration, and talent development resonates with me and I’m excited about it.” We are contributing to that dynamic environment.” 

 

Professional Development and Learning Opportunities:

Express your desire for continued education and career advancement, and view your new role as an exciting growth opportunity. You can mention specific aspects of the new position that interest you, such as: B. Mentoring opportunities, professional development programs, or exposure to new technologies. For example: “I’ve had a lot of fun and learned a lot in my current job, but I believe this new role gives me the opportunity to further develop my skills and expertise [in a specific field]. I’m working on innovative projects and talent. With my colleagues.” The prospect of collaboration excites me and I look forward to contributing my experience as I continue to learn and develop professionally.”

 

Aligned with your long-term career goals:

Place your decision to leave the company in the context of your wider career and explain how the new role best suits your long-term goals. We will discuss how new business visions and developments provide greater opportunities for advancement and professional fulfillment. Example: “As I reflected on my career goals, I realized that this new role aligns with my long-term goals. The scope of [the specific opportunity or responsibility] fits my vision of where I want to be in the next few years.” “I’m very excited about the prospect of having an impact and growing the company.”

By using these techniques and providing clear, positive responses, you will show the interviewer your clear goals, commitment to growth, and passion for your future role, and will feel confident in your decision to pursue new opportunities and deliver your core values. can. What can you bring to your organization?

Focus on your expertise: “I have been reviewing and updating the all QMS related SOP’s and activities referencing the current cGMP guidelines of various regulatory bodies, I have been requested from our Head of Quality operations to update the existing QMS system with full throttle….”  

Keep it affirmative: “I am really looking for an opportunity where I can apply my full abilities of work to develop a complete QMS system with hundred percent cGMP compliance and I am very passionate to do the…”

Most of the cases, you have to face the unfavorable condition but you have to face it positively.

 

Narrate it back to the job: “I am very much excited to read the asked job responsibility along with job description which is to assessment of quality risk to existing brand product. This is such a great opportunity for me to develop myself in the area of quality risk management system…”

Why are you leaving your current job? Interview question. Read More »

“Tell me about yourself” what the best answer is?

Tell me about yourself, this seems very easy question to all. What is it, I can handle it very well? Really you can do that? Wait. It is not easy that you are thinking. This is really a Tricky question.

How to handle this question? Start with your background, Start with current status, start with future plan or you are going to answer it like a professional guy. I am sure you are just worried to give this answer. Well you are not the one. Thousands of job seekers are just waiting to get the best answer. Actually most of the people are tremendously struggle to do the same.

So how I get the best answer about the question” Tell me about yourself”

First, it’s important to understand why interviewers ask job applicants the question “Tell me about yourself.” From an employer’s perspective, this question serves several purposes. The goal is to obtain information about the candidate’s suitability for the position, personality, communication skills, and overall fit with the company culture. This is not about delving into personal or family history, nor about spreading rumors. Rather, it is a strategic inquiry aimed at understanding an individual’s nature.

Imagine a scenario where you apply for a marketing position at a tech startup. The interviewer may want to determine your marketing background, approach to problem solving, communication style, and your fit with the company’s culture of innovation. We want to gain insight into your professional identity to ensure that you have the necessary qualities and experience to excel in the role.

The answer to this question is very important because it sets the tone for the entire interview. This is your opportunity to create a compelling story that highlights your strengths, experience, and accomplishments as they relate to the position. Think of this as your elevator pitch. It is a short but effective outline of who you are professionally.

Imagine that you are the interviewer and you have decided to give a structured answer that highlights your experience with digital marketing, your passion for achieving results, and your ability to adapt to a rapidly changing environment. This answer not only answers the interviewer’s question, but it leaves a lasting impression and establishes you as a strong candidate for the job.

Conversely, imagine giving an unexpected or poorly worded answer that doesn’t meet your employer’s expectations. You may encounter irrelevant personal anecdotes or inconsistent descriptions of your background. In these situations, the interviewer may feel that you lack focus or qualifications for the position, which may cause them to question your candidacy.

Ultimately, the quality of your answer to the “Tell me about yourself” question can have a significant impact on how the interviewer views your suitability for the job. By writing thoughtful, relevant answers that reflect your qualifications and focus on the job, you increase your chances of advancing to the interview. It’s not about memorizing a script, it’s about conveying sincerity, professionalism, and passion for the opportunity given.

 

Give the answer at very much straightforward. A better answer must be-

Personalized- You are going to apply for a “Quality Control Job”. An employer didn’t want the production or Quality Assurance related experiences. Your answer must be relevant for the job that you applied for.

Well, it’s actually pretty straightforward. A good answer should be-

Specific on Experience– Please don’t say that “I am Isabela Paris and in the year of 20XX, I was High school student then in the year of 20XX I was College student then I myself admitted in the University of XYZ”. Your answer must be consist of your relevant experience, background, degree, achievements, your personal interest, hobby and current status.

Organized– You should follow the simply, smart, easy format so that everybody can easily read your speech very well. Never complex the simple issue. Try to keep it simple, just include the information what really you are. A typical answer may be consist of-

Present- Describe your current position, activities and major role

Past-Describe your previous activities, experience, achievements

Future-Describe your next plan that you are going to be that may be tell the interviewer that “Why you want this Job?

Here are some basic tips, you can follow the issue-

Be Professional in brief

When you are going to answer” Tell me about yourself”. Keep your speech not more than 2 minutes. No body want your entire life history at all even HR Manager. You can’t start with your Kindergarten / Primary School/ High School/ University Life or like that. Just deliver you specific point which is best fit for the job.

You can’t start with” I was a student of XYZ high school, since I grow up I passed my high school then I admitted myself at Higher Secondary School. After that I got myself admitted in University in the year of …

This is really a bad idea to do that, you have to start with your current status just like” Thank you very much for shortlisting me. I am Isabela Paris. I am Pharmacist with ten years of practical experience in different pharmaceutical company especially in document section both national and international affairs”. Just keep it simple.

Practice, practice and practice but don’t copycat others

In a modern interview session, you must hear “tell me about yourself”. So start practice this question. So how do you do that? Don’t worry. There is a better solution. Hire/request a friend to be your partner for a time being. Practice with that friend making him as HR Manager and you are the job seeker.

Remember don’t memorize the answer. Just took down the main point and practice with that. If you memorize then you are probably mess up in interview session while you forget it. Just create the idea and structure it as present, past and future and try to deliver it.

Remember, who is your audience?

 This is the vital point at the interview session. You have to know the member of the interview panel. Generally panel member introduce themselves, if not then you have to know them by the mode of their questions.

This is very important that who is talking with you and how you are handle with that. It may be your question, is it import? Well, there is an answer. Suppose you a Pharmacist and you are interviewing with HR manager. What then, you just start “I am a pharmacist, I know very well in powder technology and proper knowledge in dry granulation and wet granulation…? Is it perfect answer?

HR Manger didn’t know about powder technology nor dry granulation and wet granulation. A HR Manager generally known with more generic answer and your career, your applying reason, your expected salary etc. but when you interview with CEO or CTO then you can go with anything.

Structure your answer divided into different percentage

If you face the question “tell me about yourself” then you should remember the three Letter[WAP]-

Work-This section consist of more than 80% of the total answer

Academy-Consist of not more than 15%

Personal-This section generally minor and contains not more than 5% of the total answer.

Just after the greetings this the first question of the interviewer” Tell me about yourself”. In this session the interviewer really wants to know that what really you are. Just tell about your professional experience in this session, present, past and future plan. The interviewer want to justify the employer about their professional experience and next plan of the employee.

The employer want to know that the selected employee is fit for the asked position and do better for the same. Most of the employer generally want that the employee must be smart enough with current job descriptions and better know how about the designated position.

When you face the interview session and face this question “Tell me about yourself” then you should structure your answer in the following way-

A. For Fresh Graduates and College Student

Firstly, describe your current position/ situation/Status as likeMy name is Isabella Paris, I’m 23 Years of old and recently I have completed my graduation degree from University of XYZ with B.A. in Biotechnology and Genetic Engineering. I learned more about gene Biophysical Chemistry, Human Physiology, Enzymes and Enzyme Kinetics, Bioorganic Chemistry, Bioinformatics, GMOs and Biosafety, Bioprocess Technology, Genomics and Proteomics, Bioethics, Biostatistics and more. I was the part and parcel of the student assembly while maintaining GPA 3.7 out of 4”.

Secondly, try to summarize your previous experience with Achievement as like “During my study period I was voluntarily service our university library due to I love to know various types of subject related books rather than wasting time at to and fro. I was also involve in our university debate team and win two time championship”.

Thirdly, summarize your next plan, as like in this way I work hard to gain my knowledge from text book and other way, now I want to apply my knowledge through practice if I got any chance in your renowned organization. I have no practical experience but I have lot of coverage in real business environment.

I have completed lot of workshop which is related to real company problems. I am very much interested to deliver my all acquired knowledge in practical field and I think that I am the right person that you are looking for long time and best fit for the vacant position”.

Sample Answer for University Admissions:

B. Firstly, describe your current position/ situation/Status as like

” Hello, This is Isabela Paris, and I’m a elder at School of XYZ. I am almost better at my study plan and I am maintaining 3.8 GPA out of 4 though I am involve in various types of school projects and cultural activities. I am the chairman of “J.K Rowling Fantasy Club” which I started six month ago and continuing with more than hundred members as of now.

I am also the member of foreign student funding club and involve campus cleaning and hygiene program. We generally invite different university professor as guest lecturer for our campus cleaning and hygiene program”.

Secondly, try to summarize your previous experience with Achievement as like

“I am very fond of team work and never like to miss team building and try to continue the team spirit. I never hesitate to ask help from any one in any situation if I am unable to understand any subject matters. For instance, in the few month ago I was in trouble with “Algebra” which was little bit tricky for me then I ask help to my class teacher about this issue and request him to give me some extra time one after another day. At the end I got “A” in this subject”.

Thirdly, summarize your next plan, as like

Now at the University of XYZ, I’m preparing myself for major in Pharmacy or Molecular Biology. I also love to do lab work and study in a public library in the most of my leisure period”.

Sample Answer for Experienced Professionals

C. Firstly, describe your current position/ situation/Status as like

Yes, I am very much happy to do the same. Good Evening! Thank you for shortlisting me for the interview. My name is Isabela Paris. I am a Pharmacist with more than 10 years practical working experience in different pharmaceuticals company both in compliance and document section.

I am Master of Pharmacy and completed my graduation from XYZ University. Now I am involve in BPL as Assistant Manager, Quality Assurance. My major responsibility is to handle Change control, Deviation Management, CAPA, Quality Risk Management and product release.

Secondly, try to summarize your previous experience with Achievement as like

“In my previous organization I was involve in quality compliance section in more than 5 years where my major responsibility was In-process control of various pharmaceutical dosage form mainly in Tablet, Capsule, Liquid, SVP and LVP. There I was experienced with various types In-process control related Instruments especially in Disintegration Tester, Harness Tester, Electronic Balance, pH meter etc. with their qualification activities”.

Secondly, try to summarize your previous experience with Achievement as like

“before that, I was working as a project manager for Company Y that provided cloud computing solutions for about 6 years. There, I personally managed 5+ teams of software projects, and made sure everything went smoothly in terms of business goals, deadlines, budget, and more”.

Thirdly, summarize your next plan, as like

In my downtime, I enjoyed football and cricket also. This activity has shown me good strategy, consistency and determination can help to overcome any obstacle. I am person who thrives in a fast paced environment and right now I am looking for an opportunity to apply my practical expertise along with my creative problem solving capacity”.

“Tell me about yourself” what the best answer is? Read More »

Interview Tips in Pharmaceuticals and other Renowned Company

Interviews are the cornerstone of talent acquisition for pharmaceutical companies and are a critical time for human resources departments to carefully seek out people with the right skills and abilities needed for specific roles within the company. Imagine this. Our team of interviewers carefully evaluate candidates to find the perfect candidate who can handle the job requirements efficiently.

Imagine yourself in an interview room in front of a group of professionals tasked with determining whether you are a good fit for the company. This is your opportunity to shine, showcase your skills, and prove your value at the highest level of the company.

But more than just demonstrating your qualifications, the interview is a vetting process and an opportunity to convince the employer that you are the ideal candidate. The ability to effectively communicate your strengths, experience and aspirations is very important. For example, consider a scenario where two candidates have similar qualifications, but one of them demonstrates excellent communication skills and enthusiasm during the interview. Perhaps this candidate will make a strong impression and stand out as the preferred choice.

Consider the importance of body language. First impressions often set the tone for the entire interview. Your mannerisms, body language, and overall presence sometimes say more than your qualifications. People with a positive attitude exude confidence and charisma, traits that can overpower more experienced and unenthusiastic candidates.

It is important to maintain a positive attitude. Negativity breeds negativity, and employers are naturally attracted to candidates who exude optimism and resilience. Preparation is important. Being familiar with the company, the role, and potential interview questions will help you demonstrate your commitment and passion and help you stay ahead of the competition.

