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Sterility Test, how to perform Sterility Test in the best way?

Sterility Test

Sterility test is the basic requirements for the products claim it is sterile for its intended use. This is the core requirements to ensure the sterile status of the products which never contain the viable microorganism at the time of use to the patients or must confirm before released for sales.

Sterility testing need to be as precise as possible due to its critical point of use such as pharmaceutical products, tissue materials, blood products, serum preparations, vaccine preparation, Insulin preparations, powder for injections etc. and the other products which are claim to be sterile or free from viable microorganisms.

Various types of firm, food factory, pharmaceutical industry, beverage manufacturers, and medical device manufacturer’s etc. company use Sterility testing procedures which company deal with the sterile products and this is mandatory for them. Generally, a microbiologist or a group of microbiologists are involve to perform the sterility test based on company work flow.

A Consistent sterility testing is the core to the develop or validate a specific product or procedure. Continuous robust test method is mandatory get the accurate test result repeatedly. A robust quality infrastructure is required to support the biopharmaceutical, pharmaceutical, and medical device industries.

Direct Inoculation and Membrane Filtration Methods

Sterility testing is required to ensure viable contaminating microorganisms are not evident in a product. This testing is conducted by direct inoculation or membrane filtration methods and can be performed in an isolator or cleanroom environment.

Sterility Testing Techniques

There are several sterility Testing are available-

Recommended Sterility Test: Two Types

Direct inoculation
Membrane filtration

Additional Test: Two Types

Bacteriostasis/fungistasis testing–b/f testing
Vaporized Hydrogen Peroxide (VHP) ingress testing

Direct Inoculation

Here two types of media are used to directly inoculate the test article for the determination of the both aerobic and anaerobic microorganisms. The both media are for 14 day from the start of the test day and sporadic observations as well as final/end day observations are done to check the any type of evidence of microbial contamination.

A suitable volume of growth media is used to inoculate small volume of sample which is directly collect from sample container by applying aseptic technique then it incubate for 14 days. Direct Inoculation Sterility Testing has some significant limitations. The sensitivity is low for the test as small volume of a full container is inoculate to the respective culture media. At the starting of inoculation, if the sample appears cloudy or turbid then this very challenging to detect the turbidity and the end of the test period for the microbial growth.

Membrane Filtration Sterility Testing

Here the simultaneous filtration of test sample and standard preparation perform through two membrane filters and the samples are subsequently incubated for 14 days from the start of the test day, and finally check/determine the visibility of the microorganisms both aerobic and anaerobic.

The filterable pharmaceuticals product are subject to Membrane Filtration Sterility Testing which have been described in EU Pharmacopoeia < 2.6.1>, USP <71> & JP Pharmacopoeia <4.06>. To perform the test 0.45 µm membrane filter is used to pass the sample, then culture medium is added for incubation. The sensitivity of the test is more precise as the whole or composite sample is passed through the filter. Another best opportunity of the Membrane Filtration Sterility Testing is, its rinse away components present in the sample which may cause the turbidity or inhibit growth as for example preservatives or antibiotics.

Bacteriostasis/Fungistasis Testing–B/F Testing

Bacteriostasis/fungistasis testing is perform in conjunction with the sterility test evaluate whether or not the test article is inhibitory to the growth of the different microorganisms. To evaluate the sterility result Bacteriostasis/fungistasis test is essential to ensure that test article don’t contain any antimicrobial properties and it don’t inhibit the detection of microorganism at sterility test.

Vaporized Hydrogen Peroxide (VHP) Ingress Testing

An isolator required to perform the Vaporized Hydrogen Peroxide (VHP) Ingress Testing which undergo undergoes VHP decontamination. This assay assesses if VHP enter to the test article is apparent that may affect the validity of the result.

What is Sterility Test USP <71>?

Sterility test USP <71> is the chapter of USP[United States Pharmacopeia] which represents how the sterility test to be perform, and the detail description, methodology and how the product to be tested based on the fill volume and sample size.

Media use in sterility testing

The sterility testing of the all product subject to sterile require two types of media which to be cultured in separate two media. In sterility testing, two types of culture media are used to promote the growth of residual anaerobes, as well as aerobes and fungi.

FTM[Fluid Thioglycolate Medium] and SCDM[Soybean Casein Digest Medium], these two type of media are used use to culture anaerobic and some aerobic bacteria and fungi.

Generally FTM is use for culture of anaerobic and some aerobic bacteria on the other hand, SCDM is use for fungi and aerobic bacteria. Before examination the samples are incubated for 14 days at 32.5°C and 22.5°C. Media must be turbidity free. Presence of turbidity in the respective culture media subject to growth of microorganism and it must be investigate.

Sterility testing methods for medical devices

For medical devices testing, direct transfer sterility testing is recommended. The respective devices are tested is in direct contact with the designated test media during the incubation period where microorganism is growing on or in the device to be check. Transfusion and infusion assemblies related products which contain fluid pathway declared sterile then product flush sterility testing is preferred for this type of product. Here a rinsing fluid is used to flush the product lumen then the elute is passed through the membrane filter and after that it place on the suitable media for incubation for 14 days.

Sterility Testing Procedure

Precautions:

Be assured of strict devotion with aseptic technique and no occurrence of secondary contamination in every step of the test. Traffic in the LF workbench should be reduce and well-ordered. Use cellulose acetate membrane filters when strongly alcoholic solutions are subject to filter. If the solution being tested has antimicrobial properties, rinse the membrane at least three times with sterile dilution fluid.

Avoid piercing/ splitting of HEPA filter with liquid and spraying of solutions on the workbench. Use single syringe for single batch or test and avoid touch contamination of the needle and plunger of the syringes. All rubber stoppers of vials and neck of ampoules should be out of hand touch as hands are clean but not sterile. Check all the media for clarity as well as sterility before use. Perform positive control/growth promotion test in another separate area from sterility test area under Bio-safety Cabinet.

Media and Diluents:

Tryptone Soya Broth (TSB)

Fluid Thioglycollate Medium (FTM). [When medium is stored, store at a temperature between 2ºC and 25 ºC in a sterile, air tight container. If more than upper one third of the medium has acquired a pink color, then to remove the pink color, the medium may be restored once by heating the containers in a water bath until the pink color vanishes and by cooling quickly.] USP Diluting Fluid A/rinse solution (1g/L peptone water/Sterile water for injection)

USP Diluting Fluid D (To each Liter of Fluid A/rinse solution add 1 mL of polysorbate 80, adjust to a pH of 7.1± 0.2). For Cephalosporin/Penicillin, add a quantity of sterile β lactamase, adequate to deactivate any residual antibiotic activity on the membranes after the solution of the test specimen has been filtered. Filtered 70% IPA (Isopropyl Alcohol).

Prepare these dehydrated mediums and ensure effectiveness of the media before, or in parallel, with the sterility test on the product subject to be examined. Growth promotion test of medium should be justified.

Method of Testing:

Membrane filtration
Direct inoculation

Criteria of membrane filter:

Filter I: Cellulose Nitrate Filter[CNF] for aqueous, oily and weakly alcoholic solutions and Filter II: Cellulose Acetate Filter[CAF] for strongly alcoholic solutions.
Diameter of membrane filter: 47 mm
Pore size of the membrane filter: Not greater than 0.45 µm.

Test sample:

Sterility test is a destructive test [You can’t return the test sample] and it is impossible to test every single item for sterility. Sample for testing should be representative of the batch, which ensures that the results of the tests are substantial. Arbitrary samples are optimally selected every Lth unit, where L = the total units in the batch per number of sample required.

The following number of samples should be used in sterility test described in Table – 1 and Table -2.When the test samples are turbid and is impossible to filter the samples follow the direct transfer method unless in other case follow membrane filtration method.

Sample preparation:

Excessive care must be exercised when opening an article so that the sample to be tested for sterility is not contaminated by Microorganisms present on the exterior part of the container. The exterior surfaces of ampoules and closures of vials must be cleansed with 70% IPA or Hydrogen peroxide. Allow for 10/15 minutes and assemble the sampling unit’s previously sterile tray at inverted position.

Transfer the samples through pass box into the sterility testing area. FTM [Fluid Thioglycollate Medium] and SCDM[Soybean-Casein Digest Medium] or TSB[Tryptone Soya Broth] is used for the sterility test. Prepare these dehydrated mediums.

Before use, each batch of medium should justify for sterility by incubating portions of the medium for not less than 7 days. Growth promotion test [Nutritive properties] should be justified.

Test for Sterility of the product/material [Membrane filtration method]:

Prepare required amount of FTM, TSB, and USP Diluting Fluid–A and sterilized it. After completion of sterilization transfer all testing materials and accessories into sterility testing area by opening sterile side door of the autoclave.

Enter into the sterility testing area through change room. Clean & sanitize the working place. Accumulate the Sterilized filtration unit cautiously, using not more than 0.45µm cellulose nitrate filters (47mm dia.). Convey samples and other equipment into testing area from pass box after cleaning the surface with 70% IPA.

For Raw Materials transfer aseptically 5 -10 gm of tested sample into 500 ml screw caped conical flask containing 200 ml of USP diluting fluid-A and shake gently when it completely dissolve. For Finished Product collect required amount of test sample (see step Table) & transfer aseptically 300 mg of solids into a 500 ml screw caped conical flask containing 200 ml of USP Diluting Fluid-A and mix or constitute, as directed in the labeling, the containers and transfer a quantity of liquid equivalent to about 300 mg into a 500 ml screw caped conical flask containing 200 ml of USP diluting fluid-A.

Transfer the whole content to the filter cup assembly under strict aseptic condition. Filter the whole content with aid of vacuum pump [negative pressure] from the filter cup. If the tested sample under test has inherent Bacteriostatic & Fungistatic properties or contains preservative, rinse the filter paper using USP Diluting Fluid A.

After completing the previous step, cut the filter paper into two equal sections with sterile scissor and aseptically transfer into 100 ml bottle containing TSB & FTM media separately. Mark 1×100 mL of sterile FTM and 1×100 mL of sterile TSB medium without any sample and inoculum, as negative control.

After finishing of the test transfer out all the materials through pass box, clean the working place thoroughly and sanitize with approved disinfecting solution before leaving the area.

Direct Transfer Method:

Prepare required amount of FTM, TSB, (distribute it in screw cap 100 ml bottle) and USP diluting Fluid-A and sterilized it. After completion of sterilization transfer all testing materials and accessories into sterility testing by opening sterile side door of the autoclave.

