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
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.
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.
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.
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-
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.
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.
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.
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.
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 XYZPharma 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.
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.
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
Only released (green tag) materials are brought to the dispensing area.
The dispensing area is completely free from materials of other products.
Correct quantity and approved qualities of materials are being dispensed as per requisition.
Materials that expired first are being dispensed first i.e. to follow FIFO.
Documentation of dispensing
Finished Product Area
Finished products are also stored here for delivery.
Warehouse deliver the finished products as per asked by the planning department.
Rejected Area
If the materials fail to pass QC test, QA give rejected tag (red tag) on each and individual container or box.
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:
They should be accurate and uniform in weight.
The drugs should be uniformly distributed throughout the tablet.
The size and shape should be reasonable for easy administration.
The tablet should not be too hard that they may not disintegrate in the stomach.
They should be chemically and physically stable during storage.
They should not break during transportation or crumble in the hand of the patient.
There should not be any manufacturing defects like cracking, chipping or discoloration.
After disintegration they should be readily dissolved.
They should be easy and economical in production
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
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
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:
DRY GRANULATION
This method is used for powders, which require granulation and sensitive to moisture and water.
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-
Compression of previously made granules
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:
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:
Reducing the percentage of fine in the granulation.
Maintaining desired moisture level in the granulation.
Adjusting the speed and compression force.
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:
Proper designing of punches.
Chrome plating punch surface.
Adequate drying of granules.
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:
Using a dye that can mask of all ingredients.
Using the alternate solvent system for the granulation.
Reducing the drying temperature of the granules.
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:
Using granules of uniform particle size distribution.
Decreasing the fine.
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:
Pellet filling process
Powder filling process
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.
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
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 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
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
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 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.
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.
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.
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
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
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.
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.
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.
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-
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.
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.
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.
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.
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.
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.
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.
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:
Check the blower housing and drain for the possible condensate
Check smooth operation of the blower
Clean locking bolt using grease
Check the Heat Exchanger
Inspect All Screw Connection In-Process Piping System
Maintenance Interval: 6 Monthly
Maintenance Task:
Check all O-Ring and adjustment if it is necessary
Check the filter elements aimed at contamination
Exchange filter elements, if there is any perceptible damage
Maintenance Interval: Yearly
Maintenance Task:
Check the blower motor mount screws for tightness
Check pneumatic inflatable gasket
Check the all silicon gasket seals
Coating Machine:
Maintenance Interval: Monthly
Maintenance Task
Check the pneumatic system
Check and clean the pre filter
Check the spray gun & air connection
Check the pan motor, gear box drive belt
Check the pan bearing & gear box bearing
Check the door seal, pan bearing, hinges, and tightness
Check the blower motor, blower housing & heat exchanger
Check the solution mixing pneumatic motor and grease the bearings
Check the flow switch, water solenoid valve, bar limit switch & hose retighten
Maintenance Interval: 6 Monthly
Maintenance Task
Check the spray pump
Check the Electrical Wire Connection
Check the main gear box & gear oil level
Grease the bearing and if it is damaged then replace the same
Yearly
Check the gear oil level and add oil if it is necessary
Check the door seals, pan bearing, coupler hinges and joints
Check the blower motor and heat exchanger unit motor hose
Blister Machine:
Maintenance Interval: Monthly
Maintenance Task
Check the Heater
Check the Cam Bearing
Check the Gear Oil Level
Check the Electrical Connection
Check the Pneumatic Connection
Maintenance Interval: 6 Monthly
Maintenance Task
Check the Blade
Check the Spring Tension
Check the electrical connections
Check the Roller Bearing & Bearing Pin
Maintenance Interval: Yearly
Maintenance Task
Check the Air filter
Check the Lubricated spring set
Check the Gear oil and change if it is necessary
Check the Oil spring set, if damage than change the same
Autoclave:
Maintenance Interval: 03 Monthly
Maintenance Task
Check the door seal.
Check the gasket of all TC clamp connections.
Check for any lime build up in the vacuum pump discharge pipe.
Maintenance Interval: 06 Monthly
Maintenance Task
Check the strainers fitted with the machines
Check the pneumatic valve & solenoid valve seal and gasket
Check the operational status of the non return valve fitted on sterilizer
Maintenance Interval: Yearly
Maintenance Task
Check the all electrical connections
Check the emergency button is working properly
Visually check the condition of the mechanical chain
Check the pneumatic cylinder opening/closing the door
Visual check for any water leakage from the vacuum pump body
Encapsulation Machine:
Maintenance Interval: Monthly
Maintenance Task
Check the Gear Oil Level
Check the Vacuum Oil Level
Check the Bearing Condition
Check the Electrical components
Check the Main Motor Connections
Check the Powder Sensor Sensitivity
Maintenance Interval: Half Yearly
Maintenance Task
Refill Vacuum Oil if necessary
Check Gear Oil and change if necessary
Bottle Washing Machine:
Maintenance Interval: Monthly
Maintenance Task
Check the filters
Check the gear box
Check the float switch
Check the pneumatic line
Clean the electrical panel board
Check the nozzle and clean it if necessary
Maintenance Interval: 3 Monthly
Maintenance Task
Check the Gear oil level
Check the bearing condition
Check the main motor connection
Check the electrical all components
Maintenance Interval: 6 Monthly
Maintenance Task
Check the Gear oil and change the same if required.