So as you prepare for your next interview, make sure you approach it with confidence and a positive attitude. Use these interview tips to leverage your strengths and present yourself as the best candidate for the job. Your attitude and preparation pave the way for success in your professional endeavors.

interview tips

 

List of Interview Tips
  • Leave an Unforgettable First Impression
  • Mastering Your Preparation for Success
  • Stand out by expressing your uniqueness and value proposition
  • Have a positive attitude to make a good impression on the interviewer
  • Master Body Language for Success
  • Stay calm even in difficult situations
  • Prepare for your interview with common questions

 

Leave an unforgettable first impression

The importance of making a good first impression during an interview cannot be overemphasized. This is a critical moment that sets the tone for the entire interaction and can greatly influence the outcome. Using real-life scenarios, let’s take a look at some key techniques that make first impressions count.

  • Cultural sensitivity when greeting people
  • The power of body language
  • Build relationships
  • Maintain eye contact
  • Self-relaxation techniques
  • Strategic self-preparation
  • Practice patience and diplomacy
  • Focus on adding value
Cultural sensitivity when greeting people

It is important to take cultural characteristics into account when greeting your interlocutors. For example, in some cultures a handshake may be a common greeting, while in others a bow or namaste may be more appropriate. Imagine a scenario where a candidate, knowing the interviewer’s cultural background, initiates the conversation respectfully and in line with their own habits. This demonstrates cultural awareness and has a positive impact on the interview.

 

The power of body language

A firm yet gentle handshake can convey trust and professionalism. Imagine a candidate walking into the interview room with a warm smile and a handshake that conveys kindness and firmness. This simple gesture can leave a lasting impression on the interviewer and signal that the candidate is confident and capable.

 
Build relationships

Building a relationship with your interview panel can help reduce tension and create a more relaxed atmosphere. For example, chatting before a formal interview begins can help break the ice and foster camaraderie. Imagine a scenario where a candidate starts a conversation with one of the panelists about a common interest, instantly building a rapport and making the interview feel more like a conversation than an interrogation.

 

Maintain eye contact

Consistent eye contact during the interview shows confidence, focus, and sincerity. Imagine a candidate who communicates honesty and transparency by making consistent eye contact with each panel member while speaking. These nonverbal cues can promote trust and credibility in the interviewer.

 

Self-relaxation techniques

It’s natural to feel nervous before an interview, but it’s important to find ways to calm your mind. One trick is to talk to other people in the waiting room to distract yourself from anxious thoughts. Imagine a scenario where a candidate strikes up a conversation with another interviewer, shares anecdotes and laughs, relaxes before the interview, and arrives at the interview in a calm manner.

 

Strategic self-preparation

An interview is essentially a sales conversation where the candidate is the product. Therefore, it is important to present your skills, experience, and achievements persuasively. Imagine a candidate who skillfully crafts their responses to highlight their strengths and accomplishments and effectively “sells” themselves as the ideal candidate for the position.

 

Practice patience and diplomacy

Interviewers may ask odd questions or test the applicant’s patience to gauge temperament and problem-solving skills. In such situations, it is important to remain calm and respond tactfully. Imagine a scenario where an interviewer asks a difficult question and the candidate responds with grace and confidence, turning an obstacle into an opportunity to demonstrate resilience and adaptability.

 

Focus on adding value

Ultimately, interviewers are looking for candidates who can make a positive contribution to the organization. It’s important for candidates to tailor their answers to the company’s needs and demonstrate how they can add value. Imagine a candidate who not only answers questions clearly, but is also willing to actively discuss his or her ideas and make meaningful contributions to the company.

By implementing these principles and strategies, candidates can make a lasting impression on interviewers and increase their chances of landing the opportunity they want. Remember: First impressions set the stage, but it’s the entire interview experience that ultimately determines success.

Mastering Your Preparation for Success

The key to success in your next interview is preparation. It is important to carefully review all aspects of your resume and check the company website in advance. Interviewers typically focus questions on your resume and related topics. Therefore, it is important to thoroughly understand everything on your resume.


Rather than copying other resumes, try to express yourself authentically. Personalize your resume to reflect who you really are and remove unnecessary information. A one-page resume is often preferred for new employees, but a two-page resume may be more appropriate for experienced applicants.


Some may be uniquely qualified, but meeting specific standards is not required. Create your own unique style by incorporating your personality. Avoid duplication in your resume and be clear. Interviewers can recognize repeated information.


Online business research is a valuable activity. Gain a basic understanding of the company, especially its flagship products or key initiatives. Although it is beneficial to have in-depth knowledge, it is not necessary to delve into every aspect of a company’s operations.


When it comes to salary negotiations, it’s important to approach the topic with sensitivity and realism. Look for salaries similar to your position and seek professional advice if necessary. Aim for a reasonable price that meets industry standards and your company’s budget constraints.


Real life example:

As a marketing professional preparing for an interview at a leading technology company, Sarah carefully reviews her own resume and ensures that all of her accomplishments and skills are effectively highlighted. Instead of emulating her generic role models, Sarah infuses her own resume with her own unique experiences and personality, demonstrating her creativity and strategic thinking.


As Sarah researched her company, she learned more about its innovative product line and recent market success. Even though she doesn’t go into technical details, she gains a solid understanding of the company’s brand and values.


During her interview, Sarah is asked what her salary expectations are, and she shows her professionalism by suggesting a figure that fits industry standards and company terms. She was impressed by his thorough preparation and genuine approach, and she ultimately secured his position.

Stand out by expressing your uniqueness and value proposition

In today’s competitive job market, landing your dream position often means competing against a variety of equally qualified candidates. Imagine a scenario where hundreds of resumes flood a hiring manager’s desk, all competing for the same coveted position. While many applicants have similar qualifications on paper, it is the intangible qualities that set you apart that define your character, work ethic, and potential contribution to the company.

Consider the following: You are applying for a marketing manager position at a leading technology company. There are many other candidates with similar degrees, certifications, and industry experience as you. But what truly sets you apart is your natural creativity, strategic thinking, and passion for leveraging digital platforms to drive brand engagement.

During the interview, it is important to explain why the company should choose you over others. It’s not just about recreating your resume. This is a clear articulation of your unique value proposition. Your knowledge, attitude, commitment to the job and communication skills play an important role in demonstrating why you are the right person for the job.

Let’s look at these aspects in more detail.

  • Awareness of Current Affairs
  • Knowledge
  • Attitude
  • Commitment
  • Communication Skills
  • Technical skills

 

Awareness of Current Affairs:

Demonstrating an understanding of current events and industry developments demonstrates your commitment and relevance. Show your commitment to staying ahead of the curve by staying up to date with relevant news, market trends and developments in your field.

 

Knowledge:

Demonstrate expertise in your industry, including technical expertise, industry trends, and expert knowledge. For example, if you’re applying for a software development job, talk about your knowledge of programming languages and your familiarity with cutting-edge technologies.

 

Attitude:

Your attitude can change the game. Employers value applicants who demonstrate enthusiasm, adaptability, and a willingness to learn. Share anecdotes that highlight your proactive approach, problem-solving skills, and resilience in difficult situations.

 

Commitment:

Employers value applicants who are committed to excellence. B. Provide examples of situations where you have demonstrated commitment, such as taking on additional responsibilities, completing a project early, or investing in ongoing training and professional development.

 

Communication Skills:

Effective communication is essential in every role. Emphasize your persuasive communication skills and ability to build relationships with stakeholders, such as communicating ideas clearly, actively listening to others, or working effectively as a team.

 

Technical skills:

In today’s digital age, many roles require knowledge of basic Internet usage, office applications, and computer skills. Emphasize your familiarity with relevant software tools and your ability to adapt smoothly to new technologies.

Remember, the goal is not only to meet the hiring manager’s expectations, but to exceed them. Treat every interview as an opportunity to showcase your strengths, personality, and potential contributions to the company. By presenting yourself as authentic and trustworthy, you will stand out from the crowd as your favorite candidate.

 

Have a positive attitude to make a good impression on the interviewer

In a competitive interview environment, a positive attitude can greatly increase your chances of success. Just as people are naturally attracted to people who exude optimism and enthusiasm in their daily interactions, interviewers are also attracted to candidates who exude a positive attitude. This quality not only reflects your personal appearance, but also says a lot about your potential fit with the company culture and team dynamics.


Imagine the following scene: As you enter the interview room, you are greeted by a group of solemn-looking experts. Even if you’re nervous, consciously maintain a positive attitude, a warm smile, and a charming demeanor. During the interview, use every opportunity to express your genuine interest in the position and enthusiasm for the challenges it presents. Your optimistic attitude shines through when discussing possible night shifts, overtime, or other difficult aspects of the job, demonstrating your willingness to face challenges and contribute fully to the organization.


In contrast, imagine a candidate who doesn’t like unconventional work hours or extra responsibilities and approaches the interview with a negative attitude. Their lack of enthusiasm and pessimistic attitude may cause the interviewer to question their suitability for the position. In these cases, despite the necessary qualifications, a candidate’s negative attitude can ultimately overshadow their potential and influence jurors to favor the more optimistic candidate.


It’s important to recognize that in today’s dynamic job market, employers are looking for people who not only have the necessary skills and qualifications, but also demonstrate the right attitude and mindset. By displaying a positive attitude during the interview, you not only demonstrate your willingness to accept challenges, but also your willingness to make a positive contribution to the organization’s goals.


Moreover, a positive attitude doesn’t mean you completely ignore your own personal preferences or happiness. Rather, it is important to take a flexible and adaptable approach and be willing to make the compromises necessary to grow and develop professionally. This may mean agreeing to work nights, working overtime when necessary, or taking on additional responsibilities to achieve your career goals.


Basically, maintaining a positive attitude during an interview will not only increase your likeability, but it will also help emphasize your suitability for the job. Exuding optimism, enthusiasm and a willingness to take on challenges, you will establish yourself as a valuable asset to any organization, able to thrive in a diverse work environment and contribute significantly to its success. So, don’t forget to harness the power of positivity in your next interview. This could be the key to opening up exciting opportunities and advancing your career.

 

Master Body Language for Success

As the saying goes, “Man is a creature of habit.” In fact, each of us has personal habits, some of which may inadvertently project negative attitudes onto others. Imagine this scenario. You’re sitting at a job interview, lost in thought, and start unconsciously tapping your foot. Even though this behavior may seem harmless to you, it can leave a lasting negative impression on the interviewee.

 

Body language often says more than words. Simple gestures such as crossing your arms, frequently touching your face or hair, or picking your beard or nose can convey nervousness, insecurity, and even dishonesty. Even if these practices are unintentional, they can undermine your credibility and suitability for the job.

Interviews present unique challenges that go beyond simply discussing qualifications or experience. Some interview panels explore the world of personal reflection through questions designed to assess internal perspectives. These surveys often aim to move away from the technical aspects of the job and assess an individual’s personality and behavior under pressure.

Imagine a scenario where a job seeker is faced with the question, “What is your greatest weakness?” or “What would your last boss say about you?” These questions are not routinely asked of all candidates. Rather, it is used strategically by interview teams to make decisions about potential employees.

This approach is disarming, but it is an important time for the candidate to demonstrate their ability to remain calm and professional regardless of the situation. It is a test not only of technical skills, but also of emotional intelligence and self-awareness.

For example, imagine a candidate who, when asked what his weaknesses are, answers honestly and humbly, recognizes opportunities for improvement, and emphasizes personal development strategies. This response shows not only confidence but also a willingness to take on the challenge.

Moreover, remaining calm and collected in such situations speaks volumes about a person’s ability to cope with workload and adversity. Demonstrate flexibility and adaptability, traits that employers value in today’s fast-paced, dynamic workplace.

Basically, the ability to control yourself in difficult situations is a valuable skill that will take you beyond the limits of an interview. It’s a testament to a person’s character and ability to grow, and sends a signal to potential employers that the candidate can be trusted to handle uncertain situations with grace and professionalism. So while these unexpected questions may surprise applicants, they’re also a great opportunity to demonstrate your desire to excel in all situations.

 

Prepare for your interview with common questions:

Prepare for your interview by thoroughly practicing your answers to the most common interview questions. Participate in an intensive practice session to anticipate and develop answers to common interview questions. The following questions serve as a starting point, but your preparation should include as many different questions as possible.

Practicing answering these questions will refine your pronunciation, increase your confidence, and improve your interview performance. Consider the following real example:

  • Tell me about yourself?
  • Express yourself?
  • Give a short description about you?
  • How would you describe yourself?
  • What makes you unique?
  • How do we know that you are unique?
  • Why do you want to work here?
  • Why do you choose us?
  • What are you passionate about?
  • What criteria bring you here?
  • What interests you about this role?
  • Which interesting part of the job attract you most?
  • What motivates you?
  • What are your greatest strengths?
  • Show me your strength?
  • Why are you leaving your current job?
  • Which specific cause lead you here?
  • Tell us about your shortcoming and how can you overcome it?
  • What are your extreme weaknesses?
  • What are your goals for the future?
  • What is your future plan?
  • Where do you see yourself in five years?
  • Do you like to stay in same position after ten years?
  • Which type of work you don’t like to perform?
  • Can you tell me about a difficult work situation and how you overcame it?
  • Are face any type of unwanted situation?
  • What is your salary range expectation?
  • Are you interested to join with us below your current salary?
  • Why should we hire you?
  • Tell me the reason why I should hire you?
  • Do you have any questions?
  • What did you like most about your last position?
  • What did you like least about your last position?
  • How do you handle stress?
  • How do you handle conflict at work?
  • Why are you interested in this position?
  • What is your greatest accomplishment?
  • How do you define success?
  • How do you work under pressure?
  • What is your dream job?
  • What can you bring to the company?
  • What skills would you bring to the job?
  • What does customer service mean to you?
  • Tell me about your work experience?
  • Tell me about your extracurricular activities
  • What is your favorite game?
  • How do you spend your leisure time?
  • Are you involve in political activities?
  • Who is your favorite Leader?

