Clean room classification In Pharmaceutical Industry Guidelines

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Clean Room Classification Pharma Industry

Clean Room Classification in pharmaceutical Industry how it is done?. What is a clean room in Pharmaceutical Manufacturing?. Which are the different requirements of clean room class in pharmaceutical manufacturing ? Particle count and Viable Count requirements of different grades of Clean Rooms. Clean rooms in pharmaceutical industry are classified by three Standards. 1. ISO … Read more

Restricted access barrier system

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Restricted access barrier system RABS technology for sterile dosage form manufacturing and filling.

Sterile dosage form is required to maintain its sterility and it directly depends on the movement of personnel working in the aseptic filling area. Slightest movement of personnel can shed a huge number of particles in the filling area and there will be a risk of contamination of product being filled.

Machines are made up of SS 316 and once cleaned and sterilized can maintain the sterile environment unless it is disturbed by manual interventions.

Manual interventions and man movement is required to control very critically to maintain the sterility of product being filled in an aseptic filling area.

One method to achieve the enclosed aseptic environment with limited handling is use of isolators, isolators isolate the critical activity inside a contained environment, isolators are provided with heap filters which are capable of maintaining sterile environments and controlled particle count in critical areas.

But one disadvantage is that it cannot withstand a bigger area and for longer duration, it is required to be cleaned and disinfected frequently.

Therefore, Restricted access barrier system technology is one that takes care of above concerns, once cleaned and decontaminated, sterilized it can maintain a class 100 and sterile environment for longer duration.

The walls of the RABS are rigid and hermetically sealed with the filling area which actually separates the aseptic filling area from the outer area with a physical barrier.

The RABs are provided with UV light and Gloves at intermittent location to facilitate handling of product, adjusting weights during filling and setting parameters on the filling machine. Additional ports for media plates for environment monitoring inside the aseptic area during filling activity or during routine monitoring are provided, glove integrity testers are also provided so that before start of the aseptic filling activity it can be assured that there is no leakage in the gloves.

Restricted access barrier system RABS are very useful in sterile dosage form manufacturing and filling, with the help of RABS actually the risk of product getting contaminated due to manual manipulations can be eliminated completely.

 

Ristricted access barrier system
Ristricted Access Barrier System

Design of Restricted access barrier system (RABS) include following aspects.

1)Rigid wall enclosed, with finished surface to prevent accumulation of particles, and can be cleaned and decontaminated easily.

2)Unidirectional flow units with HEPA filtered provide filtration of air inside the critical area and help maintain the clean air class required for sterile dosage form.

3)Facility to do sterilization in place of machine parts that come in contact with the product, its primary containers and closures.

4) Facility to do sterilization of parts which cannot be sterilized in place, but can be autoclaved and transferred inside the RABS without compromising the sterility of the area and aseptically assembled again.

5) Facility to do aseptic manipulations during filling.

6) Facility to introduce inside RABS the media plates and indicators, air samplers and place them inside the RABS, without compromising the sterility of the environment inside the RABS.

There are two types of RABS based on the additional UDAF facility and partial and complete separation from the outer area with barrier walls.

1)Passive RABS utilizes the room’s air filtration system. When the outer environment is completely separated by walls it is called as passive closed RABS.

2) Active RABS is provided with additional UDAF inside the RABS. . When the outer environment is completely separated by walls it is called Passive closed RABS.

Gloves and gauntlets are sterilized and fitted aseptically without compromising the sterility of the environment.

It is required for a RABS system to have in place a sterilization procedure for all non-contact parts with a highly effective sterilizing agent which includes sporicidal.

Validation of Restricted access barrier:

Validation of Restricted access barrier RABS is done by doing the following activity.

Risk evaluation should be done for RABS and a risk based approach is required for performing the validation of RABS, following points are considered during the validation of Restricted access barrier system.

1) Particle count inside the RABS. Air velocity test, HEPA filter leak test, flow pattern.