Conveyer Belt:
Maintenance Interval: Weekly
Maintenance Task
Check the main motor
Check the roller bearing
Check the gear box with oil
Check the roller adjustment belt
Check the chain, clean and grease
Maintenance Interval: Monthly
Maintenance Task
Check the Gear oil level.
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
Check the main motor
Check the roller bearing
Check the gear box with oil
Check the roller adjustment belt
Check chain and clean and grease
Maintenance Interval: Monthly
Maintenance Task
Clean the Electrical panel board.
Check the gear oil and change, if it is needed.
Blending Machine:
Maintenance Interval: Monthly
Maintenance Task
Check all safety interlock and mechanisms.
Check the machine for irregular noise or vibration.
Check compressed air filter and clean/change if required.
Check Pneumatic System (Air Condition Filter and Regulator)
Maintenance Interval: Yearly
Maintenance Task
Check the double cone tool
Clean the electrical cabinet sensibly
Check the Gear Oil Level If need then replace
Check for any unfamiliar noise or shaking from the machine
Two Head Liquid Filling Machine:
Maintenance Interval: Monthly
Maintenance Task
Check the roller bearing
Check the gear box with oil
Check the piston and the disks
Check the main motor with v-belts
Check and grease all movable parts
Maintenance Interval: 6 Monthly
Maintenance Task
Check the overall cleaning
Check the electrical all component
Check the pistons and disks for any damage
Manufacturing Vessel:
Maintenance Interval: Monthly
Maintenance Task
Check gear box with oil
Check main motor with V-belt
Check roller bearing of the pump
Check and grease all movable parts
Check the transfer pump of the vessel
Maintenance Interval: half Yearly
Maintenance Task
Check the overall cleaning
Check the electrical all component
Check the mechanical seal of the pump
Tablet Compression Machine:
Maintenance Interval: Monthly
Maintenance Task
Check the V-belt
Check the main shaft
Check the warm gear
Check the pressure roller
Check the electrical cabinet
Check the pressure adjust knob
Maintenance Interval: 6 Monthly
Maintenance Task
Check the filling depth
Check the Gear oil level
Check the hydraulic oil level
Check the electrical connection
Check the powder level sensor
Maintenance Interval: Yearly
Maintenance Task
Check the Gear oil viscosity
Check the electrical component
Check the Hydraulic oil if need replace it
Cap Sealing Machine:
Maintenance Interval: 6 Montly
Maintenance Task
Check the gear oil level
Check the cap sealing holder
Check the motor piston with grease
Check the pressure adjustment knob
Check the bearing with gear premium
Maintenance Interval: Yearly
Maintenance Task
Check the pneumatic motor
Check the electrical cabinet
Check the pressure adjustment knob
Check the motor with bearing piston grease
Check the gear oil level if need change the same
Stability Chamber:
Maintenance Interval: Monthly
Maintenance Task
Clean the PT100 Sensor
Check the door pipe connection
Check the chamber door closing
Check the operations of safety thermostat
Check the condenser fan, if found loose then tighten it
Check the proper earthling connection to the stability chamber
Maintenance Interval: Half Yearly
Maintenance Task
Check the evaporation tray
Clean the condenser by blower air through
Check the water immersion heater and reservoir tank
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
Check the pneumatic component
Check the electrical wire connection
Check any unusable noise or vibration
Check all safety interlock and mechanism
Maintenance Interval: 6 Monthly
Maintenance Task
Check the electrical wire connection
Check the oil level and viscosity of oil manually
Rapid Mixer Granulator of Product department:
Maintenance Interval: Monthly
Maintenance Task
Check the main motor with gear
Check the chopper motor bearing
Check the impeller and motor bearing condition
Maintenance Interval: 6 Monthly
Maintenance Task
Check the Electrical Wire Connection
Check the V-Belt & Motor Condition
Check the Mechanical Seal or Bearing
Check the Main Gear Box Gear Oil Level
Maintenance Interval: Yearly
Maintenance Task
Check the discharge valve’s motor condition.
Check the gear oil level if it is needed then replace the same.
Sampling Booth:
Maintenance Interval: fortnightly
Maintenance Task
Clean the pre filter (G4).
Check the motor condition.
Check the machine’s all nuts and bolts.
Maintenance Interval: Monthly
Maintenance Task
Clean blower motor.
Check electrical constituents & motor.
Check for any unfamiliar noise or vibration.
Dispensing Booth:
Maintenance Interval: Forthightly
Maintenance Task
Clean pre filter (G4).
Check the motor condition.
Check the machine’s all nuts and bolts.
Maintenance Interval: Monthly
Maintenance Task
Clean the blower motor.
Check electrical components and motor.
Check for any unfamiliar noise or vibration.