Enter into the sterility testing area through change room. Clean & sanitize the working place. Prepare required amount of test sample (as per mention Table) and aseptically transfer it into 500 ml screw caped conical flask containing 200 ml of USP Diluting Fluid-A, and shake it gently.

Agitate the flask and aseptically withdraw 5 ml of test specimen into both of sterile TSB & FTM medium. Mix each test specimen with the appropriate medium, but do not aerate excessively. Incubate the test mixture and both negative controls as directed in the Incubation condition. Examine the media visually for growth.

Where the material being tested renders the medium turbid, so that the presence or absence of microbial growth cannot be determined by visual examination, transfer suitable portions of the medium to fresh containers of the same medium at least once during the period from the third to the seventh day after the test is started.

Continue incubation of the original and of the transfer containers for a total of not less than 14 days from the original inoculation.

Sterility Test of Syringes ( 5 mL, 10 mL & 20 mL)

Take the required quantity of the material followed by previously mentioned table. Aseptically disassemble the syringes into the components like barrel, plungers, needle and needle shield.

Transfer half of the syringe components into one media bottle having sufficient quantity of the FTM and another media bottle having TSB so that components can submerge completely within media and if require pour additional media.

Select the bottle for sterility test on the basis of the size of the components of syringes so that upon addition of media sufficient air space will be available.

Incubation Conditions:

All the test containers, incubated for not less than 14 days at 32.5 ± 2.5⁰C for the Fluid Thioglycollate Medium and at 22.5 ± 2.5⁰C for the Soybean-Casein Digest Medium or Tryptone Soya Broth Medium regardless of the method used for sterility testing.

Observe the media bottle on a periodic basis over Digest Medium regardless of the method used for sterility testing. Observe the tested as well as negative control incubated media bottles on each working day for any kind of macroscopic evidence of microbial growth and record the results in the report sheet with sign and date of the observer.

Interpretations of the Results:

At intervals during the incubation period and the completion of the prescribed incubation time, examine the media for any visible growth (Turbidity). If confusion arises, make subculture on TSA medium and/or justify evidence of growth.

If no evidence of growth is found, the preparation being examined, pass the sterility test and issue report form (Annexure I). If evidence of growth is found, isolate and identify the organism and make a full case investigation.

If the cause of microbial growth failed to reveal, perform repeat test with same number of test sample. Take double number the sample in case of high risk product.

Download : Appendix-I-Sterility Test Report

Download : Appendix-II-Sterility Test observation Register

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Validation Master Plan, How to write for a GMP compliance firm

Quality Assurance, Validation

Validation Master Plan[VMP] encompass all type of validation activates of a site especially for the new firm, the firm must be validated before run any routine commercial production. The validation activities which consider the major area as Facility, Utility, Machine, Process etc.. Facility, utility, and machine must be validated before run the production operation.

Validation procedure and Validation Master plan is not the same and doesn’t implies the same thing. Validation protocol describe the specific procedure to perform the specific activities where as Validation Master Plan is the series of plan/schedule which describe the plan with a tentative define timeline. Any plan/schedule may be change which to be cover by raising deviation management with proper justification and action to be triggered followed by CAPA.

Validation Master Plan is beneficial for planning purpose and subsequently identifying the related resources to complete the assigned activates on due time. It covers the all type of major documentation like procedures, processes, product, facilities, utilities and equipment.

How a Validation Master Plan works?

Validation master plan is the core guidance of the firm which implies that how the validation activates of the firm will perform within a time frame. It details the activities of the all functional department like production, quality control, Engineering will operate their activities regarding validation events.

The plan demonstrate by the Validation master plan is set upon the agreement of the all functional department and any type of failure is properly justified which satisfy the regulatory body. The proper implementation of the VMP of the respective firm denote that they have the proper control over their quality system.

Functions of the Validation Master Plan

Management learning

Top management of the company is not concern about the requirement of the qualification and validation activities of the respective firm. Here VMP plays the major role and provide the essential information to the company top management. The content of the VMP describe the total quality requirement events of the validation process. It also denote that only the properly validated facility can provide the repeated/continuous quality product through daily activities.

Project nursing and management

By preparing the Gantt chart from the content of the VMP, the management can track the activities of the new facility and set a tentative deadline for the competition of the defined activities. Everyone will be proactive when set a tentative deadline with proper justification through a site quality review meeting. Assigned personnel must be monitored for the progression of the events by daily /weekly /fortnightly/ monthly then VMP will be fully effective and action will cover on due date.

Conducting the validation program

Validation master plan describe the all events in the validation process and the qualification of the processing equipment’s and utilities. As the VMP provide the timeline for the completion of the defined activates base on the criticality. All related resource must be on site to conduct the validation activities and recheck/double/ triple check may be conduct before starting validation activities, for any shortcoming notify the same and after solving the events proceed to validation activities.

Planning purposes

As the VMP detect the list of resources which is required to perform the validation activities in a time line then the list of document may affect by this activity-

Equipment
Facilities
Product
Processes
Procedures
Utilities

Criteria of a Validation Master Plan

VMP require specific preparedness and vigorous planning of different steps in the particular process. All type of activates need to perform in due time as per approved working plan avoiding any type of major/critical deviations. Beside this a VMP is generally written off as-

Multidisciplinary methodology:

This is not the one man job, its require multidepartment involvement, various type of SME [Subject Matter Expert] from various department are involve to perform the specific job. Expert such as chemical analysts, pharmacists, microbiologists, technologists, engineers, metrologists, and SME from QA departments must involve to this activities.

Time bound:

Any type of validation

Generally validation work is submitted to rigorous time schedules. These studies are always the last stage prior to taking new processes, facilities into routine operation.

Costing matters:

To run a successful validation activities to the site, huge resources and expert personnel are involve so that no deviation occur on the site. Lot of financial involvement require to perform the designated activities. A new machine/equipment may be involve to solve the emergency issue.

List of critical point of Standard VMP

All VMPs must include the following:

Title page with Authorization where appropriate signing with date will be present. Title page must be include title of the document, document number and version no. and Signature from the appropriate body including Head of site quality. List content to be present on a VMP-

Table of contents
Abbreviations and glossary
Validation plan
Purpose and approach to validation
Scope of validation
Roles and responsibilities
Outsourced services
Deviation management in validation
Change control in validation
Risk management principles in validation
Training
Validation matrix
References

The table content is the brief of the major substance/content present in the VMP. It contains all of the critical area of VMP. Page no. to be mentioned on the table of the content page along with the major content. It will denote where will find the major content of the VMP.

Abbreviations and glossary

Abbreviations and glossary provides necessary information’s to the reader regarding the various term or short/abbreviate form use in the VPM which may not familiar to the respective reader.

Validation plan

A VMP implies that what should be validated and when, where, how and why it should be executed. Critical process mention on the VMP must breakdown into several parts and criticality must identified to perform require validation.

Purpose and approach to validation

Purpose provides an overview of the every process also describe validation approach with supporting data. It must be sum up clearly so that the respective user can understand the actual process/procedure by tracking the document. Validation approach states the persistence of the VMP denoting critical process, equipment and system as described.

This methodology confirm that all validation events to be conducted in prospective manner following approved protocols. VMP speaks about the change control and qualification of equipment and systems and confirm the stipulated events has been done based on existing policies and procedures.

Scope of validation

Scope of the VMP describe all evets relating to the processes, systems, equipment, utilities, and procedures which may affect the quality of the product at the manufacturing site.

Specific equipment, utilities, systems, and procedure be mentioned properly and validation execution to be done based on the documented risk assessment. Define clearly which area will be under validation and where not under the scope. Procedure to be describe in such a way so that anyone possess the same understanding to coverage VMP.

Roles and responsibilities

This area specially denote the dedicated responsibility for the designated department. Generally validation department/team is responsible for preparing all type of validation protocols, validation reports, List of SOP’s deviation reporting, and change control procedure and achieving, storage of validation related all documents.

Generally, Engineering, Production, QC, Microbiology and QA personnel prepare the validation documents as when required based on define timeframe subsequently. Quality Assurance department is responsible to review the all protocol, reports, SOP’s etc. then approve the same.

Outsourced services

Any type of out sources activities regarding qualification and validation must be mention the validation master plan and record/supporting documents/agreements must be keep the same. Certified vendor to be involve to the validation activities, before engage the validation/qualification activities vendor competency certificate to be check.

Deviation management in validation

Any deviation regarding validation to be address and record must be keep for further clarification, if machine involve then call the supplier to resolve the problem. All of critical deviation must be investigate and corrective action to be taken. All validation report to be approve before starting the operation.

Change control in validation

VMP must implies all change management which have the potential impact on the validated process/system must be notify and it should be handle with the existing change management procedure.

Risk management principles in validation

Quality Risk Management Procedure to be define on the Validation Master Plan as to perform the validation activities, quality risk may be the major to be notify same and record must be done and impact to be analyze properly through FMEA[Failure mode and effects analysis] method.

Training

The defined personnel who will perform the validation activates must be trained properly and to be ensure that they have the proper knowledge and skill to perform the right job at the right time.

All validations

This include the following area-

Analytical method
Cleaning
Computer validation
Equipment
Premises
Processes
Qualification
Revalidation
Utilities

The description of the major area must be include VMP such as Manufacturing, Material Management, Facilities, and Central Plant. Attachment with VMP must define the GMP compliance area and non-GMP compliance areas. Describe the cleaning validation strategy and manufacturing process steps, use process flow diagram to describe the specific product manufacturing activities with major equipment involvement on the diagram. Performance qualification of the major equipment to be done showing that it repeats its intended use subsequently.

Validation matrix

Performing an effective validation matrix by prioritizing the critical validation at first then the next one. In this way the VMP activities may be more fruitful. List the all critical validation then perform the task as per justified time frame.

References

List of references to be add at the end of the VMP documentation. Proper guideline reference is mandatory to prove your documented evidence.

Writing the VMP

To write the effective VMP, a team may be form due to a single/individual/specific person didn’t contain the all idea/knowledge regarding different activates. A QA person may not be expert about Engineering activates and a QC person may not be expert about production activities, so a team from different functional department may be effective way to gather comprehensive knowledge from different perspectives then write down the right VMP.

Involving the multidepartment people from different parts confirm that all equipment, utilities, processes, and systems has been properly addressed on the VMP. T write an effective VMP, every team member must be proactive to address the every point of view seems critical to his side.