2) Pressure differential to maintain and establish documentary evidence. Pressure inside the RABS should be greater than the outer area.

3) Inner surface of RABS to monitor for microbial load, with swab test.

4) Media fill to be done for consecutive events, to establish the environment and the procedure adapted for sterilization of contact parts are adequate.

What is 483 observation of USFDA

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What is 483 USFDA observations? Detail information issued by the US FDAs 483 observation form.

US FDA is world one of best pharmaceutical regulatory agency, when it conducts any inspection and observe any discrepancy or violation with respect to the good manufacturing practices guidelines issued by US FDA, it provides the observations in a format which is predefined and the format number given by US FDA is 483, this format describes in details. The observations are given in this format when the inspector’s opinion confirms that the firm is in violation, the observations are very specific.

1) Is the observation regarding drugs or biological or medical devices, etc.?

2) Which manufacturing site it is the US FDA gives site ID to every manufacturing unit from which food and drugs are exported to the United states.

3) Reference number form the Guidance document, that is 21 CFR part211 is for drug products.

4) Short description of the observation.

5) Detailed description of the Observation.

6) Comment from the inspectors, and what they expect to be followed.

Do all observations are cited in Form 483 issued by the US FDA?

Only selective observations which are observed by inspectors are cited in 483 observation of USFDA, all observations are discussed by inspectors with management of the pharmaceutical company during closure meetings.

What is the purpose of giving 483 observations? What should be done after 483 Observations are received?

FDA expects that the company will take care of the violations observed and put in place corrective and preventive action so that these violations do not occur again.

A communication is required to provide to US FDA about the corrective and preventive actions taken, details of steps taken to meet the compliance, in predominant and as soon as possible.

USFDA 483 observation report is not the action taken by FDA against a pharmaceutical manufacturer, in 483 only few observations are cited, while all the list of observations is mentioned in establishment inspection report.

FDA doesn’t take any action based on only 483 observation forms, but the detailed establishment inspection report and the response from the pharmaceutical manufacturer all together are considered before taking any final action by the US FDA against any pharmaceutical manufacturing company.

Basic principles of clearing the US FDA audit without any serious observations are as follows.

1. Read the Good manufacturing practices, guidelines issued by US FDA, guidance documents that is 21 CFR for respective dosage and for respective guidelines like, sterile dosage form, Quality systems, etc.

2. Write SOPs of Production, operation, and maintenance, Quality assurance, Quality control, by keeping in view that.

A) Whatever is written in SOP is practicable and can be followed, and that fulfills the requirement of Guidance documents.

B) Train the manpower to follow the written procedures, if any deviations file the deviation report, if any changes to do it through Change management system, if any market complaints or quality issues arise, investigate properly, derive root cause and implement the corrective and preventive action to eliminate the root cause completely.

C) Manpower should be trained to follow the written procedures exactly, there should not be any deviation after this.

D) Maintain cleaning procedures and hygiene.

E) Documentation without any overwriting or any manipulation or and documentation must be written as the work happens there and there concurrently, without causing any delay.

F) All the principles of maintaining Data integrity must be followed.

These are a few simple steps, and honesty is at the heart of everything that the US FDA wants from every pharmaceutical manufacturer across the globe. It’s not at all difficult to maintain and follow, if your principle of doing business with the US is honest.

483 observation of USFDA

Source:

https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/inspection-references/fda-form-483-frequently-asked-questions

How to Investigate Out of Speciation results

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What is OOS in pharma, how to Investigate Out of Speciation results. 

OOS is an abbreviation of term “out of specification” the specification means the standards of the quality attributes like assay, measure of content in the formulation, Colour standard, written visual description, identification, and purity etc.

When a product or a material falls out of the lower or upper limit, meaning the observed values, observation is not within the specified limit provided in specification, the product or material quality attributes are not meeting with the specification, it means that they are failing.

The other term for test results which are failing, and not passing through the specification limit, such failing result or observation is called as “out of specification”.