Imagine you are preparing for an interview at a well-known technology company. Anticipate questions, reflect on your experiences, and formulate your answers. For example, if you are asked what your strengths and weaknesses are, list your strengths, such as your ability to solve problems and your proactive approach to learning new technologies. Instead, you recognize a tendency to be overly detailed as a weakness, but emphasize an ongoing effort to delegate tasks effectively. Through repeated practice, you will not only develop sophisticated answers, but you will also gain deeper insight into your skills and be able to express yourself authentically in interviews.

Interview Tips in Pharmaceuticals and other Renowned Company Read More »

Form 483,difference between FDA Form 483 & Warning Letter?

Form 483, after the application to FDA, the FDA send Inspector to the pharmaceutical pharm to inspect the applicant pharm. After complete the inspection, the inspection team note down their observations and communicate to the pharm for audit response in a specific form. The form used by the FDA inspection team to note down their observations, this official form is known as FDA Form 483[or simply 483].

Concisely, this is actually an official form issued by the FDA [Food and Drug Administration] Inspector not FDA office. The inspection team just issue this form to the firm for audit response just after completion of the auditing process at the site of the firm. This observation is not readily published the FDA website due to this is the preliminary assessment for the respective firm and the inspection team just want the explanation to the firm for their daily activities regarding cGMP compliance.

Sometimes local or international newspaper release the news that a respective company received 483. Almost everybody considered it as bad news for the company. Yes, this is really a bad news for the company when company failed to response positively against 483 then it leads to withhold the production of the site even license cancelled and shutdown of the activities of the firm.

At the time of the inspection of the firm, the FDA Inspector generally seek for cGMP compliance to the firm. All of the significant observations are recorded on the FDA form 483 and measures must take based on this observation. 15 working days are the timeframe to response this observations.

An EIR [Establishment Inspection Report] is always issued just after site audit along with or without FDA Form 483. 483 may be issue or not depend on the culture of cGMP compliance of the firm but FDA inspector must issue an EIR. The EIR must be response within 30 working days.

form 483

An EIR consist of the following things:

No Action Indicated (NAI) means that no relevant conditions were found during the site investigation. In practice, this means that the regulator has carefully examined the site and determined that it complies with relevant standards and regulations. For example, if routine inspections of a drug manufacturing facility do not uncover problems that affect product quality or safety, the FDA may issue an NAI rating indicating that no further action is needed.

On the other hand, VAI (Voluntary Action Indicated) means that a situation of minor offense has been discovered that must be resolved voluntarily by the company involved, even if immediate regulatory intervention is not required. For example, if an inspection of a food processing plant reveals minor differences in hygiene standards, regulators may issue a VAI rating and require the company to voluntarily correct the problems.

OAI (Official Action Indicated) is a classification given when an examination reveals a serious and undesirable condition requiring immediate regulatory action. In real-world situations, if a medical device manufacturing facility is found to have significantly deviated from quality standards, regulators may issue an OAI classification and require rapid corrective action to ensure public safety.

After FDA Form 483 is issued, the company’s senior management has 15 business days to respond and provide comments and an action plan. The FDA will then evaluate the proposed plan to determine its acceptability. If the FDA finds serious non-compliance, it can re-inspect the company to ensure that corrective actions were actually implemented. This iterative process ensures compliance with regulatory standards and protects public health.

Effect of FDA Form 483 on NDA or ANDA

During NDA or ANDA CMC reviews, the reviewer requests FDA Field Operations for information on the applicant firm’s compliance status. If a positive response is received, the CMC reviewer proceeds with further actions, expediting the application and leading to a positive approval decision. This process is referred to as PAI (Pre-Approval Inspection).

When evaluating a New Drug Application (NDA) or Abbreviated New Drug Application (ANDA), Chemistry, Manufacturing, and Controls (CMC) investigators work with FDA field operations teams to identify nonconforming or unsatisfactory test results. Agency. In fact, this important step includes a comprehensive evaluation of the manufacturing processes, quality control, and overall regulatory compliance of the pharmaceutical company applying for approval of a new drug.

For example, let’s say XYZ Pharmaceuticals, a pharmaceutical company, submits an ANDA for a generic version of an existing drug. CMC investigators responsible for evaluating the technical and manufacturing aspects of the request will work with FDA field operations to determine whether the XYZ Pharmaceuticals facility has already been inspected. This includes ensuring compliance with Good Manufacturing Practices (GMP) and other regulatory standards.

If the FDA field operations team provides a positive response indicating satisfactory results or compliance from a previous inspection, this clears the way for CMC examiners to proceed with the Pre-Approval inspection (PAI) process. PAI is an important step in which the FDA conducts an on-site inspection of the requesting company’s facility to ensure that its manufacturing processes meet regulatory requirements.

A positive response from the FDA field operations team will expedite the entire NDA or ANDA application process. This acceleration is due to the trust gained from previous positive visits, which in turn contributes to faster decision making. Finally, positive preapproval findings increase the likelihood of a positive approval decision for a drug application and highlight the important role compliance and preapproval records play in the drug regulatory approval process.

 

How to handling the FDA Form 483?

After completion of the inspection, discus the observation with the FDA Inspectior. If possible resolve the negative issue before leaving the FDA inspector.

  • Convince the Inspector about any other minor issue to resolve.
  • Try to understand the attitude of Inspector and know how about your firm.
  • Repeat the question politely if you are trouble to realize the issue
  • Try to avoid any confusion regarding audit observations
  • Try to avoid similar type of observations by consulting with the inspector
  • Try to response FDA Form 483 within 15 working days
  • Always be polite with the Inspector and never try to impose any issue.
  • Avoid any type of conflict with the inspector
  • All issues must be clarify from the Inspector.
  • Try to understand their demand regarding the current observations.
  • Never exhibit over smartness to the Inspector due they are smart enough to handle any situations.

What is Warning Letter?

FDA Form 483 may follow a warning letter for cGMP issues related to product quality and safety. FDA requires prompt response and justification. Failure to do so may result in a ban. Warning letters typically result from serious cGMP violations. More information is posted on the FDA website.

After issuing FDA Form 483, regulators may escalate their response by issuing a warning letter. This is especially true if observations reveal significant Good Manufacturing Practices (cGMP) issues that impact product quality and safety. It is important to note that the FDA has ongoing efforts to maintain product quality standards and prioritize consumer safety. If significant issues are identified, the FDA may issue a warning letter with detailed comments.

When is an FDA Form 483 issued?

FDA Form 483 issued after the completion of the inspection to the specific firm to notify the violation of FD&C[Food Drug and Cosmetic] Act & its related acts. Generally, the trained FDA inspectors observed that the Food, Drugs, Device or Cosmetic has been prepared its standard practice, any type of cGMP violations goes to issuance of 483.

FDA Form 483 is issued following completion of an inspection and serves to formally notify a company of violations of the Food, Drug, and Cosmetic (FD&C) Act and related regulations. This important document is typically prepared by trained FDA investigators who carefully examine a company’s manufacturing processes involved in producing food, drugs, devices, or cosmetics.

FDA Form 483 is an important regulatory tool used to address deviations from established standards and practices. These deviations are often related to compliance with current good manufacturing practices (cGMP), which serve as a set of guidelines to ensure the quality, safety and effectiveness of products in industries under FDA jurisdiction.

To illustrate, consider a hypothetical pharmaceutical company that is under FDA investigation. Knowledgeable and professional inspectors inspect various aspects of business operations, from handling raw materials to packaging the final product. If the inspection reveals deviations from cGMP, such as deficiencies in controls, inadequate documentation, or noncompliance with established procedures, FDA inspectors will record these findings on FDA Form 483.

For example, if an inspector finds that a drug manufacturing facility does not maintain a sterile environment when manufacturing injectable drugs, this will be recorded on FDA Form 483. The company is then notified of the violation by issuing the appropriate form. It outlines specific areas of non-compliance and requires the company to immediately correct identified issues.

Although FDA Form 483 is not a formal enforcement action, it is an important tool for reporting deficiencies and encouraging corrective action. We urge companies to voluntarily take corrective action to address identified violations, prevent potential public health risks, and ensure continued compliance with regulatory standards. Typically, companies must respond to the FDA detailing the corrective action they intend to take. The agency may conduct a follow-up investigation to determine the effectiveness of such corrective action.

 What is the purpose of an FDA Form 483?

The only purpose of the FDA Form 483 is to notify the firm management about the objectionable conditions and discuss with the objectionable conditions with the senior site management team. FDA always encourage the management to response the form 483 in writing with appropriate action plan and implement the same within due time frame.

The primary purpose of FDA Form 483 is to inform a company’s management of conditions deemed inadequate during an investigation. This form serves as an important communication tool between FDA and field senior management teams and facilitates comprehensive discussion of identified issues. A key aspect of this process is that the FDA requires management to provide a written response to Form 483 with a thoughtful plan of action.

Imagine a pharmaceutical manufacturing facility that is actually inspected by the FDA. If the inspector finds a deviation from regulatory standards, that deviation is documented on Form 483. For example, if there is a defect in the manufacturing process that could affect the quality and safety of the drug, the FDA uses the form to communicate those concerns to management. .

Upon receipt of Form 483, pharmaceutical company executives will meet to discuss any suspicious conditions identified. In response to the form, FDA actively encourages written feedback from management outlining a detailed action plan to address issues raised in the inspection. This written response represents an important step and demonstrates the company’s commitment to address and resolve the concerns raised by the FDA.

For example, management may commit to implement an improved quality management system, review standard operating procedures, or invest in improved equipment to ensure compliance with regulatory standards. Written feedback is not only a means of communication, but also strong evidence of a company’s commitment to quality and compliance.

FDA also emphasizes the importance of timely implementation of the proposed action plan. This highlights the urgent need to immediately address unlawful situations, mitigate potential public health risks and ensure companies meet regulatory expectations. The entire process involves collaboration between the FDA and regulated companies and promotes continuous improvement of manufacturing practices and compliance with regulatory guidelines.

Difference between FDA Form 483 and Warning Letter
FDA Form 483Warning Letter
A FDA Form 483 is issued just after completion of the applicant site auditing process by FDA Inspector(s)Warning letter issues after finding of serious cGMP non-compliance
It consists of List of observations found during auditing process.It consists of List of regulatory significance observations found during auditing process.
It issues by the FDA inspector after completion of the site audit. It issues from the FDA office based on serious Regulatory non-compliance
A firm may face to FDA Form 483 due to his bad cGMP practiceWarning Letter(s) issues where serious non-cGMP practice done especially regarding product quality
FDA Form 483 response must be complete within 15 working daysWarning Letter response must be complete within 30 working days
FDA Form 483 observations may be deleted at the site upon discuss with FDA Inspector if satisfactory answer may be deliveredA warning letter can’t be refuse/reject/resolve without proper justification

 

Is the FDA Form 483 list of every possible deviation from law and regulation?

When it comes to FDA inspections, it is important to note that any unknown or questionable observations are carefully documented on FDA Form 483. This form is an important tool during the inspection and contains a complete record of observed conditions that cause concern or require explanation. Importantly, the scope of FDA Form 483 goes beyond listing observations during the inspection.

Specifically, FDA Form 483 captures real-time inspection results as well as suspicious conditions that may be present in the facility but not necessarily observed during the inspection. This comprehensive approach increases transparency and accountability in the inspection process by thoroughly documenting any potential risks or deviations from regulatory standards.

For example, imagine a pharmaceutical manufacturing facility undergoing FDA inspection. Although the inspector may note some deviations from good manufacturing practices during the actual inspection, FDA Form 483 goes beyond these immediate observations. This provides a platform to address and document any concerns or existing conditions that may impact product quality or compliance but were not clearly identified during inspection.

By including a wide range of illegal conditions on FDA Form 483, regulators can work with inspection companies to effectively implement corrective and preventive actions. This approach not only provides a more holistic understanding of the compliance environment, but also drives continuous improvement within regulated sectors.

Simply put, FDA Form 483 is a dynamic and comprehensive document that goes beyond simple real-time observations during an inspection. It serves as a repository for all known and potential criminal situations and provides a thorough and transparent assessment of a facility’s compliance with regulatory standards. This proactive approach ultimately helps improve overall product quality, patient safety, and compliance in the industries being audited.

How is the FDA Form 483 communicate with the company?

After completion of the inspection, the FDA Inspector(s) discussed the factory management in read and discuss until fully understood by the senior management to clarify the objectionable matters.