What “WHO” says about Preparation of VMP?

“A manufacturer should have a validation master plan that reflects the key elements of validation. It should be concise and clear and at least contain reference to/have a short description”.

List of Major content of VMP as per WHO GMP guideline-

Analytical method validation
Change control
Cleaning validation
Computerized system validation
Deviation management
Equipment & instrument qualification
Outsourced services
Personnel qualification
Premises qualification
Process validation
Validation matrix
Validation policy
References
Risk management principles
Roles and responsibilities
Scope of qualification & validation
Training

Conclusion

A well described VMP is the true asset of the firm as well as the critical document to avoid the regulatory noncompliance. An incomplete VMP always brought more 483 with subsequent warning letters from FDA. A standard VMP must be more precise, to the point and actual to the system, process, and procedure.

Every sentence of the VMP must be “may”, “may be”, “should be” etc. free, sentence must be in active form in present tense. A well decorated VMP implies the organization positive image as well as quality products avoiding non-compliance, deviation etc.

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HEPA filter and its multipurpose use in different area

Engineering, Facility

HEPA filter, High-Efficiency Particulate Air/ High-Efficiency Particulate Arrestance Filter / High-Efficiency Particulate Absorbing Filter is known as HEPA filter denote higher degree of efficiency. The efficiency level denote the grade of the HEPA filters. There are several grades of HEPA filters available as per their area of application.

A standard HEPA filter must remove the particles from the air at least 99.5%[EU standard] or 99.97%[ASME,US.DOE] having particle diameter equal to 0.3 μm and subsequently increase efficiency with particle diameter greater than or equal to0.3 μm.

All type of standards HEPA filter generally retain particle and microorganism like dust, pollen, dirt, moisture, virus (0.02-0.3 μm), bacteria (0.2-2.0 μm), Bacillus subtilis, submicron liquid aerosol (0.02-0.5 μm), Penicillium citrinum, Aspergillus niger, Clostridia, Staphylococcus epidermidis, Bacilli, Bacteroidia, photocatalytic oxidation (PCO) etc.

HEPA filters use in wide area since its commercialization at 1950 where need to control contamination-

Aerospace industry
Cosmetic industry
Materials dispensing area
Electronics
Food Industry
Hard disk drives mfg. industry
Hospitals
Medical devices
Microbiological Lab
Nuclear Plant
Pharmaceuticals
Sterile products mfg. facility
Semiconductor industry
Vaccine and blood products mfg. area
Vehicle industry

Type of HEPA filters

Generally HEPA filters can be classified as [A], [B], [C], [D], [E] and [F]. Types testes are demonstrates on the following table.

HEPA filter, classification of HEPA filter,

How it works?

All type of HEPA filters are generally composed of mat where fibers are randomly arrange, these fibers are actually set of poly propylene or fiberglass varies diameter between 0.5 and 2.0 micrometers. Frequently use tangled bundles of fine fibers to prepare these filters. Air passes through the convoluted pathway crated by the tangled bundles of fine fibers.

Actually this fibers act like sieve which retain the big particles which subject to try pass through it. Most time the smaller particles can’t hold its motion when they are passed with air, in result the small particle crush with the fibers. As per Brownian motion, the small particle possess the little materiality to move randomly with air as these particles are suffered to bombard action.

As the small particles crush with the fibers, here the key factors are mainly filter thickness, fiber diameter and velocity of the air. The air space between the HEPA filter subject to greater than or equal to 0.3 μm provide high level of efficiency. In sieves or membrane filters, particles which are less than the pore or openings can pass through but in HEPA filters the particles are attached to the fibers. There are several mechanisms has been identified which play the major role trap the particle to the pore.

Diffusion

All the particles under 0.3 μm retained by the HEPA filter in diffusion method. This the main theme of the Brownian motion where smaller particle below or equal to 0.1 μm in diameter are hindered and trapped in the filter. This mechanism is not prominent is low velocity of air.

Interception

Particles which are subject to flow in a line come with same radius/diameter of a fiber and adhere to it, this is very prominent to mid-size particle and which are retain by this process.

Impaction

Particles with higher diameter subject to unable to pass the fibers and directly retain on them, the effect increase subsequently with the air velocity.

Particle having size at or below 0.1 μm diameter, diffusion method is predominant and particle above0.4 μm predominant to impaction and interception. The MPPS [Most Penetrating Particle Size] is 0.21 μm, here the impaction and interception are remarkably inadequate. And this this point consider the weakest point of HEPA filter. The classification of the HEPA filters remarkably depend on the particle retention capacity at or below or equal to 0.3 μm particle size.

What is Gas filtration?

All types of HEPA filters are designed to retain particles but HEPA filters are unable to retain odor and gases molecules. HEPA filters can’t filter the odor or gases molecules. Alternative have been developed by British Armed Forces[BAF]. To filter the chemical vapors, organic compounds, volatile compounds, pet, cigarette, or flatulence odors, activated carbon filter or other filters are used.

HEGA [High Efficiency Gas Adsorption] filters plays the major role here, composed of Carbon cloth filters which is more efficient than granular activated carbon form. This filters [HEGA] designed by BAF to face chemical warfare.

Effective Usage of HEPA filter with Pre-filter

In a common air handing unit, a pre-filter[Carbon activated] use with the HEPA bag filter to extend the usage life/shelf life of more expensive HEPA filter. At the first stage of the filtering the pre-filter, removes the almost all type of dust, hair, particle from the air. Particles which can’t remove by pre-filters or escape from it then the fine particles remove by the HEPA filters in AHUs[air handling units].

Specifications of HEPA Filter

HEPA filters are defined by the US, DOE[United States Department of Energy] in almost all American industry which removes at least 99.97% of particulate at 0.3 μm in diameter. At the standard volumetric air flow, the minimal resistance of the air flow or pressure drop is around 0.044 psi[300 pascals].

In EU, filters are classified based on MPPS [Most Penetrating Particle Size] as HEPA, EPA, and ULPA where the average efficiency defined as “Overall” and the specific point efficiency defined as “Local”.

Marketing View Regarding HEPA Filter

Now a days some of the company highlighted the term “True HEPA” supposed to give assurance to the end user/customer to confirm that their filter is the original HEPA filter. This term “True HEPA” has no significant scientific value or no legal meaning. Some of the company marketed as designed as”99% HEPA”,”HEPA-style””HEPA-like,” “HEPA-type,” etc. which didn’t comply the HEPA standard[99.97% efficiency] and this type of material may not have the original test certificate of may not undergo any type test like filter integrity test.

Safety consideration of HEPA Filter

Mid-size particles ranges between 0.15 µm and 0.2 µm is considered hardest to filter through HEPA. The mechanism of working of HEPA filter is totally different from Ionic filters and Ozone filters which work through negative ions and ozone gas respectively. So HEPA plays a great role in pulmonary side-effects like asthma and allergies which are much lower with HEPA filters.

Where the HEPA filters subject to use in commercial grade, it is better practice to change the HEPA filter in every six month to hold its efficiency at desired level of work but if it use in residential purpose then it may be change in every two to three years. In the period of time, the efficiency of HEPA filters decrease day by day and failing to change the same in due to create hazard to the machine or system and particulate contamination spread day by day.

Applications of HEPA filters

Biomedical

HEPA filters generally remove the air borne particle, bacteria, virus and various type of organism resulting infections. High energy ultraviolet light units or panels with anti-microbial coating integrated HEPA filters are specially use to serve medical purpose to kill the live bacteria and virus which trapped by the filter media. Airborne disease transmission successfully protect by the special design HEPA filter which efficiency declared as 99.995%.

Heating, ventilation, and air conditioning[HVAC]

HVAC [Heating, ventilation, and air] technology uses HEPA filters to remove airborne particulate, dust, microorganism etc. in indoors and vehicle, greatly use in sensitive pharmaceutical product manufacturing where subject to clean room class. To ensure better environment and better health, HVAC play a major role various organization who are concern this activities.

COVID-19

HEPA filters plays a great role to get entrapped SARS‑CoV‑2 Airborne droplets which size approximately 0.125 µm even if they are present on the floor. Various type of HEPA incorporated mask are available at the current market which is the best solution to prevent the pandemic situation for personal use.

Motor vehicles

HEPA filters is using in the latest car, “Tesla Mode X” using HEPA filters since 2016 and now their update “Model S” also using the additional HEPA filter.

Vacuum cleaners

HEPA filters are also use in many well designed vacuum cleaners as a part of their filtration systems. This option of the vacuum cleaners plays beneficial role for the patients having asthma and allergy problem due to HEPA filters traps fine particles reduce to size 0.1 µm which is mainly responsible to induce asthma and allergy. Before using the Vacuum cleaner integrated with HEPA filters, check the filter efficiency [at least 99.97%] unless authorized. HEPA like, True HEPA, HEPA are not the actual term to declared standard HEPA efficiency.

A powerful motor is essential to provide adequate cleaning power due to the high density of the HEPA filters. A vacuum cleaners containing washable HEPA filters subject to more expensive. A standard high quality HEPA filter generally trapped the particles having 0.3 µm in diameter where a natural human hair is 50 to 150 microns in diameter. So a HEPA filter traps the particle which are reduce to several hundred times smaller than the standard width of Human hair.

Sometimes, is remarkably noticeable that some of the manufactured declared HEPA 4/HEPA 3/HEPA 2 etc. without proper explanation behind them. This is actually declares their MERV [Minimum Efficiency Reporting Value] rating. This the ability of the air cleaner filter to remove the particle, dust, and microorganism etc. which passes with air through the filter. The MERV scale distributed between 1 and 16 which declare the efficiency of the filters remove particle between 10 to 0.3 µm in size.

Vehicles

Airlines

All types of modern airlines uses HEPA filters to reduce contamination in the air. As most of the air in air plane cabin is recirculated, so this is crucial to filter the air using high grade of HEPA filters to avoid cross contamination.

Maximum quantities of standard pressurized aircraft brought air from the outside and circulate it the cabin exhausted it through the outflow valves in the rear side of the respective aircraft. Almost 60% of air comes from outside of the plane and 40% cabin air passes through the HEPA filters in well-designed aircraft.

What are drawback of HEPA filters?