An out of speciation or OOS means the product is failing in to its test and specifications.

There are two possibilities that the product is really failing due to its poor quality, due to its material or faulty manufacturing procedures, act or its failing due to improper testing in the laboratory, analyst’s error, or improper sampling.

Failing product is a risk to pharma companies as it raises questions on its capabilities, and in event the OOS is observed in case of a batch already distributed for sale, then it is a direct risk to the patient’s life.

Out-of -specification results are required to be investigated and the root cause for OOS should be rectified, corrected and preventive action should have been implemented in the CAPA system by logging CAPA number in the CAPA log book. So that the laboratory error does not lead to OOS in future due to the same cause.

Why to investigate the OOS?

Investigation of OOS has a definite and exhaustive procedure where one is required to verify the, weighing of product, or material taken for analysis, accuracy of the weighing balances, proper transfer of the product or material in the test sample preparation, procedure of analysis is verified if it is followed, like sonication time, solubilisation time, filtration method etc., which are tricky, and are skills of analyst.

These are verified in the laboratory by a senior analyst and confirmed if there are any errors in the analysis.

If there is error in a particular step this is corrected through the process of training.

If there is no error in the analysis, further the investigation is done for raw material purity, dispensing, and manufacturing. And a correct root cause is required to be identified through the process of why why analysis, ishikawa fish bone analysis, or brainstorming sessions. After an investigation is completed a root cause is assigned which is logged in to CAPA for correction and prevention in future.

If this is not done there are chances that product or material may face OOS results frequently due to unaddressed causes, in first OOS.

How to handle an OOS?

Every OOS must be investigated as the results found are not confirming to the specifications which are must to comply.

OOS investigation is done in three phases.

Phase 1 investigation of OOS: It is done in the laboratory to verify the error in laboratory testing and analyst’s error.

 

Phase II investigation of OOS: In the event that it is confirmed that there is no error or root cause in phase I, phase two investigation is started focused on the dispensing and manufacturing process and storage etc.

Phase III Investigation of OOS. In event the phase two investigation does not yield any result, Phase Three investigation is started. Which again is focused on the manufacturing process, and resampling and retesting of the product is authorized by QA in phase three investigation.

In all of the above three phases of investigation, a written protocol approved by quality assurance is followed, and every head of the protocol is required to be followed meticulously, without any bias.

Compressed air gas for pharmaceutical use

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Compressed air gas for pharmaceutical manufacturing it’s limit for microbial count. for sterile product the Total Viable Bacterial count should be lesser or equal to 1 cfu/ cubic metre,  and Total fungal count should be nil or not detected, the particle count of compressed air should equal to the at rest condition of the respective clean room, the one colony identified, the bacteria present there should be identified and ensured that it is not pathogenic.

Sampling of Compressed air Pharmaceutical for microbiological assessment.

Due to pressure of compressed gas actual viable microorganisms may not get sampled during sampling of the gas, therefore the pressure is reduced to normal pressure and gas is flown over agar plate through an opening like a slit.

During manufacturing of pharmaceuticals compressed gas is required for operation of machines valves and many things, sometimes compressed gas like nitrogen gas is used for overlaying product surfaces, like in case of injections and sterile dosage form sterile powder for injection, and in liquid dosage form for overlaying the liquid oral product that otherwise may get exposed to environmental oxygen and degrade faster, there nitrogen gas is overlaid , therefore it is required to be free from extraneous matter like.

1)Particles.

2) Endotoxins, pyrogen free. Where gas is going to be part of a sterile drug product.

3)Bacterial and fungal contamination

4) Moisture.

Purity of Nitrogen gas required is more than 99%. It should be oil free

There should not be more than 1% to 1.5 % other gases in the gases used for pharmaceutical use.

Before direct contact of compressed gas with pharmaceutical products, it is filtered through a 0.2 micron air filter and dehumidifier, which removes the entrapped humidity during compression of the gas. There are more fine filters of size 0.1 micron are available one can additionally use such filters to have added assurance.