Form 483,difference between FDA Form 483 & Warning Letter? Read More »

Definition of GMP according to different Pharmaceutical guideline

Definition of GMP according to WHO guideline

Definition of GMP: “Good manufacturing practice (GMP) is that part of quality assurance which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the marketing authorization.”

definition of GMP

 

Definition of GMP according to US FDA Guideline

CGMPs provide for systems that assure proper design, monitoring, and control of manufacturing processes and facilities. Adherence to the CGMP regulations assures the identity, strength, quality, and purity of drug products by requiring that manufacturers of medications adequately control manufacturing operations. This includes establishing strong quality management systems, obtaining appropriate quality raw materials, establishing robust operating procedures, detecting and investigating product quality deviations, and maintaining reliable testing laboratories. This formal system of controls at a pharmaceutical company, if adequately put into practice, helps to prevent instances of contamination, mix-ups, deviations, failures, and errors. This assures that drug products meet their quality standards.

definition of GMP
 
Definition of GMP according to TGA Guideline

“Good Manufacturing Practice (GMP) describes a set of principles and procedures that when followed helps ensure that therapeutic goods are of high quality. A basic tenet of GMP is that quality cannot be tested into a batch of product. Quality must be built into each batch of product during all stages of the manufacturing process”

definition of GMP
 
Definition of GMP according to UK MHRA guideline

Good manufacturing practice (GMP) is the minimum standard that a medicines manufacturer must meet in their production processes. Products must:

  • be of consistent high quality
  • be appropriate to their intended use
  • meet the requirements of the marketing authorisation (MA) or product specification
definition of GMP
According to WHO

“GMP covers all aspects of the manufacturing process: defined manufacturing process; validated critical manufacturing steps; suitable premises, storage, transport; qualified and trained production and quality control personnel; adequate laboratory facilities; approved written procedures and instructions; records to show all steps of defined procedures taken; full traceability of a product through batch processing records and distribution records; and systems for recall and investigation of complaints”.

 

What is GMP?

Good Manufacturing Practices (GMP) are a set of strict guidelines and principles used by pharmaceutical companies to ensure consistent production of safe, high-quality pharmaceutical products. These guidelines are important to maintain the integrity of manufacturing processes, maintain public health standards, and comply with regulatory requirements from global health authorities such as the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA). ) Europe. Below is a closer look at the key aspects of GMP in the pharmaceutical industry.

 

  • Documents and Records
  • Quality management system
  • Staff training
  • System and device maintenance
  • Validity and Acceptability
  • Raw material inspection
  • Process control
  • Quality control and testing
  • Traceability and withdrawal procedures
 
Documents and Records:

Complete and accurate documentation is critical to GMP. It includes detailed records of manufacturing processes, procedures and results. For example, pharmaceutical companies carefully record every step of the production of a particular drug, from raw material supply to final packaging.

Thorough and accurate documentation of good manufacturing practices (GMP) plays an important role. This involves carefully recording various aspects of production, including processes, procedures, and results. Take the pharmaceutical industry, for example, where pharmaceutical companies take great care to document every critical step in the production of a particular drug.

In compliance with GMP standards, the documentation process begins with detailed records of raw material procurement. Pharmaceutical companies carefully record information about the origin, quality, and quantity of each raw material used in the pharmaceutical manufacturing process. This documentation is not only essential for quality control, but also serves as the basis for traceability and allows the company to identify and correct any problems that arise during the production cycle.

Each step in pharmaceutical manufacturing is accurately documented as the manufacturing process progresses. This includes information about the equipment used, environmental conditions, and deviations from standard procedures. For example, if specific temperatures or pressures are important for a particular production step, these parameters are recorded to ensure consistency and reproducibility.

In addition to manufacturing processes, GMP documents also contain procedures that control various aspects of manufacturing. This includes standard operating procedures (SOPs) for equipment calibration, cleaning protocols, and employee training. Pharmaceutical companies ensure that these procedures are not only fully documented but also regularly updated to reflect improvements or changes in industry regulations.

Outcomes such as product quality and test results are also carefully documented within the GMP framework. Pharmaceutical companies keep detailed records of the quality control tests performed at various stages of manufacturing. This document is an important tool during regulatory investigations and demonstrates the company’s commitment to producing safe and effective medicines.


GMP documentation also extends to final packaging. From the materials used in packaging to the labeling process, every detail is recorded to ensure compliance with regulatory requirements and ensure the safety of end users. This comprehensive document will help you not only comply with regulatory standards, but also improve overall product quality and compliance.

In summary, the importance of complete and accurate documentation in the GMP area cannot be overemphasized. The pharmaceutical industry’s commitment to documenting all aspects of the manufacturing process, from raw material procurement to final packaging, not only ensures regulatory compliance, but also promotes a culture of continuous improvement, quality assurance, and accountability within the industry.

 
Quality management system

A robust quality control system is implemented to monitor all aspects of manufacturing, testing and quality control. This involves creating and maintaining processes to consistently produce pharmaceutical products that meet predetermined quality standards.


Establishing and maintaining a strong quality management system plays a critical role in ensuring complete oversight of all aspects of the manufacturing, analytical and quality control processes in the pharmaceutical industry. This system has been carefully designed to create a facility that consistently produces pharmaceutical products that meet stringent predetermined quality standards.

To better understand the importance of these systems, let us consider a real-world example from a pharmaceutical manufacturing plant. The introduction of a quality management system involves careful documentation and standardization of production processes. This includes everything from raw material collection and storage to the actual manufacturing process.

For example, if you produce life-saving pharmaceuticals, your quality management system establishes clear protocols for sourcing and verifying raw materials. This may include rigorous testing and certification processes to ensure the purity and integrity of ingredients used in pharmaceutical formulations.

Once the manufacturing process begins, quality control systems monitor each step to ensure compliance with predetermined standards. This may include real-time data monitoring, automated quality checks, and routine inspections to identify and address deviations from established protocols.

Testing is another important step and a quality management system ensures that rigorous testing procedures are implemented. This may include a variety of analytical techniques, such as chromatography or mass spectrometry, to test the structure and efficacy of the drug. The system also monitors environmental conditions such as temperature and humidity to ensure the stability and functionality of the final product.

Quality control measures within the system go beyond manufacturing and include aspects such as packaging and labeling. For example, in the pharmaceutical manufacturing case, quality control systems enforce standards for proper labeling, tamper-evident packaging, and verification of expiration dates to protect end users.

Regular audits and reviews are an essential part of this system. This allows you to continuously evaluate performance and identify areas for continuous improvement. By implementing a strong quality management system, pharmaceutical companies not only comply with regulatory requirements, but also build trust among consumers, healthcare professionals, and regulators regarding the safety and effectiveness of their products.

 
Staff training

GMP requires that all employees involved in the manufacturing process receive extensive training. This ensures that employees are fully familiar with the processes and requirements associated with their role. For example, people working in quality control must be trained to perform accurate and reliable testing on pharmaceutical products.

Compliance with Good Manufacturing Practices (GMP) requires in-depth training for all employees involved in the production process and emphasizes the importance of ensuring high levels of employee efficiency and performance. This rigorous training program aims to provide employees with a deep understanding of the specific procedures and requirements associated with their respective roles within a manufacturing facility.

For example, quality control personnel play a key role in ensuring compliance with GMP standards. Our extensive training program provides these individuals with the skills and knowledge necessary to perform accurate and reliable pharmaceutical testing. This includes training in the use of state-of-the-art testing equipment, adherence to established testing protocols, and the ability to accurately interpret and analyze test results.

The training not only covers technical aspects, but also emphasizes the importance of a strong awareness of quality standards and compliance. This comprehensive approach ensures that quality control personnel not only perform their duties properly, but also understand the broader context of GMP regulations and their role in ensuring the overall quality and safety of pharmaceutical products.

Additionally, GMP training goes beyond specific job functions to include broader concepts such as sanitation, documentation practices, and safety protocols. For example, production workers are trained in proper dressing procedures and hygiene practices to prevent contamination during manufacturing. Training programs may also include modules on documentation standards to ensure accurate records of all manufacturing activities, which are important for traceability and compliance.

By investing in extensive training, companies not only meet legal requirements, but also instill a culture of excellence and responsibility in their employees. In turn, this contributes to the overall reliability and integrity of the manufacturing process and ultimately promotes the quality and safety of the medicines delivered to consumers.

 

System and device maintenance

Regular maintenance of plant and equipment is essential to prevent contamination and maintain the accuracy of manufacturing processes. A practical example is planning regular inspection and maintenance of pharmaceutical manufacturing equipment to prevent defects that could affect product quality.

Regular maintenance of plant and equipment is essential to prevent contamination and maintain the accuracy of production processes. A prime example of this need is strategic planning for regular inspection and maintenance of machinery used in pharmaceutical manufacturing. Implementing a proactive maintenance approach allows you to quickly identify and resolve potential defects that could compromise the quality of the final product.

In the pharmaceutical industry, where precision and purity are top priorities, continuous operation of special equipment is very important. A regular maintenance routine, including thorough inspection and maintenance, becomes an essential part of a strong quality assurance system. For example, in pharmaceutical manufacturing plants, complex machinery such as tablet presses, mixers, and encapsulation machines must be inspected regularly to ensure they are operating within set parameters.

A practical example of the importance of regular maintenance can be seen through the example of a tablet press used to produce pharmaceutical tablets. Regular inspections include a complete inspection of machine components such as: B. Tools, pressure rollers and feeding systems. Maintenance activities include lubrication, calibration, and replacement of worn parts.

Following a proactive maintenance plan can help you identify potential problems early, such as wear, deformation or risk of contamination. Resolving these issues in a timely manner helps prevent unexpected errors and reduce downtime in the manufacturing process. This not only ensures consistent quality of medicines, but also contributes to operational efficiency and cost-effectiveness.

 

In essence, proactive maintenance of plant and equipment, including through regular inspections and maintenance, plays a key role in the pharmaceutical manufacturing process. This approach not only protects against contamination, but also ensures the precision needed to maintain the highest product quality in industries where reliability and compliance are paramount.

 
Validity and Acceptability

GMP requires verification and qualification of equipment, processes and systems to ensure efficiency and consistency. For example, pharmaceutical companies can ensure that a particular manufacturing process consistently produces drugs that meet required specifications.

Good Manufacturing Practices (GMP) require a thorough verification and qualification process of equipment, processes and systems to ensure efficiency and consistency. These rigorous verifications ensure that our manufacturing operations meet established standards and consistently deliver high-quality products.

For example, consider a pharmaceutical company that produces drugs. By adhering to GMP principles, the company will control preventive measures in certain manufacturing processes. This validation process includes extensive testing and analysis to ensure that the manufacturing process consistently produces medicines that meet regulatory authorities’ rigorous specifications and quality standards.

During this validation process, pharmaceutical companies carefully evaluate various parameters such as raw material specifications, device performance, environmental conditions, and process controls. The goal is to provide evidence and documentation that the manufacturing process consistently produces a drug with the desired properties, ensuring safety, efficacy, and quality of the final product.

Moreover, this verification process is more than an isolated event. It is a constant effort to continuously improve. Regular assessments, redesigns and updates ensure good processes remain effective and aligned with evolving industry standards. This proactive approach not only ensures GMP compliance, but also increases the overall efficiency and reliability of pharmaceutical manufacturing, helping to deliver safe and effective medicines to consumers.

 
Raw material inspection

We apply rigorous procedures to check and test our raw materials to ensure they meet our quality specifications. In fact, pharmaceutical manufacturers can test the purity, potency, and other relevant characteristics of incoming raw materials before incorporating them into the manufacturing process.
Strict protocols are in place to control and test raw materials to ensure stringent quality specifications are met. A great example of this delicate process can be seen in the pharmaceutical industry, where manufacturers carefully test incoming raw materials for a variety of important characteristics such as purity and potency. These raw materials undergo extensive testing to ensure they meet the highest standards before being incorporated into the manufacturing process.

Implementing robust testing procedures in pharmaceutical manufacturing requires evaluating raw materials against predetermined criteria to ensure quality and suitability for use. For example, pharmaceutical companies may use advanced analytical techniques such as chromatography or spectroscopy to analyze the purity of compounds in their raw materials. This ensures that the ingredients meet the required specifications and do not contain impurities that could compromise the safety and functionality of the final product.

 

Moreover, efficacy testing is an important aspect of the evaluation process, especially for drugs where precise dosing is important for therapeutic efficacy. Manufacturers can accurately measure the active ingredients in their raw materials using sophisticated methods such as high-performance liquid chromatography (HPLC) or mass spectrometry.

In addition to assessing purity and potency, other relevant characteristics such as particle size, moisture content, and microbial contamination can also be examined in depth. This multi-layered approach ensures a complete evaluation of raw materials and does not allow for any compromise in the quality of the final drug product.

By implementing these rigorous testing procedures, pharmaceutical manufacturers not only comply with legal requirements, but also emphasize the production of safe, high-quality drugs. Effective control and analysis systems are essential to ensure that raw materials used in the pharmaceutical industry meet the high standards required to develop reliable and effective medical solutions.

 
Process control

GMP emphasizes implementing controls at various stages of the manufacturing process to ensure consistency and quality. This may involve monitoring critical process parameters in real time to immediately detect and correct deviations.
Good manufacturing practices (GMP) place great importance on the careful application of stringent controls throughout the manufacturing process to ensure consistency and high quality of the final product. This comprehensive approach includes continuous real-time monitoring of critical process parameters, allowing deviations from set values to be immediately detected and corrected.