Every filtration technology has the shortcomings that no filter can pass the 100% contamination free air. The efficiency is almost 99.9997% not 100% same for HEPA filters. Besides this the HEPA filter has the following two types of drawback which can dissatisfy to you to buy a HEPA filter/HEPA filter integrated equipment’s-

Insignificant Pollutants Can Escape Filter:

HEPA filters are effectively act on the particle size at equal to or above 0.3 µm, there various type of microorganism which particles are reduce <0.1µm can easily pass the HEPA filters. So using HEPA filters you can trap/remove all type of organism, this myth is actually invalid. The smaller particulate cause the serious health hazard for the patient/personnel who are previously suffering from asthma or allergic problem. Alternative technology should be used to face this tiny size particles.

Various type of Mold & Bacteria Growth on Filter:

When bacteria and mold gather on the air system on the HEPA filter, this accumulate organism have the potential chance to grow in geometric order. As the number of the microorganism tend to grow outside the filter then the health hazard outside the controlled environment growth day by day. To solve this issue, a UV light integrated HEPA filter to be use to kill the mold and bacteria at your indoor environment.

So what is the best alternative of HEPA filters?

The best alternative of HEPA filters are ULPA [Ultra-low Penetration Air] filters. HEPA filters remove particles size equal to or above 0.3 µm having efficiency of 99.97% where ULPA filters remove particles size equal to or above 0.12 µm having efficiency of 99.999%.

Can HEPA filters be Wash or Reuse?

All type of HEPA filters can’t wash. Some of the HEPA filter can be wash and some are not. If your HEPA filter labelled with “Washable” then you can wash the HEPA filter but a non-washable HEPA filter may be wash by appropriate way.

To rinse a HEPA filter decrease its efficiency and proper study didn’t found that how much efficiency loss upon rinsing the HEPA filters. Moreover, this has been proved that upon rinsing the HEPA filter, its efficiency loss due to losing/damaging of fiber occur in this time.

During cleaning of HEPA filter, if individual face lack of awareness, fall in serious health hazard upon accidentally taking some of pollutants from HEPA filter. After cleaning, drying activity must complete for a long time. Check the same before use as the wet filter is the great source of mold.

HEPA filters can be reuse if you can clean it properly. Use a vacuum cleaner to clean the filter rather than rinse it. Even non washable filter can be clean this way, proper measures to be taken before cleaning the HEPA filter. Avoid direct touching it. If you rinse your filter, the dry the filter properly by placing it outdoor. Before placing, shake the it to remove the water properly. Set it at outdoor in such way that it get air from all direction and faster the drying process.

After washing the filter may withheld its efficiency maximum 99.7% and you can was your filter every six months or once in a year but it is the best practice to replace the same. Some of the filter labelled with “Permanent” then you can’t wash it, just replace it.

Also Read

Poly Alpha Olefin(PAO) in HEPA filter Integrity Test at HVAC Qualification

HEPA filter and its multipurpose use in different area Read More »

Poly Alpha Olefin (PAO) in HEPA filter integrity test at HVAC qualification

Engineering, Premises and Equipment

Poly Alpha Olefin (PAO) is used in in HEPA filter integrity during validation of HVAC system in different pharmaceuticals. This is the best alternative of DOP which was previously used for the same purpose as PAO is subject to use. DOP was using long time for HEPA filter integrity test during HVAC qualification.

International Agency for Research on Cancer (IARC) has classified DEHP/DOP as carcinogenic 2B substance According to evidence from rodent studies which has also been identified carcinogen (cause cancer) for the human. For this reason scientist was trying to replace DOP for similar materials for a long time.

In 2021, JICA[Japan Air Cleaning Association] introduce a guideline to substitute the DOP[Dioctyl phthalate] with PAO[Poly Alpha Olefin]. PAO provides the same performance as provided by DOP additionally doesn’t provide any harmful/carcinogenic effect to human.

Food and Drug Administration[FDA] stated that the alternative aerosols are also suitable but it shouldn’t promote the microbial growth in the respective area. Generated aerosol ranges from PAO[Poly Alpha Olefin] is 0.1 to 1.0μm.

The aerosol generator, generate the PAO aerosol and subsequently passed through the HEPA[High-Efficiency Particulate Absorbing/High-Efficiency Particulate Arrestance/ High Efficiency Particulate Air having six types A, B, C, D, E & F] filter and then with the help of a Photometer the integrity is checked as 99.97% particle contains size 0.3 μm shouldn’t pass to the HEPA filter.

Chemically, PAO is the polymer of alpha-olefin which is the class of Olefins those contains double bond between first and second carbon of the polymer chains. Poly Alpha Olefin is the mixture of dimers, trimers and tetramers of 1-octane, 1-decane and 1-dodecane in chemically.

Poly alpha olefin is a polymer of alpha-olefin. Alpha-olefin is a class of olefins those have a double bond between first and second carbons of the polymer chains. PAO contains better lubrication properties and having greater viscosity compare to mineral oils. Poly-alpha-olefins have good lubrication properties and greater viscosity than mineral oils.

Poly alpha olefins are also used as a coolant in radiators and synthetic lubricants. Generally, the declared shelf life of PAO is 10 Years but when subject to open the container, the shelf life down to only one year. This is the best practice to protect PAO from direct exposure of sunlight and protect from UV light.

Why DOP[Dioctyl phthalate] banned?

Due to carcinogenic effect for human using of DOP [Dioctyl phthalate] was banned in pharmaceutical company, additionally DOP has the following significant effect which is also the major cause to ban the DOP.

Endocrine disruption

Causes endocrine disruption in male, act as androgen antagonist subsequently effect on reproductive system. Exhibits insignificant levels of reproductive function in adolescent males in Prenatal phthalate exposure. Chromatin DNA integrity and Sperm motility expressively reduce in PVC pellet plant where presence of higher airborne concentrations of DOP. Subsequent study has been proved that the significant exposure of DOP reduce the Chromatin DNA integrity and Sperm motility in men.

Development

Several studies have been shown that significant exposure of DOP has been change the sexual function and development in rats and mice. During pregnancy, excessive exposure of DOP disrupt development and placental growth in mice which cause premature birth, low birthweight, and fetal loss. Advanced levels of anxiety during puberty and hypertrophy of the adrenal glands may arise if excessive DOP exposure occur in neonatal mice through lactation.

Obesity

Intestinal lipases convert DOP to MEHP upon DOP ingestion then MEHP absorbed. MEHP is considered for the obesogenic effect. DOP is the possible disruptor for the thyroid function which have already verified by human studies and rodent studies. Subsequent exposure of DOP is significantly relevant with plasma thyroxine levels and patient with hypothyroidism inclined to to weight gain.

Cardiotoxicity

A minor dose of DOP predominately effect the activity of mice. The duration of the exposure of and clinical dose of DOP has the significant effect of the behavior of cardiac cell at culture. Cell face the slow propagation speeds with fractured wave fronts.

Mix Up, Contamination and Cross Contamination in Pharma industry

Facility, GMP

Mix up

Mix up can be defined as taking something which is not subject to take; taking one thing to another. Taking wrong item unintentionally which can be easily identified such as taking Aceclofenac tablet in place of Metronidazole tablet having different size and shape. Mix up is a mix of diverse item but essentially contaminated. For example one blister strip of batch [A] tablet found with another batch [B] tablet.

Mix up is

Assume wrong item to right thing
Failure to take right action on due time
Mixture of various item/elements
Selection of wrong item
Selection similar product/material/item
Unintentionally taking one thing to another
Wrong selection of desired material
Wrong action taken due to lack of attention

Probable cause of Mix up

Breakdown of processing equipment.
Collation/procure similar packaging/printed material from same vendor.
Conducting packaging operation in other than main packaging belt.
Discontinuous packaging/partial packaging of single batch.
Engaging untrained/partial trained personnel.
Engaging single operator to multiple packaging line.
Failure to follow written procedure for line clearance.
Inappropriate labelling.
Improper segregation of products/item during manufacturing operation.
Improper labelling during dispensing.
Inadequate controls.
Manual operation other than automated system
Multiple product packaging operation in insufficient packaging area.
No barcode/QR code/Identification code
Process validation not properly conducted
Previous batch item such as label, carton, accessories etc. not removed properly
Rejection material handling
Reprocess
Rework
Return of IPC checks item to the wrong/ similar packaging belt.
Repackaging and packaging of similar product/item.
Similar Size, shape, color of multiple products.
Similar design of primary packaging/secondary material.
Similar product line clearance in same time.
Same instruments/apparatus use for multiple item/products/material.
System failure
Wrong labelling

Contamination

Contamination can be defined as the presence of undesirable element, impurity or constituent which infects, corrupts, spoils, makes substandard or makes unhealthy a factory, normal environment, physical body, material, process steps, bulk, liquid, granules, solid etc.

As per US FDA, contamination can be defined as-

Type of Contamination

Non-Viable

Liquid or solid particulate contamination range from 001 and 1000 microns such as smoke, dust, fogs, fumes, and mists.

Viable

Particulate contamination that supports, or consists of one or more live microorganisms such as Viruses, Bacteria, and spores.

Sources of Contamination

Atmosphere
Clothing
Equipment
Fluid
HVAC System
Manufacturing Debris
Premises
People
Processing Operations
Surface
Utilities and Services

Various source of contamination has been illustrated on the respective table-

Contamination of products can be caused by:

Contaminated dress/attire
Contaminated equipment/apparatus/instruments
Contaminated or damaged HVAC system
Contaminated Premises/sites/areas
Individuals, e.g., carrying harmful bacteria
Processing Operations negligibly
Utilities/Services/facilities

Cross Contamination

Cross Contamination can be defined as unintentional transfer of chemical contaminants, microorganism from one person, food, and object to another person, food.

Risk of cross contamination

The involving risk of cross contamination depends on the type/class of contaminant and which product or item will be affected.