Nitrogen gas is in the form of compressed gas during compression of gas water molecule get into the gas and are compressed along with gas, and when they leave the port sudden expansion and cooling caused by gas render the water condense over the surface of the nozzle it is a risk of contaminant grow in the condensate which when enter in to a sterile dosage form can pose a serious risk to product. Therefore, before using the compressed nitrogen gas for the overlaying as an inert environment in sterile dosage form.

Also the moisture in the gas can contaminate the clean room specially of class 100 or Class A where the sterile drug product is filled into sterile containers.

How to evaluate microbial load in the. As per the US FDA guidelines 2004 FDA Aseptic Filling Guidance document the particle count of the inert gas should be lesser than or equal to the area in to which it will be used, that means it should not contaminate the product with its over loaded particles, here the particle count should be considered for at rest condition of the manufacturing area where the gas will be used. Compressed Gas for pharmaceutical use should be produced in the same environment as that of a clean room where it will be used in the product.

Reference: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=111.2

Hold time study in pharmaceutical manufacturing

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Hold time study in pharmaceutical manufacturing.

What is hold time study?

Good manufacturing guidelines for pharmaceutical manufacturing mentions that a pharmaceutical manufacturing unit must follow time limitations for stages of manufacturing. US FDA guidelines have not provided a particular time as standard for hold time.

Definition of hold time:

It is a time period for which a particular batch of product or its intermediate or the dispensed raw material can be held at the particular stage without affecting the quality of product, without affecting the stability and purity and quality of the final product.

It is the time of storage of the raw material or bulk product until the start of processing for the next stage, here the next stage for dispensed martial will be manufacturing, and for bulk it will be filling and packing.

Why is the hold time study conducted for the pharmaceutical manufacturing process?

During the hold time process the samples of the product are drawn from the hold containers and testing for the content assay and purity is done, along with microbiological load of the product is also evaluated. And until which time these testing results are found within the acceptable limits that period is assigned as the hold time for the particular stage.

During the study it is observed that the product can be held in the given storage condition in given storage vessels without affecting the quality of product.

Some products assay and other parameters do not support holding for longer time such products will be the outcome of the hold time study, which will set alarm for lower time for holding the product.

How to do hold time study?

A protocol is prepared by quality assurance for conducting hold time study, for dispensed material hold time, bulk product hold time in manufacturing vessels, and bulk product hold time in storage vessels.

The storage vessels which will be used for holding the product are mentioned with its equipment ID and capacity, status of cleanness, etc.

How to store the bulk product, at what storage conditions of temperature and humidity are provided in protocol for hold time study. Also the intermittent sampling frequency and method of sampling of bulk for testing is also provided. After the testing is completed, evaluation for best fit hold time is arrived, based on risk assessment and availability of storage vessels.

A time period by which a product can be held at particular stages is defined as hold time for the particular product for a particular stage, this becomes added assurance for the product in event there is any situation that product is required to be held for any issues, or during vacations. This serves the purpose of addressing the good manufacturing guidelines for pharmaceutical manufacturing.

Hold time for equipment:

During cleaning validation hold time for cleaned and uncleaned equipment is done,

Here are the details provided for hold time for equipment, why it is done and how to do it.

Source: https://www.who.int/publications/m/item/trs992-annex4

Hold time study in cleaning validation

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Hold time study for clean and unclean equipments must be carried out during cleaning validation. It’s one of important aspect that many pharma companies forget to do Hold time study for clean and unclean equipments during Cleaning Validation.

What is Clean equipment hold time dirty equipment hold time ?

During validation of cleaning procedures, hold time study of dirty equipment and clean equipment is studied.

Clean equipment hold time is the time period for which the cleaned equipment after cleaning is stored as per the SOP instructions, and it is the best time period by which the cleanness of the cleaned equipment is maintained, both microbiological count and status of cleanness due to storage.