For example, in the pharmaceutical industry, GMP compliance is essential to ensure safe and effective drug production. Various critical parameters such as drug preparation time, temperature, pressure, and chemical concentration are monitored in real time. If any of these parameters fall outside the specified range, the automated system will raise an alert so operators can take immediate action to correct the problem. This proactive monitoring and timely corrective action not only ensures product quality, but also contributes to the overall safety and efficacy of medicines that reach consumers.

In the context of food manufacturing, GMP practices include monitoring issues such as hygiene, temperature, and ingredient ratios. For example, in packaged food production, strict control measures are implemented to maintain hygiene standards at all stages of the production process. Automatic sensors continuously monitor cleaning and, if there are any deviations, initiate an automatic cleaning process to ensure that the end product meets the highest quality and safety standards.

The application of GMP principles extends beyond the pharmaceutical and food industries to a variety of industries, including electronics, cosmetics, and automobile manufacturing. In any case, real-time monitoring of critical parameters and prompt corrective action demonstrates commitment to GMP and ensures consistent production of high-quality products across a variety of industries.

 
Quality control and testing

Intermediate and final products undergo rigorous quality control and testing to ensure they meet specified specifications. This includes extensive testing for aspects such as purity, stability and dissolution rate.

Extensive testing and quality control procedures are systematically implemented throughout the manufacturing process, covering both intermediate and final products. The main purpose is to ensure that these products meet strict quality standards by ensuring that they meet specific specifications. Our testing program is comprehensive and focuses on critical factors such as purity, stability, and dissolution rate that are critical to the overall quality and effectiveness of the end result.

For example, in pharmaceutical manufacturing, intermediate products undergo rigorous testing to assess their chemical purity and ensure that they meet the required pharmacological standards. Stability testing determines a product’s resistance to various environmental conditions, ensuring its effectiveness throughout its shelf life. Additionally, dissolution rate testing is very important, especially for oral drugs. This is because it directly influences treatment results by assessing the amount and speed at which active ingredients are released into the body.

In the electronics industry, strict quality control is applied to final products such as smartphones. Purity testing of electronic components ensures that they meet specified standards, preventing defects or performance issues. Reliability testing is essential to ensure that devices can withstand a variety of environmental conditions without performance degradation. Additionally, testing battery discharge rates ensures consistent and stable power delivery over time, improving the overall reliability of the product.

These examples demonstrate how rigorous quality control and testing processes are essential in a variety of industries to ensure that intermediate and final products always meet specified specifications and ultimately increase customer satisfaction and product reliability.

 
Traceability and withdrawal procedures

GMP requires the establishment of a traceability system to track and recall products in case of quality issues or regulatory violations. Real-world examples include implementing a barcode system to easily identify and recall products in the event of a recall.

Compliance with GMP in the pharmaceutical industry is not only a regulatory requirement, but also a critical factor in protecting public health and maintaining the reputation of pharmaceutical companies. Practical implementation of GMP principles allows careful control of all stages of pharmaceutical production to produce safe and consistently high-quality products.

Good Manufacturing Practices (GMP) mandate the creation of a robust traceability system to monitor and recover products if quality issues occur or deviations from compliance standards occur. A specific example of this need is the integration of advanced barcoding systems into pharmaceutical production processes. This implementation allows for seamless product identification and recovery in recall situations and increases the efficiency and accuracy of the overall process.

Imagine a pharmaceutical company that diligently applies GMP principles to its operations. The company uses cutting-edge barcode technology as part of its tracking system. Each product is assigned a unique barcode, linked to extensive data about production details, ingredients and quality control systems. If there is a quality or non-compliance issue, these barcodes are essential to quickly identify and isolate affected batches.

What is cGMP

To delve deeper into the practical significance, imagine a situation where a particular batch of medicine is suspected to be out of quality standards. GMP-compliant tracking systems allow companies to quickly identify affected products by scanning barcodes, allowing batches to be quickly removed from distribution channels, preventing potential loss to customers. Detailed data associated with the barcode can help you find the root cause of the problem and implement corrective actions to prevent the problem from recurring.

In essence, GMP compliance in the pharmaceutical industry goes beyond regulatory obligations. This is proving to be an important factor in maintaining public health and strengthening the reputation of pharmaceutical companies. Practical implementation of GMP principles, such as the use of advanced tracking systems such as barcodes, implies a commitment to strict control at all stages of the production process. These efforts result in the production of safe, consistent, high-quality medicines that not only ensure regulatory compliance but, more importantly, increase consumer trust and maintain the integrity of the industry.

Definition of GMP according to different Pharmaceutical guideline Read More »

Buffer area and its importance in sterile manufacturing facility

Buffer area is the special zone pharmaceutical company. We can define it the sterile area in pharmaceutical products manufacturing zone where different types of sterile products are manufactured. In a nutshell a buffer area is the area where pharmaceutical products are manufactured. This area is categorized as class 10,000(ISO Class 7) or higher area.

Airborne Particulate classification in Clean Area

EEC GMP
(European Commission)
United States
(209E)
United States
(Customary)
ISO/TC
(209)
WHO
(GMP)
Grade AM 3.5Class 100ISO 5Grade A
Grade BM 3.5Class 100ISO 5Grade B
Grade CM 5.5Class 10000ISO 7Grade C
Grade DM 6.5Class 100000ISO 8Grade D

 

A buffer zone is always controlled by HVAC (Heating, Ventilation, and Air Conditioning) system maintains the positive pressure between (10~20) pascals. Positive pressure prevent the entrance of different types of airborne particle including various types of contaminants. The buffer area must be surrounded by class 10,000(ISO Class 7) or class 100,000(ISO Class 7) otherwise compounding of sterile manufacturing can’t be perform.

This area must be free from any type of unwanted furniture or materials or stationary items. USP <797> Pharmaceutical compounding—sterile preparations- states that a Buffer Room is “An ISO Class 7 or cleaner room with fixed walls and doors where PEC(primary engineering controls) that generate and maintain an ISO Class 5 environment are physically located. The buffer room may only be accessed through the Ante-Room”.

What is Ante-Room?

As per USP the Ante-Room is “An ISO Class 8 or cleaner room with fixed walls and doors where personnel hand hygiene, garbing procedures, and other activities that generate high particulate levels may be performed. The ante-room is the transition room between the unclassified area of the facility and the Buffer Room”.

Buffer Area Requirements

A buffer area must be free from any source of water and therefore drains or sink can’t be present here. To handle emergency situation an eye washer may be present upon proper justification and it should be disinfected and clean properly.

This area need validated in such a way that object that will be use in this area must be present during area qualification and buffer area must be re-qualified if further add any type of machine or device or anything. During area qualification the environmental monitoring must be perform for viable and non-viable particle. Any type of deviation must be addressed and area must be re-qualified. It is the best practice to perform the air quality test of the buffer area and it must be validated in once in every six month and air pattern must be check during validation.

 

Compounding Area ACPH Requirement

Unclassified SCA(Segregated
Compounding Area)
No requirement
ISO Class 7 room(s) ≥30 ACPH
ISO Class 8 room(s) ≥20 ACPH
Air Quality Standards in buffer area

Sterile manufacturing area must be well designed so that the risk of airborne contamination can be decrease. Proper control to be applied in the area and particle generation must be minimize as less as possible. The following table has been depicted from ISO 14644-1, Cleanrooms and associated controlled environments and Limits for number of particles ≥0.5 μm measured in dynamic operating conditions.

ISO Classification of Particulate Matter in Room Air

ISO ClassParticle Count/m3
335.2
4352
53520
635,200
7352,000
83,520,000

 

Buffer area and its importance in sterile manufacturing facility

In a pharmaceutical company’s sterile manufacturing facility, buffer zones play a critical role in maintaining the integrity and quality of the drug product. A buffer zone is an intermediate area between the non-sterile and sterile areas of a facility and serves as a transition point to minimize the risk of contamination. Below are some key aspects of buffer zones and their importance in sterile manufacturing.

List of key aspects
  • Pollution control
  • Transfer of personnel and material
  • Equipment transfer
  • Airflow management
  • Prepare ingredients
  • Documentation and Training
  • Quality Assurance

 

Pollution control

The primary purpose of a buffer zone is to prevent contaminants from entering critical sterile production areas. This includes airborne particles, microorganisms, and other potential contaminants.
A buffer zone typically creates a barrier to pollutants by regulating environmental conditions such as air quality, temperature, and humidity.

The primary purpose of creating buffer zones as part of the sterile manufacturing process is to provide a strong defense against the entry of contaminants into highly sensitive and critical areas where pharmaceutical products are carefully manufactured. These contaminants cover a wide range of threats, from airborne particles to microorganisms to a variety of potential pollutants.

Looking deeper into the details, the buffer zone has been carefully designed to provide stringent security that protects the sterile manufacturing area from external contaminants that could affect the quality and safety of manufactured pharmaceutical products. Environmental conditions within the buffer zone are carefully monitored to implement a comprehensive defense strategy.

For example, air quality is tightly controlled through advanced filtration systems to minimize the risk that airborne particles pose to manufacturing processes. Temperatures are maintained within precise parameters, so any deviations that could negatively impact the sterile area are immediately addressed. Humidity is also carefully monitored and controlled to create an environment in which microorganisms can thrive.

For example, in pharmaceutical facilities producing injectable drugs, buffer zones serve as an important barrier to protect the aseptic filling area from potential contaminants. Air quality is maintained at the highest level with a HEPA (High Efficiency Particulate Air) filter that effectively captures and removes airborne particles. Temperature control devices are in place to ensure that the aseptic filling process takes place within optimal limits and to prevent deviations that could compromise sterility.

Essentially, the buffer zone serves as a carefully controlled environment that takes a multifaceted approach to maintain the integrity of the sterile manufacturing area. This comprehensive strategy not only ensures the quality of our pharmaceutical products, but also complies with stringent regulatory standards for sterile manufacturing processes.

 

Transfer of personnel and material

Personnel and materials entering the sterile production area must pass through a buffer zone. This helps reduce the introduction of contaminants from non-sterile areas to personnel or materials.
Strict donning procedures and hygiene practices are typically implemented in buffer zones to ensure that operators and other personnel do not compromise the sterile environment.

To enter the sterile production area, both personnel and materials must pass through a buffer zone. A key goal of this strategic agreement is to limit the potential flow of contaminants that may be inadvertently transmitted by people or materials originating from sterile areas. Creating this intermediate buffer zone protects the overall integrity of the sterile environment from accidental introduction of contaminants.

Within the buffer zone, we systematically implement and enforce strict dress codes and preventive hygiene practices while working cautiously. These measures are essential to maintain ongoing efforts to preserve environmental purity. For example, workers may be required to wear special sterile gowns, gloves, and other protective equipment before entering the buffer zone. This careful adherence to gowning procedures provides an important barrier and prevents potential contaminants from entering the sterile production area.

Additionally, enforcing strict hygiene practices in buffer zones goes beyond dress codes. This includes a comprehensive cleaning regime that includes careful hand hygiene, shoe hygiene and other necessary precautions. For example, workers may need to wash their hands thoroughly or use disinfectant solutions to remove microorganisms from their hands. These measures strengthen the barrier to contamination and help maintain sterile production areas as controlled, clean environments.

In essence, the buffer zone serves as a critical control point for the movement of personnel and materials into the sterile production area. Their role in reducing the risk of contamination is emphasized by careful implementation of donning procedures and hygiene practices. These measures make the buffer zone an essential safeguard, ensuring the maintenance of a sterile environment with the utmost care and precision.

 
Equipment transfer

Equipment required for sterile production areas is often transported through buffer zones after appropriate cleaning and disinfection. This prevents potential contamination of critical equipment and ensures that required sterilization standards are met.

In sterile manufacturing, essential basic equipment undergoes delicate processing to maintain the clean condition required for a sterile environment. After a thorough cleaning and sterilization process, the equipment is transported through strategically designated buffer zones. This intermediate area serves as an important safeguard and prevents potential contamination that could jeopardize the integrity of critical equipment.

Accurate transfer through the buffer zone is a critical step in maintaining the stringent sterility standards required by the pharmaceutical and biotechnology industries. These practices are necessary to ensure that equipment not only remains uncontaminated but also adheres to the rigorous sterilization protocols applicable to controlled environments.

For example, in pharmaceutical manufacturing facilities, items such as stainless steel containers, tubes, and other manufacturing equipment often undergo rigorous cleaning processes that include autoclaving or other effective sterilization methods. Once considered sterile, the equipment is systematically transported through a buffer zone. This buffer zone serves as a transition space with an air filtration system and controlled environmental conditions to prevent the introduction of particles or microorganisms that could compromise the sterility of the equipment.

This thoughtful approach to equipment transfer significantly reduces the risk of introducing contaminants into sterile production areas. By following these established protocols, the industry ensures the production of pharmaceuticals, biologicals and other essential medical products with the highest standards of quality and safety, which ultimately contributes to patient well-being and medical efficiency.

 

Airflow management

Buffer zones are designed for controlled airflow patterns that prevent airborne contaminants from migrating to the sterilization site. This is achieved by using high-efficiency particulate air (HEPA) filters and maintaining positive pressure in the sterile production area.
The buffer zone is designed to incorporate carefully controlled airflow patterns and is specifically designed to prevent airborne contaminants from entering the sterile area. This complex project is achieved using advanced technologies such as HEPA (High-Efficiency Particulate Air) filters, which play a key role in ensuring that air quality in the buffer zone meets the highest standards.