The most hazardous contaminant are;

Allergens
Biological item/product/living organisms
Hormones
Sensitizing materials
Toxic materials/Item

Sensitive product for contamination

Administer booster doses
Injections
Prolong period of time
Product Applied to open wounds
Cytotoxic agents

Consequences to Company

Company image crisis
Financial losses
Loss of Company reputation / Adverse Publicity
License cancellation
Market share down
Product Recall
Show cause notice
Shutdown of premises
Vigorous audit by regulatory authorities
Withdrawal of product
Warning letter

Employee Consequences

Financial losses
Jail / Penalty
Reputation loss
Personal Image crisis
Suspension order
Show cause notice
Termination of services

Minimizing the risk of cross contamination

Minimizing the risk of cross contamination from mix up

Allocation and utility connect expertise that are exclusive to the process
Bar coding, QR coding, and RFID of materials and equipment’s
Distinct dispensing areas
Enormous Electronic confirmation of material
Enormous manual check
Isolated raw material staging area with proper labelling
Using of Color coding
Using of Locked and key Stainless steel cages to store APIs with chain of safekeeping
Using of PAT [Process analytical technology, i.e. NIR]

Minimizing the risk of cross contamination from residue carryover

Cleaning validation
Distinct product contact parts
Equipment design for CIP and SIP
Single use product contact parts
Process Analytical Technology [PAT]/online monitoring
Setting of cleaning limit
Set base limits on statistical analysis, science, and risk assessment

Minimizing the risk of cross contamination from Mechanical Transfer

Airlocks system
Cleaning mobile equipment’s/machine in processing room/area
Encompass at the source
Gowning procedures
HSG [High Shear Granulator], Milling and Drying in same suite
Limiting the transfer of compounds between same suits
Room Airflow
Separate work areas to a single product
Sprinkling showers
Wipe down protocols for mobile equipment’s

Minimizing the risk of cross contamination from Air borne transfer

Airlock separation to corridor
Appropriate Room air changes rate
Comprehend the source
Close process systems
Gowning procedures
Room differential pressure
Sufficient Room airflow
Sparking showers

Also read

Cross-contamination prevention during processing in pharma industry

Mix Up, Contamination and Cross Contamination in Pharma industry Read More »

Cross-Contamination prevention during processing in pharma industry

Product Complaints, Product Defects, Product Recalls

Cross-contamination, Before taking steps regarding Prevention of Cross-Contamination during processing, this is very important to know basic about contamination and Cross-Contamination and what is the basic difference between contamination and Cross-Contamination.

Also Read

Mix Up, Contamination and Cross Contamination in Pharma industry

Cross-contamination

Cross-contamination can be defined as unintentional transfer of chemical contaminants (including allergens), microorganisms, or any other foreign substances from person, food, or object to another person, object or food product.

This problem is generally occurs at raw food to RTE[ready-to-eat] products, also occurs between allergen free and allegen products.

Cross-contamination products can cause severe food poisoning as harmful bacteria transfer from RTE products which doesn’t subject to any type processing or treatment on not taken any steps to eliminate harmful bacteria from those foods[RTE]. The best example of cross contamination is transfer of bacteria from raw food to cooked food.

Pharmaceutical products are the highest risk of Cross Contamination. Presence of small amount of antibiotics or trace amount of potent drugs cause severe damage to the patients. Carryover of one products residue to another products is consider the highest risk to the patient.

In the recent year, as per UK MHRA[United Kingdom Medicines & Healthcare Products Regulatory Agency], product contamination is the second to third cause to recall products from the market.

Understanding Cross-Contamination

There are several ways to where cross-contamination can occur:

Equipment to food
Food to food
People to food

Equipment to Food

Contamination can be transfer from pantry equipment & utensils to food staff. This type of contamination can be transfer from improper cleaned equipment or utensils to food items and which is not properly sanitized before each use. Here is some example-

Using of improper cleaned items such as utensils, slicers, knives, grinder, and juicer to prepare food.

Using of cutting and chopping board and use the same knives to cut different food items, such as cutting raw beef and then prepare vegetable salad or RTE food items.

Storing RTE [ready-to-eat] food items in an improperly sanitized container, which was previously used for raw food item such as raw beef.

Food to Food

Food can contaminate by bacteria from comes from other foods. This type of cross-contamination seriously dangerous when raw type foods contact with cooked/finished food/RTE Food. Here is some example for of food-to-food cross-contamination-

Storing raw chicken in the upper shelf of the refrigerator but cooked chicken store lower shelf of the refrigerator where cooked chicken dripping from raw chicken.
Raw meat placed on a on a grill touching another meat that is being cooked.

People to Food

Personnel can be great source of cross-contamination to food items for their inappropriate behavior or lack of training to do the task properly. Here is some points to notify the situation-

Handling of food items just using after the toilet without properly personal clean up.
Touching Raw Chicken and prepare vegetable salad without properly clean up between the tasks.
Handling of apron with wipe hand and subsequently serve foods to individual.
Using of towel to clean the kitchen and further use the towel after dry hand.

How to prevent cross-contamination

Production & Related Area

All type of line clearance should be perform as per approved SOP and related checklist mentioned on BMR/BPR
Avoid similar type of product clearance in same time in side-by-side line.
All the system must be properly validated [Equipment/Machine/Facility/System/Process etc.]
Before starting of any type of product processing, processing product, list of materials, printing materials, primary packaging materials must be contamination free.
Check any type or related starting materials, product residues, products, documents, records, process flow and related documents of the previous products during starting of the new line.
Closed system to be introduce for critical products, if possible close system to be introduce for all type of products handling.
Campaign production may be the best procedure to achieve satisfactory contamination/cross-contamination free products by following appropriate validated cleaning procedure.
During processing, products and direct products contacts part should not be handled with bare hand, use latex free gloves to handle the same with properly spray cleaned with IPA [70% IPA]
During production/processing all type of maintenance work must be prohibited and production/processing to be stop during maintenance activities.
If any area subject to maintenance activities, to restart of the operation, the area must be properly cleaned and maintenance clearance to be ensure from respective department.
Packaging must be properly segregate from processing/filling area, a physical barrier must be introduce to prevent contamination and related operation must be controlled.
Product subject to in process control in production area to be confirm that it should not provide the risk for the product and remaining IPC products must be discard and not to add the processed products.
Production accessories/stationary/liquid item/ink of image printer/other solvent etc. must be kept in labelled container as per their content present in the defined container.
Single line processing to be introduce, never start multiple line/product in the same line
Solution container subject to filling should be properly cleaned before using for filling operation especially for aseptic products such as eye drops, which cannot be terminally sterilized due to container criteria [Plastic container].
Try to reduce bioburden especially for injectable products and remove outer additional/unnecessary/additional wrapping during delivery at the point of use.

Clothing & Hygiene

Appropriate clothing and gowning system to be ensure as per classified area.
Clothing should be different for every shit/working hour/every time before entering the processing/filling area.
Cleaning agents to be use in proper quantity and agents must be contamination free
Clothing and its quality should be appropriate for the process and the grade of the working area.
Daily environment monitoring by particle counter machine, air sampling, settle plate count to be carried out as when appropriate.
During handling of hazardous material/container/liquid/gas, appropriate PPE[Personnel Protective Equipment] should be ensure.
Footwear to be clean properly and each pair of clean shoe to be confirm before entering to the processing/filling area.
Lint free non-shedding cloth to be ensure.
Minimize the exposure of body surface as less as possible.
Repeated wear of same gown in same days must be avoid in processing/filling area.
Separate/dedicate PPE to be ensure for beta-lactam and non-beta lactam, other antibiotics, hormone, generic medicine, cytotoxic etc. products.
Slippery sandal/shoe/loose shoe etc. to be avoid and appropriate shoe to be use such as lint free clothing shoe to be ensure especially in sterile processing/filling area.
Wash the cloth each time before entry of the process room.
Washing system to be separate as per designated area.

Utilities and Service

Appropriate water to be use in pharmaceutical preparations for its targeted use.
Any type of failure regarding water quality test must be notify and action to be taken and production must stop.
Chemical and microbial limits and requirements must be made.
Validation of the water system to be ensure before using water in pharmaceutical preparations especially First and Second phase must be validate and third phase must be ongoing and report should be made.
Water quality must be check before its use.

Steam Quality

PQ[Performance qualification] of steam to be ensure.
Pure steam and industrial steam to be use as when and where appropriate.
Steam must be additive free.
Steam must be contamination free and microbial quality must be passed.

Compressed air/Transportation/Cleaning and related activities

Air quality to be ensure by passing through appropriate filter.
Any sign of spillage/broken/contamination during transport, full quantity must me discard.
All type of processed or partially processed, in-process materials, raw materials, partially packed, finished packed should be properly labelled with Product Name, Batch no., Quantity, Packed by, Packing date, Manufacturing date, Expiry date etc.
Cleaning solvent/materials use for cleaning, lubrication, pest control should not direct contact to the product and suitable grade of cleaning agent to be ensure.
During production, high degree of cleaning and sanitation to be ensure before entering into the processing/production area.
Measures must be taken to prevent cross-contamination and its effectiveness to be ensure.
Processing/manufacturing area for hormones, penicillin, cephalosporin, generic products, vaccine, antibiotics must be dedicate/segregate to prevent cross-contamination.
Transport of Beta lactam and non-Beta lactam antibiotics should not be perform in disclose condition, container must be tightly bind with the appropriate material/stripe. Finished product may be transport with tight pack condition simultaneously.
To be clean/clean label should be properly attached on any containers subject to use or unused with product/material name/batch no.

Cross-Contamination prevention during processing in pharma industry Read More »

Granulation Process, theory of granulation in pharmaceutical company

Pharmaceutics

Granulation, Generally, all of the particles are distributed in irregular manner, when particles create bond between them then granules are formed. To create bond between the particles is not automatic process, mechanical forces are applied to the particles or various types of binding agents are used to create granules. Granulation is simply a particle collecting process where particles are particles create bond between them by compression or with the help of binding agent.

List of binding agent used in pharmaceutical company in granulation process of different material-Various types of binders use in pharmaceutical industry such as-

Natural Binders

Alginic Acid
Acacia
Cellulose
Gelatin
Pregelatinized Starch
Starch Paste
Tragacanth

Synthetic/Semisynthetic Polymer

Ethyl Cellulose
Hydroxy Propyl Methyl Cellulose (HPMC)
Hydroxy Propyl Cellulose
Methyl Cellulose
Microcrystalline Cellulose
Polyvinyl Pyrrolidone (PVP)
Polyvinylcaprolactam
Polyethylene Glycol (PEG)
Polyvinyl Alcohols
Polymethacrylates
Sodium Carboxy Methyl Cellulose

Top Binder Manufacturer

BASF Company
Colorcon
Dow Chemicals
FMC Corporation
Natural Starch and Chemical Company
Penwest Pharmaceutical
Quest International Group
Wolff-Cellulosics

Most of the granules size distribute from 0.2 to 4.0mm and this size may be change based on their mode of use. Granulation process refers to the activity where particles are adhere to form larger and this repeated procedure create multiple particle entities called granules. Granules are formed from series of primary particle, after completion of the process the identity of the primary particle is no longer available.