A cleaned equipment is required to be covered with a clean polyethylene bag and sealed, and during its storage for intermittent period cleanness and microbial count over the surface of cleaned equipment is studied.

It is the time by which there is a visual deposition of dirt or the increase in the bacterial and fungal count over the cleaned equipment when done with swab testing goes up, at that period just before that equipment should be taken for re-cleaning, this period for safety can be curtailed to the previous microbial sample which are complying and visual inspection too is complying.

In the pharmaceutical industry a time period of 7 days to 14 days for cleaned equipment depending on the size of the equipment and storage condition is assigned.

Unclean equipment hold time:

In case of unclean equipment, it is observed that by holding the uncleaned equipment for a particular period. 1) The dirt doesn’t firmly fix on the surface after drying and makes it difficult for cleaning 2) It does not contaminate the other product by virtue of its storage which may hamper the movement of the equipment storage space required for other products. Manufacturer has to decide on this as this may result in a source of cross contamination, therefore a dirty equipment hold time normally is decided to 3 days and maximum up to 7 days.

All the problems with dirty equipment on hold should be verified and corrected during the validation of the cleaning process then the entire process becomes practicable and easy to follow.

Reference: https://www.fda.gov/drugs/guidances-drugs/questions-and-answers-current-good-manufacturing-practice-regulations-production-and-process#1

Cleaning Validation In Pharma

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Cleaning Validation In Pharma

Cleaning validation in pharma manufacturing.

When you thinking of doing cleaning validation of an equipment or a procedure adapted for cleaning, first question you should ask is that is the cleaning validation planed in the validation master plan? If not it’s not late to do that.

Along with cleaning validation most important work needs to be done is dirty equipment hold time study as well as clean equipment hold time study should be done.

Many pharma company don’t do hold time study for dirty equipment and cleaned equipment, this is not proper approach, during cleaning validation itself, hold time study for dirty equipment and cleaned equipment should be done.

Cleaning validation in pharma industry can be defined as “process of establishing through documentary evidence that the cleaning method adapted is capable of maintaining the cleanliness of the equipment so as to prevent the cross contamination from earlier product manufactured in the equipment and to comply with the Good manufacturing guidelines used by regulatory agencies life US FDA, WHO, CDISCO, UKMHRA. TGA, ETC.

It is a mandatory part and responsibility of pharma manufacturing facilities to adapt methods for cleaning during regular production runs, with these adapted cleaning methods it should be assured that no cross contamination of a product occurs in other products.

Good manufacturing practices guidelines have not mentioned any limit for cleanness and traces levels for cleaning agent and previous product. Which means that after cleaning there should not be any traces of a product remaining in the equipment. Neither should there be any microbial load which will be a risk of contamination of product with microbial contamination.

As per GMP guidelines, the minimum carries over limit is not given.

LOD 50 and not more than 0.1% of the daily dose of a drug fundamentals are not required by Food and Drugs administration, rather it is manufacturers data for establishing the safety of the product being manufactured with the adapted cleaning methodology.

Cleaning Validation In Pharma
Cleaning Validation In Pharma

Therefore, a cleaning validation process is run through exhaustive five levels which is also called a life cycle approach towards cleaning validation.

1) Design a cleaning procedure.

2) Test the developed procedure for its workability.

3) Validate the cleaning procedure on the three consecutive batches.

4) Monitor the contaminant residue after every cleaning and evaluate the cleaning procedure.

5) If any improvisation is required, do it at an appropriate stage through a change management system.

Above is a simple explanation of the lifecycle approach for conducting cleaning validation.

Following questions should be answered to know the technical aspects of cleaning validation in the pharma industry.

1) Design a cleaning procedure.

Q: Why design a cleaning procedure?

A: There are many products with different behaviour during cleaning, some products traces don’t get removed easily they require special treatment with base or acid, therefore a detergent or cleaning agent it self when included with such acid or bases work better. This when combined with a robust cleaning process procedure it yields satisfactory results consistently.

2) Test the developed procedure for its workability.