An example of the most modern air purification technology is the use of HEPA filters. Made from a complex network of fibers, these filters have an exceptional ability to capture and remove microscopic particles, including bacteria, viruses and other contaminants. By incorporating these advanced filtration processes, the buffer zone acts as an important line of defense and strengthens the integrity of the sterile production area against potential airborne threats.

Additionally, maintaining positive pressure in the sterile production area serves as an additional layer of protection. Positive pressure allows air to flow from the clean buffer zone to the sterilization zone, reducing the potential for external contaminants to enter the controlled production environment. This positive pressure technology serves as an active measurement and improves the overall reliability of sterilization conditions required for pharmaceutical, biotechnology, or other sensitive manufacturing processes.

To illustrate, imagine a pharmaceutical factory producing important drugs. A buffer zone equipped with a HEPA filter to maintain positive pressure acts as a shield and protects the sterile area where the actual drug is produced and packaged. This ensures that the final drug product meets stringent quality standards and is free of impurities that could compromise effectiveness and safety.

In essence, incorporating HEPA filters and positive pressure in buffer zones is an example of a sophisticated approach to controlling airborne contamination and plays a critical role in maintaining the integrity of sterile manufacturing environments across all industries.

 

Prepare ingredients

Some sterile manufacturing processes require that materials or solutions be prepared before entering the sterile field. Buffer zones may include dedicated workspace to ensure materials are properly handled and inspected before entering the sterile environment.
Some sterile manufacturing processes require careful preparation of materials or solutions before entering the sterile field. Designated space is provided within the buffer area to facilitate these essential tasks and ensure complete and controlled handling of materials prior to incorporation into the sterile environment. This critical step is critical to maintaining the integrity and sterility of the entire manufacturing process.

During this stage of preparation, the materials undergo rigorous testing and processing to eliminate any possibility of contamination. For example, pharmaceutical manufacturing often requires the production of drug formulations in a sterile environment. The buffer zone serves as a conversion zone where raw materials undergo rigorous cleaning processes to ensure they meet the stringent quality standards required for pharmaceutical products.

Additionally, buffer zones play an important role in preventing cross-contamination between non-sterile and sterile areas. For example, in medical device manufacturing, components must be carefully prepared in a controlled environment to prevent the introduction of contaminants that could compromise the safety and effectiveness of the final product. Dedicated spaces within the buffer zone are strategically designed to maintain the highest level of cleanliness and procedural control, reducing the risk of contamination during material preparation stages.

In essence, careful preparation of materials in the buffer zone is a critical aspect of sterile manufacturing where accuracy and protocol compliance are critical. By establishing a dedicated space for material handling, the industry can ensure the highest quality and purity of materials entering the sterile area, ultimately contributing to the overall success and reliability of the sterile manufacturing process.

 

Documentation and Training

Proper documentation and training of buffer zone staff is important. Standard operating procedures (SOPs) and donning, material movement and equipment handling protocols are strictly followed to maintain high levels of hygiene and minimize risk of contamination.

Careful documentation and thorough training of buffer zone staff are essential. These rigorous procedures aim to maintain the highest hygiene standards and minimize potential risks associated with contamination. Implementation of clearly defined standard operating procedures (SOPs) and protocols is the cornerstone of this strategy and covers essential aspects such as hardening procedures, material movement processes, and equipment management protocols.

For example, for donning procedures, clear guidelines are established that regulate the correct donning and doffing of protective devices. This includes step-by-step instructions for workers on how to don and doff clothing, including details on donning and doffing orders to minimize the risk of introducing contaminants.

The material movement process is another important aspect where the SOPs outline the precautions involved in moving materials within the buffer zone. This includes not only physical transfer, but also documentation and verification procedures to ensure proper traceability and prevent inadvertent introduction of contaminants during transfer.

Equipment management protocols help maintain a clean environment in the buffer zone. SOPs reduce the likelihood that equipment will become a potential source of contamination by describing the correct procedures for operating and maintaining equipment. This may include regular cleaning schedules, routine maintenance checks, and special equipment handling procedures to prevent damage to facility cleanliness.

Continuing training programs also play an important role in ensuring that employees not only know these procedures but are also able to perform them. Training sessions simulate real-life situations, provide experience and enable employees to respond effectively to unexpected situations. This proactive approach helps promote a culture of awareness, accountability and accuracy among employees and highlights the importance of their role in maintaining the integrity of the buffer zone.

By combining detailed documentation with an in-depth training plan, companies can create resilient structures that minimize the risk of contamination in the buffer zone. This commitment to excellent procedural compliance ultimately contributes to the overall success of maintaining a healthy, controlled environment critical to the processes conducted in the buffer zone.

 

Quality Assurance

The buffer zone is subject to strict control and quality assurance measures to ensure compliance with regulatory requirements and internal quality standards. Regular environmental checks, air particle counts and microbial testing are frequently performed in these areas.

In summary, buffer zones are an important component of the overall contamination control strategy of a sterile manufacturing facility. Maintains the integrity of the sterile environment and ensures safe, high-quality pharmaceutical production by effectively managing the movement of people, materials, and equipment.

Buffer zones are subject to careful inspection and rigorous monitoring protocols and quality assurance systems to ensure compliance with both regulatory requirements and internal quality standards. Rigorous procedures, including regular environmental monitoring, air particle counting and microbial testing, are regularly implemented in these areas to maintain the highest standards of cleanliness and sterility.

For example, environmental monitoring involves continuous assessment of factors such as temperature, humidity, and airborne particles. This ensures that the optimal conditions required for the sterile production process always exist in the buffer area. On the other hand, air particle counting is the systematic measurement and analysis of fine dust particles present in the air to prevent potential pollution risks.

Microbiological testing represents another important aspect of the buffer zone monitoring process. Tests surfaces, air, and devices for the presence of microorganisms. By proactively identifying and containing microbial threats, facilities can proactively maintain the integrity of their sterile environment.

In essence, buffer zones play a central role in the complete contamination control strategy of a sterile manufacturing facility. It serves as a hub for producing medicines of the highest quality and safety. By effectively managing the movement of people, materials and equipment, buffer zones play a critical role in maintaining the rigorous standards required for pharmaceutical manufacturing. This careful approach prevents potential contamination and contributes to the overall success of the manufacturing process and the reliability of the drug produced.

Buffer area and its importance in sterile manufacturing facility Read More »

What do you mean by Reverse Osmosis System?

Reverse Osmosis (RO)

Reverse osmosis is a well-known Water Purification Technology that uses semi-permeable or partially permeable membranes to selectively separate unwanted molecules, large particles and ions from drinking water. This method uses pressure to overcome the inherent osmotic pressure of the process fluid.

In industry, the reverse osmosis process has become very popular due to its effectiveness in removing impurities and producing high quality water. The importance of this technology extends to the production of drinking water that can retain most of the suspended chemicals and solutes present in the water source.

To illustrate, imagine an industrial environment where reverse osmosis is used to treat water in manufacturing processes. In these situations, the semi-permeable membrane acts as a barrier and prevents the passage of contaminants such as minerals, bacteria, and other unwanted substances. The applied pressure acts as a driving force, effectively pushing water through the membrane and leaving contaminants aside.

When it comes to drinking water production, municipalities often use reverse osmosis systems to ensure that the water supplied to homes meets strict quality standards. Through this process, contaminants are separated, and the resulting liquid on the other side of the membrane is pure and safe to consume.

Fundamentally, the advantage of reverse osmosis lies in its ability to selectively separate components based on their size and molecular properties, making it a versatile and widely used method for water purification in both industrial and domestic applications. Residual solutes remain on one side of the membrane and pure liquid remains on the other side. This demonstrates the simple yet powerful results of this purification process.

The particle down to 0.0001 micron can easily pass through the semipermeable membrane. This membrane also retain Bacteria due to its cells range about 1 to 10 microns in length and from 0.2 to 1 micron in width but water can pass freely which molecular size is 0.000282 micron.

 

Why Called Reverse Osmosis?

In osmosis, the intrinsic tendency of solutes to flow spontaneously from an area of low solute concentration to an area of high solute concentration is facilitated by a semipermeable membrane. The area with low solute concentration is called the high water potential area, and the area with high solute concentration is called the low water potential area.

To investigate this process in more detail, let us consider a real example using cell membranes. Imagine a plant cell in solution. When the solute concentration in the external environment is lower than the concentration inside the cell, water naturally enters the cell by osmosis. This flow of water helps maintain turgor pressure and keep the cells rigid. In this situation, the extracellular solution is associated with a high water potential, whereas the cell interior is associated with a low water potential.

Now let’s look at reverse osmosis (RO), a practical application of this principle. In situations where water needs to be purified for human consumption or industrial processes, reverse osmosis is used. Here, excessive pressure is applied to force water molecules to pass through a semi-permeable membrane with a high solute concentration (a source of impure water). This process effectively reverses the natural flow of solvent, allowing only pure water molecules to pass through and retaining dissolved contaminants. Reverse osmosis is often used in desalination plants, where seawater is separated from salt and other contaminants and converted into fresh water.

Osmosis is a fundamental biological and physical process, and its practical application in reverse osmosis has important implications for water purification and various industrial processes. Understanding the dynamics of water potential and solute transport can provide valuable insights into these natural and engineered systems.

 

Use of Reverse Osmosis

Mainly water treatment or conditioning purpose in chemical, pharmaceutical, mechanical industries use Reverse Osmosis System. This process is largely used in water treatment industry as water purification process.

Difference between Osmosis and Reverse Osmosis

OsmosisReverse Osmosis
This is the natural process where the solute molecules are passed through a partial membrane from area of lower concentration to higher concentration.This is the artificial process where the solute molecules are passed through a partial membrane from area of higher concentration to lower concentration upon applied mechanical pressure.
Osmosis is a natural process.Reverse Osmosis is an artificial process.
It Occurs along the potential gradient.It Occurs against the potential gradient.
This is observed during welling of resins and other seeds when they are soaked in water.This is observed during welling of resins and other seeds when they are soaked in water. Widely is used in water purification systems.

 

Advantage of Reverse Osmosis
  • Reverse osmosis system require less energy consumption due to this system doesn’t allow phase change/separation.
  • This system is very much space saving as its very compacted compare to most of the water purification system.
  • This a simple standard equipped process so any new comer labor can easily read it.
  • The modern reverse osmosis system is totally automated and this is readily shutdown upon interlock system so labor cost is very much low.
  • Most of the modern RO system able scheduled maintenance without shutdown of the full plant.
  • If anyone want to expand the RO plant; this readily possible without changing the whole RO plant.
  • This the most effective form of water purification process and going to popular in day by day.
  • Best option for naval ship to make desalination of water to give fresh water to the crew.
  • Printing industry use RO system to increase the water quality for different printing purpose.

Disadvantages of Reverse Osmosis
  • RO system can’t be use in high concentration solutions.
  • This is very much sophisticated which is susceptible to fouling so this system can’t be use without pretreatment.
  • Membrane and material of construction must be compatible with the RO feed streams otherwise membrane must be consider.
  • The great problem of RO system is that it removes most of the minerals from the feed water and deliver the acidic water. Another big problem is about 20 gallon water must be waste to make 1 Gallon RO treated water.
  • RO system is very time much time consuming, it requires near about three hour to make one gallon of water. This means you have to wait all day long to have sufficient water availability at home. This system is not only time consuming but also costly.

How does Reverse Osmosis work?

The operation of a conventional reverse osmosis (RO) system is elegant and simple. Basically, a typical RO system consists of a pump and a semi-permeable membrane. The purpose of the pump is to draw feedwater through a semipermeable membrane and create a flow that promotes the separation of the solutes. The pressure generated by the pump varies from low to high depending on the solute concentration of the feed water. If the feed water contains a large amount of solute, a correspondingly high pressure is required to force it through the semipermeable membrane.

As soon as the feed water is exposed to this pressure and passes through the semi-permeable RO membrane, it is transformed and becomes the so-called permeate water. Conversely, water that leaves the system without passing through the membrane is called wastewater flow.

In standard operation of a semipermeable RO membrane, impressive solute retention rates are achieved, of which more than 95% is sent to the waste stream. These high levels of solutes are an important aspect of the RO process. Although it retains most of the solutes, the semi-permeable membrane allows water molecules to pass through effectively, ensuring that the incoming water is separated from the pure, concentrated solution.

To illustrate, imagine a scenario where the water supply contains significant concentrations of contaminants. In these cases, the pump in the RO system applies significant pressure to force water through the semipermeable membrane. The membrane selectively blocks dissolved substances and allows only pure water to pass through. This efficient separation process ensures the production of clean, pure water, making reverse osmosis a widely used technology in a variety of industries, including water treatment and desalination processes.

Which material didn’t remove by Reverse osmosis?

During reverse Osmosis process a wide range of contaminants such as Asbestos, Salts, Lead, Mercury, Calcium and Iron reduce in significant amount so that a fresh water can produce but it can’t remove the following items-

  • Some Pesticide
  • Solvents
  • Volatile Organic Chemicals
  • Metals and Ions such as Radon and Chlorine
  • Organic Chemicals such as 2,4-D and 1,2,4-trichlorobenzene, Atrazine, Benzene, Carbon tetrachloride, Dichlorobenzene, Trihalomethanes (THMs) and Toluene

Is it safe to consume reverse osmosis water on a daily basis?