Solution Mixing Tank:
Maintenance Interval: 6 Monthly
Maintenance Task
Check the baffle plate
Check the pneumatic motor
Check the pressure adjustment knob
Check the pneumatic motor piston grease
Maintenance Interval: Yearly
Maintenance Task
Check the baffle plate
Check the pneumatic motor
Check the Pressure Adjustment knob
Check the pneumatic motor piston grease
Vacuum Pump
Maintenance Interval: Fortnightly
Maintenance Task
Clean the filter
Clean the O ring
Check the nut bolt
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
Maintenance Task
Check housing flange
Check the motor body
Check the motor flange
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
Check airline
Check gear box
Check all grease point
Check all pulley and Belt
Check vibration and abnormal noise
Check all screws on driving units, tighten it if necessary
Maintenance Interval: Yearly
Maintenance Task
Check the earthing
Check the switches
Check voltage and frequency
Sticker Labeling Machine:
Maintenance Interval: Monthly
Maintenance Task
Check the pneumatic system
Lubricate the motor bearing as needed
Check all screws on driving units & tighten it if required
Maintenance Interval: Yearly
Maintenance Task
Check the earthing
Check the inverter connection
Check the voltage & frequency
Check the electrical control unit
Automatic Dehumidifier:
Maintenance Interval: Monthly
Maintenance Task
Check the fan.
Check for somewhat leakage
Check the cooling coil
Check the gas pressure of the compressor
Remove the condenser water from container
Check the screw on driving units & tighten it if needed
Maintenance Interval: Yearly
Maintenance Task
Check the electrical switches
Check the electrical connections
Tablet De-duster:
Maintenance Interval: Monthly
Maintenance Task
Check the main motor
Check the gear oil level
Check the roller bearing
Check the gear box with oil
Check the roller adjustment belt
Check the electrical all component
Check the chains and clean & grease
Maintenance Interval: Yearly
Maintenance Task
Check the electrical panel board & overall cleaning
Check the viscosity of gear oil & change it if necessary
Inkjet Printer:
Maintenance Task
Maintenance Interval: Monthly
Check the vacuum pump
Check the ink spray needle
Check the electrical cabinet
Check the solvent or ink status
Check the pressure adjust knob
Check the main ink head of printer
Inkjet Printer:
Maintenance Task
Maintenance Interval: Monthly
Check the main head
Check the vacuum filter
Check the ink expire date
Check the electrical connection
Check the ink or solvent level sensor
Vial Washing Machine:
Maintenance Interval: Monthly
Maintenance Task
Check the Nozzle
Check the Gear Box
Check the Float Switch
Check the Pneumatic Line
Check the Electrical Panel Board
Check the Pneumatic Line, Connector & Filter
Maintenance Interval: 3 Monthly
Maintenance Task
Check the Gear Oil Level
Check the Hot Water Line
Check the Bearing Condition
Check the Main Motor Connection
Check the Electrical All Component
Check the Powder Sensor Sensitivity
Check the Turret and Moving Parts Clean and Grease
Maintenance Interval: 3 Monthly
Maintenance Task
Change the Gear Oil
Refill the Vacuum Oil
Clean the Overall Machine
Multi Mill:
Maintenance Interval: Monthly
Maintenance Task
Check the pulley
Check the hopper will blades
Check screws on driving units, tighten it if required
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.
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.
6.2Quality 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”
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-
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].
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-
Career Development Programme
Company business strategy
Company Policy
Control of Entry with illness and open lesion
Cleaning and sanitization records
Departmental Organogram
Dust control and Management Record
Employee list of Organization
Employee Retention Programme
Environment Health and Safety Programme
Entry/Exit Register Management
Final Settlement Procedure
Firefighting System
Fire drill Programme
Human Resources Programme
Handling of laundry procedure
Handling of sewage during production factory
Handling of Accidental hazard and record keeping
Handling of ETP sludge
Identification of Fire Assembly Point
Induction Training Record
In-plant training Management
Job description of Employee
Leave Management Process
Leave Management Process
List of First Aid Item
List of Departmental SOP
Manpower Development Plan
Medical Checkup process for new comer
Previous Audit Report and Incomplete Action Plan List
Pest and Rodent control procedure
Recruitment Process
Short leave/Emergency Leave Register
Training Need Assessment
Yearly Training Calendar
Waste Management Procedure
SOP on
Canteen Facility Management
Charge Hand Over and Take Over of Security Department
Cleaning Procedure for Insects Killer
Company Policy for Visitors
Dress Coding System and Gowning Procedure for Working Personnel and Visitors
Employee Motivation
Entry & exit procedure
Factory gowning management
Factory Gowning Cleaning and Management Procedure
First Aid Kit Management Procedure
House-Keeping and Cleanliness
Induction of the New Employee
Laundry Procedure for Working Dresses
Medical Examination of the Working Personnel
Measures for the Working Personnel at the Plant
Management of Personal Protective Equipment (PPE)
Occupational Health and Safety
Organizational Behavior
Process of Pest and Rodent Control at the Plant Premises
Sanitizing Procedure for Sink and Floor Drain Sanitization
Security Awareness
Selection and Recruitment of Manpower
Training of Employee
This all about the Audit Checklist for HR Department but not limited to.