Q: Why to test the workability of cleaning procedure?

A: It’s required for Analytical Method Validation for traces and cleaning agents identification.

3) Validate the cleaning procedure on the three consecutive batches.

Q: Why to use three consecutive batches for cleaning validation?

A: Always first batch falls short for one or the other thing, time required for first batch is always greater than subsequent batch. Second batch is done with all learnings and experiences from first batch.

Third batch then confirms that the results obtained from second batch during validation are similar to third batch. Thus repeatability is confirmed.

4) Monitor the contaminant residue after every cleaning and evaluate the cleaning procedure.

Q:Why Monitor the residue levels after doing cleaning in routine batches?

A:It’s requirements of monitoring products validation cleaning validation through out it’s life cycle.

5) If any improvisation is required, do it at an appropriate stage through a change management system.

Q:Why to do changes in validated procedure?

A:To incorporate the best procedure and learnings from ongoing process and as part of improvisation.

When we try to answer these questions we get the perfect answers for what is at the heart of the requirement of cleaning validation in the pharma industry.

Minimum Allowable carry over limit of previous product: MACO.

The presence of previous product in the traces after cleaning is basically not expected rather it is not allowed as per the good manufacturing practices guidelines. At the same time cleanness is required to be verified for microbial load on the equipment. In MACO the A stands for allowable, it doesn’t mean it is allowed. It is allowed after consideration of risk assessment and establishment of the safety and purity of the product manufactured after adapting the said cleaning procedure.

What is NOEL: NOEL is a concentration of previous products active pharmaceutical products concentration which when included in the next product even after cleaning will not produce any lethal effect on the health of individual, in other words it the limit of concentration beyond which the concentration of previous drug products AIPs if included in next product will be toxic.

NOEL = (LD50 X BODY Weight)/2000 where 2000 is a constant derived from toxicology chronic exposure study.

Minimum carry over limit is calculated based on three criteria’s,

1) Health-based exposure limit (HBEL) 2) therapeutic dose, toxicological, 3) 10-ppm approaches 4) NOEL

1)MACO by health based exposure limit = HBEL \ MBS x MDD

2)MACO by NOEL = (NOELX Batch size in milligram)/ (Daily dose of the productx1000)

3) MACO BY THERAPEUTIC DOSE = Smallest dose of the earlier product x Batch size of earlier product Safety factor/ Largest daily dose of next product.

Microbial load limit for cleaning validation

During cleaning validation, the present microbial load even if it is with in the limit, the microorganism must be separated.and indented, that is which bacteria or fungus is there in the load, if more types of colonies are present those too must be separated and microorganism must be identified, this will help during making decision for disinfection process and decontamination of the manufacturing area, for sterile drug products.

10 PPM criteria for visible residues after cleaning:

Most of the molecules do not exert any untoward effect in such concentration as 10 ppm of previous products active ingredient, most of the APIs are considered safer.

Why is the LD 50 Value of product considered during cleaning validation?

LD 50 Value is a measure of toxicity if a pharmaceutical product having lower LD 50 is considered as most risky, and taken for evaluation in cleaning validation. If these products are cleaned with an adapted cleaning procedure, it is considered safe for other products with higher LD50 than the lowest one taken for cleaning validation study.

Q: Why is a product with API with lowest solubility in water preferred for cleaning validation study?
A: Cleaning is done with water and soap or any approved cleaning agent, therefore the drug molecule which is not soluble in water will not get removed from surface of equipment and may contaminate other product, therefore a cleaning procedure that can remove lowest soluble or water insoluble drug molecule from surface of equipment will also be able to clean other drug molecules which may be soluble in water.

Q: What is the criteria for compliance for visible cleanness in cleaning validation?

A: After cleaning there should not be any visible uncleaned surface or surface with dirt.

Q: What is the method for assessing cleaning of equipment that is not visible directly, how to do assessment of the cleaning of that part of equipment?