Of course, regular consumption of reverse osmosis water (RO water) is generally considered safe. Reverse osmosis, a water purification method, uses a semi-permeable membrane to remove impurities and contaminants from water. By pressurizing water and forcing it through this membrane, substances such as minerals, bacteria, and certain chemicals are effectively filtered out, creating pure water.

RO water has proven to be a reliable choice for everyday use, especially for those seeking to remove a wide range of contaminants from their drinking water. Despite its purifying properties, reverse osmosis water may still contain some essential minerals that are beneficial to your overall health. To address this issue, some people choose to supplement their mineral intake by adding dietary supplements or mineral supplements to ensure they are getting the nutrients they need.

For example, people who rely heavily on reverse osmosis water can compensate for potential mineral deficiencies by including a variety of nutrient-dense foods, such as vegetables, nuts, and seeds, in their diet. Some people may also choose mineral-fortified water or supplements and take a proactive approach to maintaining a balanced mineral intake.

It is important to remember that individual health care needs may vary. If you have a specific health problem or condition, it is recommended that you consult your doctor or nutritionist. A professional consultation can make recommendations based on your individual needs and help you choose the appropriate water source and diet to meet your specific health goals.

 

Does reverse osmosis water surpass the quality of bottled water?

Reverse Osmosis treated water remove more than 95% of impurities of feed water and their cost is actually a fraction to bottled water within a years’ time period. So taking a bottled water you have confirm about minerals content of its existing label.

Reverse osmosis (RO) water and bottled water can both be of high quality, but the comparison depends on various factors, including the source of the bottled water and the specific RO system in question. Let’s break down some key points:

Source of Bottled Water:

If the bottled water comes from a natural, clean source, it may already be of high quality without the need for additional purification. However, some bottled water is sourced from municipal supplies, and the purification methods can vary.

Reverse Osmosis Water:

RO is an effective water purification process that uses a semi-permeable membrane to remove contaminants and impurities. RO systems can eliminate a wide range of impurities, including minerals, chemicals, and microorganisms. The quality of RO water depends on the efficiency of the RO system and the maintenance of the filters.

Taste and Mineral Content

Some people prefer the taste of water with certain minerals, which may be present in varying amounts in different bottled waters. RO water tends to be demineralized, as the process removes minerals along with other impurities. Some people find this taste flat and may choose to remineralize the water.

Convenience and Environmental Impact

Bottled water is convenient but can generate plastic waste, contributing to environmental concerns. RO systems provide a more sustainable and cost-effective solution in the long run, as they require less single-use plastic.

Regulations and Standards

Both bottled water and RO systems are subject to regulatory standards, but the stringency can vary by region. It’s essential to ensure that the RO system is properly maintained and meets relevant water quality standards.

In summary, the quality of RO water can surpass that of some bottled waters, especially if the latter is sourced from questionable supplies. However, the comparison is nuanced and depends on individual preferences, the source of bottled water, and the effectiveness of the RO system. Ultimately, both options can provide high-quality drinking water, but factors like taste, convenience, and environmental impact may influence the choice between them.

 

WHO Guidelines for drinking water

Serial No. Materials Name Content Name
1Iron 0.3 mg/L
2Zinc 3.0 mg/L
3Copper 2.0 mg/L
4Iodine Nil
5Calcium Nil
6Phosphorus Nil
7Magnesium Nil
8Fluoride 1.5 mg/L
9Sodium 200 mg/L
10Potassium Nil
11Chloride 250 mg/L

Which is healthier: Distilled or Reverse Osmosis water?

Both systems are used for water purification and each is tailored to specific requirements. Distillation processes are widely used in industries such as the pharmaceutical industry where the need for high purity water that meets stringent specifications is paramount. In this method, water is exposed to high temperatures and changes into a vapor phase. The steam is then cooled to obtain pure water. This process is very efficient and removes all dissolved substances, including minerals such as calcium and magnesium.

In contrast, reverse osmosis (RO) is a water purification technology that creates pure water by removing various impurities using a semi-permeable membrane. Additionally, minerals are added to improve water quality and preserve its original taste.

For those looking for ultra-pure water, distilled water is the perfect choice. However, to prevent mineral deficiencies, it is important to supplement your diet with mineral-rich foods.

When you choose reverse osmosis water, you get pure water with added mineral content. This makes RO water an ideal choice over distilled water, which can remove important minerals and remove up to 99.99% of the solutes in tap water. Choosing reverse osmosis water not only meets your hydration needs, it also alleviates concerns related to mineral deficiencies, making it a preferred choice for your overall health.

Is reverse osmosis water healthy?

There is no documented evidence that Reverse Osmosis water is harmful to public health issue. If a normal health person take balanced diet regularly then he or she will not suffer any type of gastrointestinal problem. So drinking of RO water is not harmful to your health though RO system remove some minerals during its mechanical process.

Is Reverse Osmosis kill Bacteria?

There are currently thousands of reverse osmosis (RO) systems on the market worldwide, and consumers are happy to use this technology to protect their families from harmful chemicals and pollutants such as lead, arsenic, pesticides, chlorine, and more. Various total dissolved solids (TDS). These consumers firmly believe that their newly purchased reverse osmosis system has the ability to remove all bacteria present in their drinking water. But a disappointing reality is emerging. Contrary to popular belief, reverse osmosis systems are not designed to remove bacteria. Instead, the reservoirs in these systems unintentionally serve as breeding grounds for bacterial growth.

Recent medical studies have revealed the alarming effects of exposure to bacteria-contaminated RO tanks in immunocompromised individuals, including infants, children with autism, and elderly patients. This health condition is scientifically known as heterotrophic plate counting (HPC), a method of measuring colony forming bacteria (heterotrophic bacteria) in drinking water. Removing these bacteria from drinking water has proven to be an almost insurmountable challenge.

Taking these difficult situations into account, practical solutions emerge. Many people choose to incorporate ultraviolet (UV) light immediately after their RO system to neutralize bacteria. It is important to note that UV light does not kill bacteria, but rather disinfects them, preventing them from growing further. This innovative approach is especially essential considering vulnerable populations at risk of health problems due to exposure to bacteria.

However, there are important caveats when considering placing UV lights behind an RO system, especially behind the kitchen sink. This method may not be optimal because UV rays have the unintended consequence of heating the water. As a result, the RO water delivered from the tap becomes hot, affecting the user experience and potentially reducing the efficiency of the overall water treatment process.

To address these complexities, users must recognize the limitations of RO systems and make good use of complementary technologies, such as UV light, to improve water safety. As we explore water treatment technologies, a concise, informed approach is essential to ensure the health and well-being of individuals and families around the world.

How RO System kill Bacteria?

Current trends indicate that modern RO systems typically only have a carbon filter directly in front of the water discharge tank. This setup effectively removes many tastes and odors, but inadvertently creates an ideal environment for many types of bacteria to grow. Recently, “Disinfectant Cartridges” have introduced an innovative system that actively removes electrons from all microorganisms. These innovative cartridges can be used with carbon filters, providing a complete solution to remove 99.99% to 99.999% of bacteria from water.

Reverse osmosis (RO) systems are generally effective at removing bacteria because they pass water through a semi-permeable membrane that blocks particles containing bacteria. However, it is very important to properly maintain your RO system to ensure continued performance and prevent bacterial growth. Here are some steps to eliminate bacteria and maintain a clean RO system:

Regular maintenance

Follow the manufacturer’s recommendations for regular maintenance. This often involves replacing filters and membranes at specified intervals.
Check and replace pre- and post-filters according to manufacturer recommendations.

Sterilization

Disinfect your RO system regularly to remove bacteria and prevent biofilm formation.
Use an appropriate disinfectant solution recommended by the RO system manufacturer. Commonly used solutions include hydrogen peroxide or chlorine-based disinfectants.
Follow the manufacturer’s instructions for the sterilization process, including appropriate dilution and contact time.

Flush the system

Flush your RO system regularly to remove accumulated debris and bacteria.
Follow the manufacturer’s instructions for cleaning the system, as the process may vary depending on your RO unit.

Maintain a clean environment

Make sure the area around the RO system is clean and free of contaminants.
Prevent contaminants from entering the system during maintenance or filter replacement.

Water quality monitoring

Check the water quality in your RO system regularly to ensure it meets desired standards.
If bacterial contamination is suspected, conduct a water quality test for each bacteria and take appropriate action based on the results.

Replace existing components

Replace damaged or worn components immediately, as damaged parts can compromise the integrity of the system and provide an opportunity for bacterial growth.

Temperature control

Maintain water temperature within the recommended range for your RO system. Warm temperatures can encourage bacterial growth.

Professional service

If you are unsure about maintenance or suspect bacterial contamination, you should contact a professional service technician or the manufacturer for assistance.

Always follow the manufacturer’s instructions and recommendations for your specific reverse osmosis system, as maintenance procedures may vary depending on the model. Regular and proper maintenance is important to ensure the performance and longevity of your RO system and prevent bacteria.

What are the components of a Reverse Osmosis System?

List of components for Reverse Osmosis System
  • Pressure Vessels & Membranes
  • Reverse Osmosis Slide
  • Cartridge Filter
  • High Pressure Pump
  • Control Panel
  • Reverse Osmosis Maintenance
  • Replace Reverse Osmosis Filters on Schedule

Pressure Vessels & Membranes

You can’t think a Reverse Osmosis System without membranes. The membranes that makes the reverse Osmosis System vary based on the type of water you are deal with. A typical municipal grade water is far difference with hospital grade disinfection water. A membranes is the vital part of the RO system which removes the all types of contaminants, pesticides, dirt, and various types of impurities. Call an expert before selecting the membrane based on your demand. A typical RO system contains more than 100 membranes and size of the

Membrane vary from two and half inch to eight inch and more.

Reverse Osmosis Slide

Make your RO System more durable by the help of the carbon steel frame where you can mount all of the component of your Reverse Osmosis systems. This type of frame need to be more supportive as it have to act against vibration of the RO pumps and it is better to mount the RO system to the ground base for better performance.

Cartridge Filter

Most of the recent RO system comes up with cartridge filter to prevent particle to hit directly to the membrane. Actually cartridge help the membrane filter to damage itself. This cartridge filter made of five micron spun polypropylene and this can be expand if required. It is design in such a way that it can withhold the sufficient filter come from feed water pump.

High Pressure Pump

Most of the commercial and industrial settings use high grade pump so that the rejection rate from the Reverse Osmosis System comes out as vital. This is very much desirable that the quality of the membrane must be match the horse power of the high pressure pump so that a better match develop for the suitable system.

Control Panel

A RO system is always comes up with advance PLCs or solid state microprocessor depending control systems how advance level control systems you demand. The control system can be use the multiple system at time like cleaning, chemical dosing, pretreatment and other component also. You can use another component with this system if you want.

Reverse Osmosis Maintenance

 A Reverse Osmosis system last more than 10 years if it properly maintained. If you want to last your Reverse Osmosis system then you have to maintain your system regularly. Here is the best way to maintained your favorite RO system

Replace Reverse Osmosis Filters on Schedule

Generally you will find the information at the RO system manual, please read carefully the instructions  where your RO system contains three to five stages filter and each filter has replacement due date. A modern RO membrane need to change every two years. RO system replacement kid always available at the current market.

You may not replace the RO membrane so before buy check filter with RO membrane and filter without RO membrane which is your requirement.

 

Different type of RO Filter and their longevity

List of RO Filters
  • Sediment Filter
  • Carbon Filter
  • Reverse Osmosis Membrane
  • Polishing (GAC) Filter

 

Sediment Filter

Actually the sediment filter is designed to protect membrane filter and this filter remove all type of sediment, strain, dirt and silt and this filter need to remove every 12 month. This filter protect the membrane filter from various type of dissolved solute so that the membrane filter longevity increase. As the membrane is most costly than sediment filter so to protect the membrane filter you have to change the sediment filter in every 12 months to run the system without any significant harm.

Carbon Filter

There are two types of carbon filter include in modern RO system which are carbon block filter and granular activated carbon (GAC) filter. This type of carbon filter actually designed to filter the various types of contaminants, lead, pesticides and chlorine. Both of the carbon filter possess high adsorption power. The filters to be replace within 6-12 months. The longevity of carbon filter depends on how much dirty water you are deal with. If you are deal with high dirty water your filter will be block within short period of time.

Reverse Osmosis Membrane

The RO semipermeable membrane  design to allow water but it will filter out all types of contaminant. If timely replace the carbon filter and sediment filter in every years or timely manner then your membrane filter longevity will increase almost two years.

Polishing (GAC) Filter

A modern RO system the final filter polish the water to perform the final stage cleaning of the water remove remaining odor and taste. The Granular Activated Filter (GAC) ensure that you are deal with the outstanding drinking water.

If fail to replace the filter in time then  then this system damage the whole system and your water flow may decrease gradually in to the faucet. When you observe the water flow is decreasing then this the best time to change the filter.

All the filter in RO system to be change within 6-12 months except RO membrane filter and this membrane filter to be change within 2 years.