Objective of Granulation:

1. To produce quality product is the top most priority of the granulation process.

2. To avoid segregation of the ingredients in the powder mix.

-Different size of particle presents in particle mix, segregation mainly occur for the different size of particle with irregular ratio in power mix. Normally two types of particle present in a mix. Normally smaller and coarser particle tend to settle down in the bottom of the container and comparatively large particle store on the top of the container. If granulation process conducted standard way then no particle settle down on the container.

If segregation of the powder mix occur then, tablet compression leads to irregular pattern. Physical criteria didn’t match as per set parameter then directly affect the product quality. To avoid this problem, granulation process to be conduct by using suitable binding agent from appropriate source. Correct proportion of particle mix prevent settle down of the granules.

3. To increase the flow properties of the powder mix.

-Powder contains small size particle, irregular shape or surface characteristics denote poor flow property as the cohesive forces are not dominant here. Cohesive forces to be increase to get better flow property of powder. If cohesive forces is not dominant, particles are generally settle down to the bottom of the container.

4. To produce even mixtures.

5. To control powder density.

6. To produce dust free preparation.

7. To remove poor content uniformity.

8. To increase the compaction characteristics of the Mix.

9. To seizure and fuse small quantities of active material.

Mechanism of Granulation: How granules are formed

In pharmaceutical industry, granulation is the key step to prepare any type of tablets, pellets, powder for suspension and related powder products. So this is very important to know how to develop gangues from powder. How granules quantity may be develop and how we can overcome associate problem during granulation.

This is very important to form bond between powder particles as they adhere between them form particle-particle bond. The bond formation to be adequately strong so that they can overcome the breakdown tendency during subsequent handling.

Type of bonding mechanism: Five Types

Solid bridges
Mobile liquid films
Immobile liquid films
Mechanical interlocking
Attractive forces between solid particles

granulation, bonding mechanisms between particles

Methods of Granulation

Wet Granulation

Dry Granulation

1. Adhesion and cohesion forces in immobile films

In the presence of sufficient liquid in powder mix to form thin and immobile layer then inter-particulate distance will be reparably decrease and subsequently contact area between the particles will be increase.

Due to more surface availability bond strength between the particles will be increase, as per Van Der Waals force of Attraction, the forces are proportion to the particle diameter and inversely proportional to the separation distance.

During Dry Granulation, the pressure will increase the contact surface between the layers and subsequently decrease inter-particulate distance in the result; this will contribute the granule strength.

In the presence of highly viscus solution of adhesive, the thin, immobile layer form which will strengthen the bond between the particles compare to mobile films.

2.Interfacial forces in mobile liquid films

In the time of wet granulation, sufficient liquid is added to the powder and this liquid distributed around and between the particles. Sufficient liquid help to exceed the immobile layer to convert into the mobile film. Several types of water distribution systems which has been demonstrate here-

granulation, water distribution in granules

Pendular Phase:

During this phase, lens shaped rings of liquid hold particles where as this phase generally occur low moisture condition in the powder mix. Surface tension forces in the liquid-air interface and the hydrostatic suction pressure in the liquid bridge cause adhesion.

Funicular Phase:

This is the intermediate stage between the pendular and capillary phase when air start to displace between the particles then the particles arrange funicular phase. After completion of the intermediate phase- Funicular Phase then capillary phase visible where air completely displace/remove between the particles.

Capillary Phase:

As all the air remove between the particles, the Capillary Phase arrive and the entire particle held by the help of capillary suction in liquid-air interface at the granule surface. Tensile strength increases almost three times in moist granule in capillary and pendular phase.

The total moisture content plays a vital role in the phase of the power bed where total moisture content is the key factor, if separation of the particle can be decrease capillary phase may be reached easily which is the most desirable phase in granulation.

Droplet Phase:

This is the most undesirable phase in granulation. This phase is important in granulation at spray drying of suspension.

Mechanism

During the wetting and mechanical handling of particulates, the Agglomeration, granulation and pelletizing processes is greatly involved. If we increase the wetting and mixing, then open and porous agglomerate structure changes into more close and grain like granule structure. The control of moisture is the main factor in particle engineering, energy input require achieving desired structure of the granules.

Generally wet bridges considered as temporary structure as the moist granule will be dried in the certain period of time. This phase is measured prerequisite for the creation of solid bridges which is created by adhesive present the liquid.

3. Formation of Solid Bridge after Evaporation:

Solid bridges:

First, solid bridges formed by the help of adhesives present in the liquid or dissolving materials present in the granulating liquid. This can be formed in several ways-

Partial melting
Hardening binders
Crystallization of dissolved substances

Partial melting

Most of the low melting substances present in granulation process melt down by applying of pressure in the dry granulating process. Particles are readily bind with one after another and crystallization develop as the applying of pressure.

Hardening binders

By the help of adhesive which add to the granulating solvent, the liquid form liquid bridges, and upon drying the adhesive harden the phase and form solid bridges and bind the particles together. Common uses binders like PVP[ Polyvinylpyrrolidone], CMC[Carboxymethylcellulose], starch etc. plays the vital role.

Crystallization of dissolved substances

The powdered ingredients use in the solvent use in wet granulation may partially dissolve the powdered ingredients. At time of drying of granules, crystallization of powder material occur and act as hardening binder.

Drying rate of the granules are greatly hampered by the size of the crystals create in the bridges, larger the particle size will require more drying time and vice-versa.

4. Attractive forces between solid particles

There are two types of attractive forced which can operate between particle in pharmaceutical system beside the liquids and solid bridges formed by binding agents, demonstrate here-

•Van der Waals forces

•Electrostatic forces

This to me mention here that the Electrostatic forces don’t contribute to the final strength of the granules moreover this is important in the powder cohesion and initial formation of agglomerates e.g. during mixing. This force may be increase during when grain sizes decrease.

Van der Waals forces having four orders of magnitude which consider the greater compare to electrostatic and add great strength to the granules. When the distance between adjacent surfaces decreases then the magnitude of these forces increase. Dry graduation process is achieved by applying the forces to the particles.

5. Mechanical Interlocking:

mechanical interlocking phases that the adhesion occurs when adhesive properly penetrates into the holes, crevices and pores, and other loopholes of the adhered surface of a substrate and which locks mechanically of the substrate and must have the right rheological properties which will help to penetrate pores and other opening in due time.

Adhesion

Besides adsorption, there are Four other mechanisms of adhesion has been projected. The first mechanism is mechanical interlocking, which occur when adhesive drifts into the pores in the adhered surface. The second mechanism is interdiffusion, result when liquid adhesives are subject to dissolve and diffuse in the adhered materials. Adsorption and surface reaction projected to third reaction.

Mechanisms of Granule Formation:

a)Nucleation

Particle with particle[Particle-particle] contact and adhesion for liquid bridges is the key factor in the Granulation process. Particles are joined together to form pendular phase. Application of agitation, desifies the pendular forms and form the capillary phase and this form act as nuclei for granule growth and the next phase.

b) Transition

Nuclei can grow in two ways e.g. Single particle can be added to the respective nuclei with the help of pendular bridges, another possible ways, where two or more nuclei combine and form big nuclei. After completion of the phase, upon application of agitation to the bed the combined nuclei reshape and this phase can defined as a condition where large number of small granule present in greater range of distribution.

c) Ball Growth

When agitation continued, granule coalescence continue produce unusable, over-massed system where this phase greatly depend on the liquid quantity and material properties.

Coalescence

In this stage, two or more granule join and form large granule.

Breakage

Granules subject to break into fragments and this fragments adhere/join with other granule form a layer to the persisting/living granule.

Layering

Addition of the new powder mix with the existing granules, the powder mix adhere with the existing granules and form a layer over the existing granule and increase the granule size.

Abrasion Transfer

If agitation applied to the granules bed, then agitated granule leave abraded materials, which further add to the other granules and accelerate the granules growth.

mechanisms of granule formation, ball growth

Factors Affecting Granulation Methods

Liquid Requirement

In high shear mixers, the liquid requirement margin is narrow to granule growth and produce over wetted mas. For the intensive wet mass and densification of the granule less liquid requirement assume compare to low share mixers. Impeller rotation speed is another factor for liquid requirements and resulting evaporation of the solvent specially water in the binder solution. In high-shear mixers, intense agitation results temperature rise and subsequently loss of solvent for evaporation.

Theory of granule formation in general

At the early stage of studies near at 1950’s, it was stated that the granules growth by coalescence and limiting moisture content and further mechanical agitation modifies granule shape.

The modern science has divided the process in four major class for granulation process such as-

Powder wetting and nucleation
Granule coalescence or growth
Granule consolidation
Granule attrition or breakage
Granulation is a complex combination of these subsequent processes.

Pharmaceutical Granulation Technology

The word “granulated” derived from Latin Word ‘‘granulatum,’’ denote “grained”. Granulated materials come from two way, by “size enlargement” of primary particles and “size reduction” of dry compacted materials. Now a day’s granulation technology has been widely applicate at mining, agrochemical and coal industry.

In these industries, agglomeration techniques mainly used to reduce dust and this technique provide easy handling and boost the material’s decisive effectiveness.

In the year of 1843, W. rockedon invent the tablet press and subsequent modification and patent was done by J. A. McFerran[1874], T. J. Young (1874), and J. Dunton (1876) in USA which tremendously hit the granulation technology in pharmaceutical technology. The granulation technology was further reshuffle at 1970 when high speed tablet and capsule filling machine with PLC was invented.

The regulatory bindings such as content uniformity/blend uniformity facilitate to produce desired granule characteristics for pharmaceutical company. On the other hand, continuous uniform materials/granule flow must be ensure for high-speed compression and capsule filling machines. Granulation is the best example of particle design. The attributes of the granules controlled by formulation and the process respectively.

Granulation method can be divided into two major group as Wet granulation where liquid use to bind primary particles and Dry Granulation where no liquid is used.

The reasons for granulating a pharmaceutical compound are demonstrated as follows:

To decrease dust.
To densify the materials.
To increase the appearance of the product.
To simplify metering or volumetric dispensing.
To improve the flow rates and rate of uniformity.
To escalation the uniformity of drug dissemination in the product.

Processing steps of drug substance can be easily achieved avoiding granulation steps. By using a direct compressible excipients like MCC[Microcrystalline Cellulose] which was introduce in 1970s in a blender then compress tablets or filled hard gelatin capsule. This is very efficient method for cost effective method, faster process time and simple process steps.