A: In such events where swab test or visual observation is not possible, surfaces which are not accessible are rinsed with purified filtered water and examined visually and analytically for traces of previous product or residues of cleaning agent.

Source: https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/inspection-guides/validation-cleaning-processes-793

New Tuberculosis Vaccine developed that does not require to store at cool storage

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New Tuberculosis Vaccine which is a subunit vaccine for TB developed that does not require to store at cool cold storage found the problems with live attenuated TB vaccine can be eliminated with this new vaccine.

New Tuberculosis Vaccine
Tuberculosis Bacteria live in attenuated vaccine

Tuberculosis vaccine consist of live bacteria, mycobacterium bovis, its virulence is reduced by the process of attenuation, vaccine is known to protect all forms of tuberculosis, but the vaccine itself has some serious drawbacks in some patients, because it is a live bacterial vaccine, when injected in to body it forms abbess, therefore it is required to be given in arm in over strong muscle called as deltoid muscle in shoulder.

Sometimes BCG vaccine can’t be given to people who are having positive or reactive tuberculin tests, and also some people with defective pathways for interleukin 12. And patients with suppressed immunity.

If BCG vaccine is injected in soft tissue, then it has a risk of spreading the bacteria to other parts of the body and there is risk of other organs getting damaged due to this.

While BCG vaccine is one of the best options for getting protection against TB and leprosy (up to 80%) BCG vaccine is also effective to some extent against leprosy since the leprosy bacteria is of the same genera mycobacterium. BCG vaccine is sensitive to temperature and it is always required to be stored in a cool place. Since it is a live bacterial vaccine it can’t be stored in deep cool freezers, in cold conditions.

To overcome these problems of BCG vaccine and to protect individuals with suppressed immunity, an alternative for vaccination against TB. Dr. Christopher B. Fox, Ph.D., and scientists at the Access to Advanced Health Institute (formerly the Infectious Disease Research Institute) in Seattle have developed a subunit vaccine which is developed by genetic recombinant technology, cgenetic recombinant technology, of four proteins of Mycobacterium tuberculosis.vaccine is a thermostable vaccine. In a clinical trial 23 individuals were given the thermostable TB vaccine, and found that the new thermostable vaccine (ID93+GLA-SE) imparted strong T-cell responses and yielded more antibodies in the blood compared with people who received conventional BCG vaccine. Daniel F. Hoft, M.D., Ph.D., director of the Saint Louis University Center for Vaccine Development, led the single-site trial at the university’s School of Medicine.

This vaccine (ID93+GLA-SE) is stable against the higher temperature, can be stored at room temperature and the phase one trial of the vaccine has yielded favorable results.

Recall Classification Mock Recall

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Recall Classification Mock Recall detail information.

Q: Why are Pharmaceutical Product is Recalled by pharmaceutical manufacturing companies?

Q: What is the Mock recall? How mush is Time limit set by FDA for recall?
Classification of Recall in pharmaceutical. Give procedure for doing mock recall.

Q: What is type1, 2,3 recall or What is Class A,B,C recall?