 

RO System Maintenance Checklist

A reverse osmosis system to be sanitize and recharge annually. Call a local expert to perform the job accordingly otherwise you have to confirm that are able to do the same.

If you think you can do it, then you have to read the RO system manual clearly about sanitization of the RO system then do the same

How to Clean and Sanitize Your System Annually
  • Check all the packages of the filters are new and ready for use.
  • All the area is clean and fit service of the RO system
  • Remove all the excess dirt and dust.
  • Firstly wash your hand soap the wear a sanitary gloves
  • Shut down the main valve
  • Clear all water from RO faucet
  • Remove Carbon Filter and sediment filter from its housing
  • Then remove the RO membrane from its housing
  • In stage one housing pour one cup of Hydrogen Peroxide
  • Attain attach the all connections
  • Turn the main valve
  • Run the system and this will fill rapidly as no filter attached here
  • In this condition run at least to cycle
  • Shutdown the main valve again
  • Now install the main brand new filter
  • Fill the tank and drain out more than two times
  • Now your system is ready to use and repeat this process in every one year

Can Reverse Osmosis System handle Hard Water?

If you have very hard water, consider using a whole house water softener before using a reverse osmosis system. Magnesium and calcium cause water hardness and these elements can cause RO systems to become clogged. First, a water softener is installed to treat the water before it reaches the RO system.

In areas where water hardness is a concern, it is essential to comprehensively address this issue by installing a whole home water softener. The main causes of water hardness are magnesium and calcium ions. When these ions are present in high concentrations, they can be problematic for existing water treatment systems such as reverse osmosis (RO). The inherent limitations of RO systems in effectively processing minerals that produce this hardness can lead to clogging problems and reduce the overall efficiency and lifespan of the RO system.

To illustrate, let us consider a real situation where a household in an area with high water hardness does not pre-treat with a water softener and relies solely on an RO system. Magnesium and calcium ions in untreated water tend to accumulate on the RO membrane, gradually forming scale deposits. Over time, these deposits interfere with the filtration process, reducing water flow, increasing energy consumption, and increasing RO system maintenance.

One strategic approach to alleviate these problems and ensure optimal performance is to install a water softener upstream of the RO system in the water treatment sequence. Water softeners effectively reduce the concentration of magnesium and calcium ions, preventing them from building up in the reverse osmosis system. By implementing this two-step treatment process, the water is first softened to eliminate hardness issues and then sent to the RO system for further purification.

In summary, integrating a whole house water softener in front of a reverse osmosis system has proven to be a practical and efficient solution in areas with higher water hardness. This method not only ensures RO system performance, but also improves overall water quality by addressing specific mineral content issues early in the treatment process.

What do you mean by Reverse Osmosis System? Read More »

What is the difference between Pure Water and Potable Water?

Difference between Pure Water and Potable Water

To comprehend the Difference between Pure Water and Potable Water, it is essential to examine the following statement. Only then can we grasp the fundamental Difference between Pure Water and Potable Water.

 

Pure Water

The water that has been mechanically filtered or processed and removed the unwanted impurities to make it more suitable or palatable for use is called pure water. Previously, the common form of pure water was distilled water but now a days water has been purified in several process including distillation such as

  • Boiling
  • Carbon Filtering
  • Clay Vessel Filtration
  • Co-Current Deionization
  • Counter-Current Deionization
  • Deionization
  • Demineralization
  • Desalination
  • Double Distillation
  • Electrodeionization(EDI)
  • Iodine Addition
  • Microfiltration
  • Mixed Bed Deionization
  • Ultraviolet Oxidation
  • Ultrafiltration
  • Reverse Osmosis
  • Solar Purification
  • Chlorination

To increase the quality of the water, several process are applied to make it ultrapure so that a trace amount of impurities or contaminants are present which is readily acceptable and it does not cause any harm to end user. When a water declared ultrapure water then the contaminants are present as parts per million (ppm) or parts per billion (ppb) or parts per trillion (ppt).

Generally pure water produced from largely in ground water or drinking water. To make pure water following impurities need to remove-

  • Various type Organic compounds
  • Inorganic ions
  • Different types of Bacteria
  • Endotoxins
  • Particulates
  • Gases
Uses of Pure Water

Pure water widely use in Pharmaceuticals industry as

  • Raw material
  • Solvent
  • Liquid Preparation
  • Analytical Reagents
  • Formulation
  • API[Active Pharmaceutical Ingredient]

Mostly the microbiological limit is the vital point of use of pure water in pharmaceutical industry and it must be regularly monitored to control the microbial contamination.

Pure water also use in

  • Commercial Beverage Industry
  • Different Laboratory
  • Cooking
  • Drinking

In semiconductor industry; pure water is use as primary feed water then in turn to ultrapure water. The most common use of pure water in pharmaceutical industry is to make Water For Injection[WFI] where pure water is undergone some distillation process to maintain its microbial tight limit as 10 cfu per 100 ml where USP limit 100 cfu[colony-forming unit] per ml. Deionized or distilled water commonly used in Lead-Acid Battery Company which later use in various types of Trucks and Car. Using of tap water reduce the lifetime of batteries as it contains ions so deionized water is use in car or truck battery to increase its shelf life.

Deionized water also used in cosmetics and some country consider “Aqua” must be present with its brand name in its label as it’s the standard name of water. Distilled water use in Laser marking system and PC Water Cooling System which prevents to store bacteria and different types of algae. As the dissolved solute didn’t present in pure water so using of pure water in car washing, window cleaning and other application where need such type of application didn’t leave any type of spots. Another use of deionized water is water-fog fire-extinguishing systems which is designed for electrical equipment used.

 

Pure Water Health Effects

Mechanical process of making distilled water removes all type of mineral from pure water and another process like nanofiltration and reverse osmosis [RO] remove most of the mineral from pure water. So the benefit of pure water when use in drinking water is ultimate not healthier compare to conventional drinking water.

In 1980, WHO [World Health Organization] reveals an experiment report that drinking demineralized water cause diuresis. When most of the mineral like Calcium, Magnesium, Potassium, Sodium, Bicarbonate, Iron, and zinc remove from pure water by demineralization process cause deficiency of essential minerals. Recommended concentration of different minerals in water as

Magnesium of pure water
  • Minimum Concentration: 10 mg/L
  • Maximum Concentration: 20~30 mg/L
Calcium of pure water
  • Minimum Concentration: 20 mg/L
  • Maximum Concentration: 40~80 mg/L

Total water hardness [Addition of Calcium & Magnesium]: 2~4 mmol/L. When hardness reach above 5 mmol/L then incidences of urinary stones, gallstones, kidney stones, arthropathies and arthrosis probability arise and observed in most of the cases. A healthy dental health recommended 0.5–1.0 mg/L fluoride in water where the guideline describe 1.5 mg/L to avoid potential dental fluorosis.

Water filtration devices are becoming more popular and become the part and parcel of the modern life but the real fact is this type of machine didn’t perform any type of distillation at all though they are calming distillation process; actually they use Reverse osmosis process to pure the water and being sold all around the globe.

Generally a Municipal grade water contains trace or low level of impurities or contaminants but it is save for day to day use. Actually Reverse osmosis and distillation process remove more than 70,000 chemical compounds from water though they present in low level in water to create potential hazard.

Pure water to be replace with drinking water as it didn’t contains calcium which play a vital role in biological system in our body and its found normally in potable water. So lack of natural occurring minerals, pure water is not suitable to drinking for better health issue. Most of the expert encourage people to take water contains natural occurring minerals which is more beneficial for sound health. Check the mineral content before taking any type of water especially in bottled.

 

Potable Water

Frequently known as “Drinking Water” which is very much essential for day to day intake on our daily needs based on demands for their chemical composition. The quantity of drinking water varies based on working environment. People working hot climate need large amount of potable water, upto 15Liters. Tap water needs to meet potable water quality though a small amount is used in food preparation and large amount use in irrigation, toilets and washing purpose.

Now more than 89% people are able to get potential source of potable water which can be readily use but in some region of Africa still crisis in potable water depend on public taps or wells.

Potable Water Resources

More than two third earth surface covers by water but most of them are actually saline and  only a small amount can use. Access of potable water is expensive and the supply system is not always suitable.

Main source of potable water

  • Rivers
  • Different Water supplies network
  • Ground water
  • Spring
  • Rain
  • Hail
  • Snow
  • Fog
  • Streams
  • Sea Water
  • Generated Water

A healthy man require more than 3.7Liters water and female require 2.7 liters water per day and this quantity may varies based on physical activities.

Potable Water Quality

As per WHO [World Health Organization] declare that “safe drinking-water is water that “does not represent any significant risk to health over a lifetime of consumption, including different sensitivities that may occur between life stages”

The critical parameter for drinking water is

  • Physical
  • Chemical
  • Microbiological

Main Physical and chemical parameters are

  • Heavy metals
  • Total suspended solids (TSS)
  • Trace organic compounds
  • Turbidity

Main Microbiological parameters are

  • Coliform Bacteria
  • E. Coli
  • Specific Pathogens

Specific Pathogens include

  • Vibrio cholerae
  • Viruses
  • Protozoan parasites

Presence of different chemical substances tend to more chronic health risk such as arsenic can create more potent impact same as nitrates/nitrites can create more impact. Microbial pathogens are more concern about contaminations due to it’s create more immediate effect and potential health consequences. The widely contamination source of water is human sewerage which contains faecal pathogens and parasites and more than one million people death in every year around the globe due to water born diseases.

Treatment of Potable Water

Most the Potable water need to treat before use depend on the source. The most widely used treatment process is boiling of potable water. But it’s require more fuel and time consuming also and another problem is storage of boiling potable water is difficult to maintain it sterile condition.

The best technique for potable water treatment is chemical disinfection filtration, and exposure to ultraviolet radiation and another method is desalinization which is widely used in dry area where large amount of saltwater available.

Use of Potable Water

Potable water is widely used. Some of main use of potable water is

  • Bathing
  • Cleaning of machineries
  • Cooking
  • Car Washing
  • Cleaning dishes
  • Drinking
  • Generation of hydroelectricity
  • Hotel and restaurants dishwashing
  • Maintaining osmotic rate in humans
  • Watering plants
  • Washing of different type clothes
Why do we consume Potable Water instead of Pure Water?

The term “Potable Water” refers to water that has undergone special treatment processes to meet established quality standards and regulations to ensure that it is safe for human consumption. Potable Water is carefully treated to remove harmful contaminants and pathogens using methods such as filtration, chlorination, and desalination.

In comparison, the term “Pure Water” generally refers to water that has undergone an extensive distillation or purification process to remove most impurities and achieve an exceptionally high level of purity. While this may seem ideal for cleaning, relying solely on plain water for regular consumption can be uncomfortable and potentially harmful to your health.

It is important to recognize that water in its natural state contains minerals and ions that are essential to human well-being. These ingredients not only contribute to the taste of water, but they also play an important role in maintaining the balance of the body’s internal environment. Drinking Pure Water without these essential minerals for long periods of time can cause mineral deficiencies.

Potable Water is important to maintain harmonious balance. Processes such as filtration, chlorination, and other purification techniques allow Potable Water to remove harmful contaminants while retaining essential minerals. This balance not only makes Potable Water safe for human consumption, but also contributes positively to overall health.

Potable Water also undergoes rigorous testing and treatment protocols to ensure it meets quality standards set by health and environmental authorities. This comprehensive approach ensures that water not only meets safety requirements but also complies with guidelines that promote both human well-being and environmental sustainability. Potable Water has proven to be a practical, health-conscious choice that embodies a thoughtful compromise between cleanliness and preservation of minerals essential for optimal health.

Potable Water also undergoes rigorous testing and treatment protocols to ensure it meets quality standards set by health and environmental authorities. This comprehensive approach ensures that water not only meets safety requirements but also complies with guidelines that promote both human well-being and environmental sustainability. In essence, Potable Water has proven to be a practical, health-conscious choice that embodies a thoughtful compromise between cleanliness and preservation of minerals essential for optimal health.

Potable Water acts as an important storehouse of essential minerals that are important for our body’s health and contains important elements such as calcium and magnesium. Calcium, a key element, plays a fundamental role in a variety of physiological systems. For example, it shows a variety of importance by contributing to bone health, nerve transmission, and muscle function.

Fluoride, another mineral found in drinking water, also plays an important role in maintaining dental health. Found in tooth enamel, it helps prevent cavities and improve overall oral hygiene. By emphasizing the importance of fluoride in water sources, we emphasize the preventive aspect of dental care.

Deficiency of these various minerals can lead to a variety of health problems, including bladder stones, gallstones, kidney stones, arthropathy, and osteoarthritis. For example, calcium deficiency can contribute to the development of kidney stones, highlighting the complex link between mineral intake and preventing certain health conditions.

Having the highest quality Potable Water is essential to activate and optimize your physiological systems. This highlights the importance of not only plain water, but also water that meets the required standards for mineral content, ensuring that your body receives the nutrients it needs to function optimally. Therefore, wise use of water considering its mineral content is essential to promote overall health and prevent mineral deficiencies that can lead to a variety of health complications.

This is all about the Difference between Pure Water and Potable Water.

What is the difference between Pure Water and Potable Water? Read More »

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