In this technique, low dose of drug substance show reverse criteria, uniformity of drug substance is not possible/ accurate result may not found. The sample need to collect from the blender and time require performing the test to get satisfactory result. A newly introduce PAT[Process Analytical Technology], online measurement of ingredients made possible. FDA also release latest guideline about PAT.

Beside content uniformity, there are numerous cause to avoid direct compression technique for wide range of products where drugs substance need to densified to reduce size and physical criteria such as disintegration, hardness, friability need to meet.

Another approach like traditional spray-drying process become popular in day to day to produce drum to hopper granulation avoiding conventional granulation process. This is very suitable for OTC drug which generally produce large amounts.

In pharmaceutical company, some of the products/drug substances are moisture sensitive which can’t subject to direct compression, then roller compaction is the best method to compress this product.

Before introduce of high shear-mixer, low-shear mixer was the first priority, shear-mixer generally use in in wet granulation their efficient, reproducible and modern process control capability. High-shear mixers enhanced with new technologies as one-pot processing and subsequent drying using gas stripping/vacuum or microwave.

The most versatile featured Fluid-bed processors has been using in the pharmaceutical industry over the last 35 years though initially it was introduce with single dryer, now enhanced with multiprocessor to coat particles, pelletize, granulate and drying. Now combination of high-shear mixer for granulate and fluid bed as dryer is the most popular method in granulation technology.

Theory of Granulation

Wet granulation technology is especially considered in size enlargement where small particles are compacted; agglomerated or else brought together to form larger particle comparatively permanent structure though the original particle can be distinguished. Size-enlargement and Granulation technology has the wide range of application in various industries like pharmaceutical, fertilizer and detergent production factory.

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ALCOA Plus and ALCOA its importance in data integrity

Documentation, GMP

ALCOA Plus [ALCO+] is the most powerful and sharp compare to previously introduced ALCO has the great importance regarding data integrity in pharmaceuticals company. Data security is the provocative questions is the pharmaceutical and related healthcare sector. Adulteration of data leads to serious health hazard to the end user.

All of the regulatory authority of healthcare related sector has taken their active place against data Adulteration. Data must be accurate, No an Adulterate data is accepted at any situation. Everybody desire the right data at any time any place. Data violation define the serious non-compliance of GMP.

ALCOA is abbreviate form, which indicate Attributable, Legible, Contemporaneous, Original and Accurate. In the period ALCOA, extend to ALCOA Plus[ALCOA+] by addition of Complete, Consistent, Enduring and Available.

In previous time all of the GMP compliance company use ALCOA, now they use ALCOA Plus concept to capture its place the most dependable tool for data security. Most of the GMP oriented company taken the tool for data security and data quality. ALCOA Plus ensure the data security and Integrity. All of the major GMP authority choose ALCOA Plus and implemented their respective directive. ALCOA determine the all-out of data quality. UK MHRA, FRA, TGA, WHO purely involved in data security, quality and data integrity.

The ALCOA and ALCOA Plus concept has been illustrated for better understanding of data related matters.

1. Attributable

Attributable define that the data must be easily traceable, so that anyone can identify that a specific person has collect the data in define time and noted down correctly. To correct any type of error regarding data recording, correction to be made in such way that anyone can read the error data and the corrected data easily. Reason must be noted down with specific signature and date.

Any document subject to data recording must be contains specific field where anyone can note down his/her name then signature and date option. Specific must contains sufficient space so that anyone can record data easily. If any alteration required, put a straight line over the error data then write down the actual data with signature and reason. If space is not available the put an asterisk mask then put another asterisk in a place where sufficient space for signature and reason recording.

2. Legible

Most of document in pharmaceutical company subject to data recording in specific field of a specific document. Entered data must be readable. Data which can be easily readable defined as legible data. Unclear data create confusion to reader and result of a specific test or critical point create unwanted error. The personnel who are responsible to entered data must be trained on GDP [Good Documentation Practice].

Permanent ink or indelible ink to be use to record the data, ball point pen to be use instead of fountain pen. Different color ink to be use to identify the recorded data easily i.e. if the printed document is black color then blue color ink pen can be use to record the data. Similar color ink pen with printed document create delay to identify the specific data.

The input data must be clear and easy to traceable who is responsible to input the data. Data should be entered in such way that no visibility of data subject to misunderstanding to the reader. Anyone who is going to deal with the recorded data must be comfortable with it.

3. Contemporaneous

All the data subject to recoded in document must be recorded on time indicate contemporary data. All data must be entry on the specific field of the document, just after completion of the work with signature and date, if any error occur during data recording then GDP to be follow to correct the issue.

If any correction identified after recording of data in the later date then actual data to be entered data and time with signature on that date. No advance or later data entry is not indicate cGMP culture at your firm. On time data recording is the pre-requisite of the compliance.

A person on the specific date may be absent or leave or fall any unwanted situation, if he fail to entry the data cause serious non-compliance so in time data entry to be ensure. If require, a training session may be conduct to emphasize the importance of contemporary data. Contemporary data culture on the document define that your firm is up to date and ready to face any compliance audit both local and global.

4. Original

To protect the data integrity, the original record must be preserved in such way that it can be preserved till it expiry. Batch document and some documents to be kept additional one year from its product expiry but validation document lasts company life so all type of document preservation may not same. A policy to be develop to preserve the documents and record.

Some document need to duplicate in multiple copy, in this case the creator must ensure the authenticity of the multiple copy with the help of site quality head other that QA documents. A controlled copy seal may be introduce for this issue.

5. Accurate

All data subject to record in the document must be error free. Data can’t be change at any cost. Alteration of data is strictly prohibited. Print out any data create its accuracy, hand written or manually input data, subject to change or alteration. If any facility declare to print out option then manually input data is totally invalid. You must follow the machine print out. To maintain the data quality is the big compliance issue.

Alteration of any digit in manually define the serious discrepancy data quality. It is undesirable to may any digit to next digit or similar digit. Data rounding may be accepted as per USP method but it is not mandatory to follow.

6. Complete

If it’s declare that the data is complete, then it means no alteration, deletion, only original data has been taken from its actual documented time. Incomplete data create haphazard situation to identify the original. Incomplete data recording leads the false result. Data to be record at actual from its predefined time as mention on the document.

If any document declare that you have to record data in 45 minutes interval then you have to record the data at 45 minutes interval not 50 or 60 minutes interval. If you note/record data other than 45 minutes create incomplete/false data. This data is purely incomplete.

7. Consistent

Data must be consistent, chronologically arranged in appropriate time frame. Data should be record in in such way that any audit can rely on it. GDP practice is the best way to record the data. Series of data that is chronologically organized define the data is more consistent and reliable. A reliable data can face any type of GMP audit due to it provides best data integrity.

Most of the pharma company face serious non-compliance at regulatory audit for data integrity. If your firm confirm data integrity then you can create best GMP culture at your firm. To maintain data integrity is the prior conditions of the cGMP.

8. Enduring

All type of material is not suitable for data recording, specific paper to be introduce for specific data recording. Data to be record in such material that it can be traceable after a period of time. Generally long lasting material use for data recording. You should take care about readability of data after a specific period of time based on its impotence.

Usually better quality paper use to record validation related document as its last till company life. Regular uses document like batch production record may be record in general usage paper as its last maximum 3 to 5 years including shelf life plus one year.

Document subject to destruction, proper recording to be marinated as it can be easily teachable. Approval must be taken before proceeded any type of destruction related activities.

9. Available

Data should be kept in a specific place where you can easily find it or it is available as when required. It should be keep in a secure place and access must be limited. List of personnel must be define to access the specific area. Data plays an important role when any organization want to take any decision based on previous history. By this time you have to make it available on that time so you have to keep it in right place. All type of future reference backed by data history so you must pay attention to secure your data.

This all about ALCOA and ALCOA Plus

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Technical person, How to become a Technical person

Personnel

Technical person

Technical person, a person having STEM degree or person possess degree in lab-based science, technology, mathematics and engineering.

People who are attained STEM degree contain common set of traits. These traits make him ideal scientist, technologist, mathematician and engineer.

What do you mean by STEM?

STEM, this term often found in university advertisement, campaign, website, leaflet etc. but most of the people is not sure what does it mean. Here is the solution-

The term STEM define Science, Technology, Engineering and Mathematics and relevant subjects that are all under these basic subject.

Due to these subjects are not straight forward so series of subjects are undergo these subjects. Different terms are used in place of STEM as STREAM and METALS but the term STEM is more widely used.

Though these subjects are widely distributed but huge volume of vacancy found the respective field. From its beginning of STEM, various types of institutions are try to attract the students/people. STEM courses are the top most priority of the most of the counties to remove the shortfall.

STEM subjects the best option for the people who are searching for a longtime to be a resident to the other country/ immigration to expected country. This also beneficial for all type of students who want to study in higher level in different countries.

What are STEM subjects?

The STEM subjects [Science, Technology, Engineering and Mathematics] is not standalone, various type of subjects are closely related/derived from STEM so they are also STEM subjects. Here is the list of some STEM subjects-

Aerospace engineering
Astronomy
Biology
Biochemistry
Chemistry
Chemical engineering
Civil engineering
Computer science
Electrical engineering
Mechanical engineering
Mathematics
Physics
Psychology
Statistics

This list is far more extensive, the list will be more distributed based the basic criteria. This list my helpful for someone who are really searching for STEM subject and he will get som idea about the pattern of the STEM subjects.

The career prospects of some the subjects is more exclusive such Astronomy leads to the straight forward career patch than others subjects which tends to multiple career facility. Most of the STEM related subjects tends to more valuable sector such as Finance, Accounts, Aerospace, Cinema, Special Effects, Design and communications, Sportswear, consistency, Farming, Telecoms, Energy, Pharmaceuticals, Healthcare, Medical device etc.

What is the current situation in the practical field?

The history says, most of the STEM degree holders are male compare to Female. Introducing women in technical field is not satisfactory, the completion is less to female. More than Eight times male are more involve than female in STEM subjects related activities.

About 12% women are graduated in STEM degree; only 3% engage in practical field others are tend to alternative sector or stop to practice. The gender balance is dominant tend to pay gap in STEM field. More than 30% pay gab observed in in Australia at 2013. A remarkable initiative to be taken in this field to fill up the gender gap in STEM related subject.

How to become a Technical person?