This article provides detail information and answers about recall classification mock recall in pharma and all above questions. It is always not that a medicine manufactured by a pharmaceutical manufacturing always meet the standard, or sometimes agencies like Food and drugs administration implement regulations to ban certain medicines time to time as per the recommendations and clinical trial outcomes are not favorable, sometimes pharmacovigilance reports that is drug adverse reactions are reported on a particular medicine, therefore companies take voluntarily, or due to regulatory actions, due to drugs not meeting standards in stability studies, degradation is observed , in such events medicines or drug, pharmaceuticals distributed by a company are withdrawn from sale and called back to pharmaceutical manufacturing company this event is called as recall. Recalls are basically classified as
1) Voluntary recall: recall initiated by a pharmaceutical company due to its own vigilance procedure or market complaint investigation.
2) Statutory recall: Enforced by Food and Drugs administration, Handling market complaint Product Recalls due to legal action, cancellation of license, unapproved product etc.
The procedures and timelines for recalling are very important, since not recalling a medicine that has adverse reactions reported, or class 1 type of recalled drug, will impact on the patient’s life.
Therefore, a pharmaceutical company has to have a very strong system, procedure for doing recalls of drugs products, in event any regulatory agency like Food and Drugs administration asks to do so or in event of a drugs fail in a stability test, or in event a drug reaction is reported, so as to protect the lives of people from the adverse reactions, and from substandard drugs.
The Food and drugs administration has clearly defined a time line for recalling drug products based on the classification of recall. 24 hours to 72 hours for class 1, or Class A, 10 days for Class 2 or class B, 30 days for class 3 or Class C.
There is a timeline for taking a decision within 24 hours by QA to recall the drug product upon noticing the defect or a communication of a regulatory agency from that the above timeline is required to meet is mandatory. A formal communication is required to be sent with all possible ways of communication for freezing of the available stock and recall of the same.
Recalls are classified as per the severity of the nonconformance of drug products. A drug product in question can be recalled completely, taken off from the market based on the severity.
What is type 1 recall or What is Class A recall?
A product which is not approved by FDA or a banned drug product, a product which has life-threatening adverse reactions reported in pharmacovigilance system, a drug product which has found to be defective while investigation of a market complaint, or while reviewing periodically the controlled samples if an adverse observation is there, then the drug product in question is recalled due to possible risks to patient’s life is classified as Class 1 recall or Class A recall.
Timeline for class 1 or Class A recall: Drug product recall classified must be withdrawn from market within 24 hours required it can be extended on satisfactory review upto 72 hours.
At which level it should be recalled: Class 1 recalled product must be recalled from retailer level and if possible from patient’s level.
A public notice is required to be published advising the general public for recall and not using the drug product which is in class 1 recalled.
Class 2 or Class B recall:
A recall is classified as class B in the event a drug product is found to be having moderate or temporary effect on the health of patients which is not serious, a drug product which is defective but does not pose a serious risk to patients is called back under Class 2 or Class B recall.
Timeline for class 2 recall: Drug products classified under class 2 or Class B recall must be withdrawn from the market within 10 days.
Class 3 OR Class C recall: When a drug product is found to be defective during market complaint investigation or any other mean, but the consumption of product by patient do not pose any risk to patient’s life but the quality of product is required to be maintained a defect of whatever nature is required to be removed from the market is classified as class 3 or class C.
Timeline for class 3 recall: Drug products classified under class 2 or Class B recall must be withdrawn from the market within 30 days.
Batch Recall: is a recall of a product where a particular batch of drug product is affected and other batches don’t have any problems and can be consumed by patients.
Lot Recall: A particular lot of a batch when it is not meeting the requirement or it is suited to recall it, is recalled from the market.
Mock recall, what is a Mock recall?:  Due to mandatory requirements of recall time lines by FDA, the pharmaceutical manufacturing company has to review its systems, mechanisms for recalling a drug product, and check if it meets expectations of complete recalling the distributed product meeting the timelines depending on recall classification, mock recall in pharma is conducted.
Therefore, to validate an existing system or procedure for recalling pharmaceutical products, Standard operating procedure is prepared, and a product manufactured in that company is recalled from all possible levels as per class for which the recall drill is required to perform.
A batch or two are decided for recall, within 24 hours the decision is taken by QA.
QA entered in the recall log book and sign, after which, a communication is sent, by SMS, Phone call, or email, all possible means.
Goods are transported back to manufacturers, quarantined, labeled, and reconciliation is done for the qty. A review is done for the mock recall efficiency, the problems arisen during the mock recalls are noted and corrective and preventive actions are put in place for the problems.
After receipt of the recalled batch, QA initiates investigation as per the procedure for investigation of an incidence. Root cause of a defect identified is identified, a corrective and preventive action is taken over the same. A report on recall is prepared and submitted to the local Food and drugs administration or regulatory agency.

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