1. Take post-secondary science classes

To enter into the professional STEM subject program, two years of college education is required. Most of the STEM subject’s candidate take 4 years of post-secondary education and achieved bachelor’s degree before applying any Doctoral program. As a STEM subject student you have to meet the requirements of the respective organization to get admitted for Doctoral Program.

2. Pass the Admissions Test

To enter into any doctoral program you have to pass the specific test. The specific exam includes various types of questions such as writing, critical reading, quantitative reading, critical reading, different type of process based on your STEM subject including one writing prompt. Exam occur all around the year, at least six times a year.

3. Earn a Degree of STEM subject

After passing the required test, you can apply for for Doctoral program of STEM subject, it may take 2 to 4 years based on subjects. If you want to gain practical knowledge, choose a program with 1 year internship.

4. Cultivate essential skills

To be successful in your next professional life then think deeply about your subject oriented skills, initially basic computer skill is required to run various type of thesis program and assignment oriented job.

5. Attend In plant Training

If you want to work in a factory related job/any job, you can apply for in plant training. Various types of organization offer this type of facility. If you select a program with 1 year internship, please escape this step.

6. Apply for license to practice in your state

You may face to license process based on your state require requirement. To start your career as profession STEM subject oriented job, license is mandatory in most of the state. Here you may face a single or multiple exam to prove your competency of the respective subject.

7. Pre assessment for interview

An interview process may arrange where SME[Subject Matter Expert]/ Assessors may present to conduct an interview. Number of SME/Assessors may vary state to state.

8. Attend interview

A representative will call you to attend an interview session based on your application with specific time and place.

9. Complete required training

If you want to work independently then you have to complete several training program based on your subject. Most of the SYTEM subject holder choose one or two years training program and on the job training program to facilitate his professional activities.

10. Responsible Technical person

After passing the exam and complete the required training program you can work independently or you can join a suitable position in any organization where you can create a value for yourself.

Also Read:

Qualified Person, How to become a Qualified Person?

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Qualified Person (QP), how to become a Qualified Person?

Personnel

Qualified Person (QP)

Qualified Person (QP), is mainly responsible to confirming/assuring the quality of certain batch of pharmaceuticals products. So this is very important that a Qualified Person (QP) must be in depth understanding of the pharmaceutical manufacturing, quality control and overall activities of the marketed products.

Qualified Person (QP), is the responsible person to certify a certain batch of pharmaceutical product prior to use for trail purpose or to send in the distribution channel for marketing.

This is not mandatory to understanding the manufacturing practice/process/procedure accurately but he must be understand the critical factors which may affect the critical quality parameters, safety and distribution/supply chain of the marketed products.

Qualified Person working area:

Most of the Qualified Person[QP] working in different pharmaceutical companies in various role mainly in product releasing activities but they also involve in national health sector, in such type of departments which hold different manufacturer authorisation to create various medicinal products mainly use in investigational purpose.

How do I become a Qualified Person?

1.0 Find a sponsor

A sponsor to be find out regarding individual guidance, training, prepare for final assessment, sponsor reporting about your eligibility to act as a Qualified Person[QP]. The sponsor also verify your application form signature required in various section of the application form.

Eligibility of Sponsor:

The sponsor must be the member one of the three professional body [The Royal Pharmaceutical Society, the Royal Society of Biology and Royal Society of Chemistry] and he must a QP [Qualified Person]. If your sponsor fail to meet criteria, then the sponsors form must be countersigned by the QP [Qualified Person] who will responsible to acting this issue about your engagement.

The sponsor must be involve in practicing QP who is known to you and he professionally known you in qualified period experience[1 year for Pharmacist and 2 Years for other professionals]. If you didn’t manage it, then you can use a Quality Assurance Line manager provided the report and countersigned by a QP.

Your sponsor is projected to:

Confirm that you have the sufficient knowledge of the subject that covered by the study guide. Certify the adequate experience.

A sponsor is actually a mentor for you. He will help you regarding your preparedness of the assessment, he will guide you to attain your success. He will confirm you that you possess the sufficient knowledge for final assessment. He will trained you in every step for apply the final assessment. Your Sponsor will provide you the necessary study guide and confirm that you possess the essential knowledge, skill, experience and personal attribute to act as QP[Qualified Person] at actual.

Role of an active sponsor

Role of the sponsor is the key to success of the applicant. This is very important for the applicant to find out an active sponsor because a sponsor is always involve the applicant training and application process. A sponsorship is always appreciated if role and responsibilities perform on great care. Regular interaction with the applicant is very important and this activity will be consider as mentor.

The sponsor Form and the application form is the first step of assessment process due to these two forms provide the documented evidence regarding employee background. The well documented application provide the positive impression to the Assessors.

The sponsor must have the experience and knowledge about pharmaceutical manufacturing, Quality Assurance and GMP[Good Manufacturing Practice]. Well conversant and up to date of the legal framework of EU and UK. Better understanding and relationship with professional bodies of MHRA & VMD [Medicine and Healthcare products Regulatory Agency & Veterinary Medicines Directorate].

The code of practice, role and responsibility of QP to be known including Study Guide and practical experience requirements. It is top most priority to be well familiar with the pharmaceutical business especially in Research and Development, production, Quality, Marketing and distribution.

An active Sponsor must possess good inter-personal skills and well communicator, having good contacts outside the company will add extra benefit. A better Sponsor will work as mentor who will provide the guidance to the aspiring applicant including positive direction.

Regular interaction is the key factor of the success, sponsor may communicate with applicant via various type of communication method [FB Messenger, WhatsApp,SMS,Emailing etc.] if unable to direct contact. Sponsor should monitor the daily activities of the applicant and prepare a progress report.

Sponsor’s report

Before submitting the application a sponsor form must be submit with the application. An application will not accept/review without sponsor report. A sponsor report must be different from applicant, sponsor report may not represent the same as applicant form.

A honest review is always create positive impression to the applicant. A sponsor report well be well described about the candidate. Every single details will be mention here. Applicant strong side as well as weak side, strength, personal attribute, development field need to mention very clearly.

The report is a key part of the sponsor’s input and it is not sufficient for you to simply provide a declaration of belief that an applicant complies with the requirements. It should be a critical and honest evaluation of the applicant’s technical and professional knowledge. It should also include information on the applicant’s personal attributes, including his or her strengths and weaknesses or areas for development.

A sponsor may indicate the following criteria of the Applicant but not limited to-

Attitude
Communications skill
Extracurricular activities
Flexibility
Hobbies
Open Mindedness
Organizational behavior
Peer coworker relationships
Planning and organizing skill
Professional integrity and ethics
Problem solving capacity
Verbal skill
Reliability
Working under pressure

This very important to notify the every single points on the report. Application primary assessment may be late based on the points and further clarification may be asked. Sponsor need to confirm that the applicant has gained the proper knowledge and experience in the Manufacturer’s Authorization and Manufacturer’s Authorization number with issue date to be mention with the application. A sponsor must declare the direct the working experience with the applicant. Different report will claim for multiple establishment.

2. Gain relevant experience

To be a QP[Qualified Person], a person shall be possess a certificate, diploma, or other evidence which can prove his formal qualification evidence which achieved after completion of University course, covering a duration at least Four Years of theoretical and practical studies one of the listed scientific discipline:

Chemistry
Medicine
Pharmacy
Pharmaceutical chemistry
Pharmaceutical technology
Pharmaceutical biology
Veterinary medicine

The minimum duration of the university course may be three and half year, where the course followed the theoretical and practical training duration minimum one year and training period will be six month in a pharmacy open to public collaborated by examination at university level will be preferred.

When two university course declared equivalent and one course extend to Four years but other course extend to three years then the three years course will be treat as diploma, the course shall include the listed basic subjects at least:

Analytical chemistry
Experimental physics
General and inorganic chemistry
General and applied biochemistry (medical)
Microbiology
Organic chemistry
Pharmaceutical chemistry
Pharmacognosy
Physiology
Pharmacology
Pharmaceutical technology
Toxicology

The QP[Qualified Person] experienced in practical required two years in authorized manufactures and experienced may be reduced to One Year where the university course extending to Five years.

Overall, at least Two years expected is required in one or multiple facility which produce medicinal products but if you are pharmacist, you need only one year.

3. Apply through your professional body

The eligibility of QP, he must be the Pharmaceutical Scientist or Associate or Fellow or member of RPS[ Royal Pharmaceutical Society] who has qualified on the basis of formal course of study lasting not less than three years in fulltime or equivalent.

Minimum One year of practical experience is required for pharmacist, if anyone want to apply for QP eligibility but not registered a as pharmacist recommended to contact with QP officer for advice prior to apply.

If your Sponsor is satisfied that you are ready to apply then submit the application form with required fee [£700, may be change anytime], sponsors report and countersigned copy of your own certificates.

4. Wait for your initial assessment

If you application fulfill the requirement then QP officer will confirm you that your application has been received. Your application will be assessed be the designated assessor if the result goet to positive then you will be invited for interview session.

5.0 Attend your interview

Your interview will be held on London physically if situation is normal. Sometime virtual interview may held based on situation, QP officer will confirm you about this issue. If you passed the interview then you will be listed as QP person at your professional body.

Role and responsibility of QP

All of the pharmaceutical manufacturing authority and regulatory body ensure that the end user [Patients] are safe and the medicinal products meets its predetermined specification for sale or supply and confirm the basic requirements for safety, quality and efficacy.

In a pharmaceutical company a QP plays a vital role certifying the batch confirms the predetermined specifications and its can be released for sale or supply or trial.

QP is responsible to confirm that each manufactured batch has been checked in compliance with the laws in specific certifying authority.

QP role and responsibility irrespective where the product will be sale/distributed/used.

QP to be understand the demand of specific Authorization and confirm that PQS[Pharmaceutical Quality System] in place and satisfactory for the purpose.

QP must understand the relevant steps of pharmaceutical manufacturing steps before certifying the specific batch.

Must be full understanding of EU GMP guideline.

QP must have decline to certify the specific products which process and procedure is unknown to him.

Career prospects of QP

The Career is widely distributed for the QP in various types of pharmaceutical industry as well as other designated industries who are involving in manufacturing of healthcare related products undergo to regulatory bindings. In pharmaceutical industry a QP can work in production, marketing, quality control, product development, quality assurance, project management etc. areas.

Resources to become QP and formal application process

Application form

Guidance notes for applicants and sponsors

Study Guide

Code of Practice for Qualified Persons

Sponsor Form

Download all Resource Here:

Click Here

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