Media Fill Validation Protocol

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3514

Media Fill

Media Fill Validation Protocol
Area Cephalosporin dry powder Injection

 

        TABLE OF CONTENTS
Sr. No. Contents Page No.
1.0 Protocol Approval
2.0 Objective
3.0 Scope
4.0 Responsibility
4.1 Responsibility of Engineering Department
4.2 Responsibility of Microbiology Department
4.3 Responsibility of Production Department
4.4 Training
4.5 Execution team
5.0 Prerequisite of Media Fill Validation
6.0 Planned Media Fill Validation
7.0 Methodology of Validation
8.0 Re-Validation Criteria
9.0 Destruction Of Media Filled Vials
10.0 Documentation
11.0 Abbreviation
12.0 Reference
13.0 Revision history

 

1.0 PROTOCOL APPROVAL:

Signing of this approval page of Protocol indicates agreement with the validation approach described in this document. If modification to the qualification approach becomes necessary, an addendum shall be prepared and approved .The protocol cannot be used for execution unless approved by the following authorities.

This protocol of Media Fill has been reviewed and approved by the following persons:

 

FUNCTION NAME DEPARTMENT SIGNATURE DATE
PREPARED BY QUALITY ASSURANCE    
REVIEWED BY PROJECT / ENGINEERING    
REVIEWED BY PRODUCTION    
REVIEWED BY QUALITY

CONTROL

   
APPROVED BY QUALITY ASSURANCE    

 

2.0 Objective:

This protocol is designed to establish sufficent data to ensure that the aspectic vial (powder) filling process is adequate and drug product thus produced remains sterile.

This protocol also provides standard procedure for the validation of aseptic dry powder filling process with a set or enviromental conditions and practices to confirm its acceptability in protecting the product from microbial contamination during revalidation as per schedule.

3.0 Scope : 

This protocol is applicable for mediafill validation to be carried out for aspectic processing using dry powder filling machine in cephalosporin injectable area of pharmaceuticals plant.

4.0 Responsibility:

The following shall be responsible;

Quality Assurance Officer/ Executive – For preparation of protocol and execution

Production Officer/ Executive – To execute the media fill activity

Quality Control – To execute the media fill activity

Projects / Engineering Head – To review the protocol and execution support

Production Head – To review the protocol and execution support

Quality Control Head – To review the protocol and execution support

Quality Assurance Head – For adequacy and final approval

4.1 Responsibility of Engineering:

Engineering department shall be responsible for carrying out repair/ modification (if required) prior to validation plan and during the simulation of interventions.

4.2 Responsibility of Microbiology Department:

· Sterility testing of sterile rubber stoppers, sterile flip off seals, depyrogenated glass vial by standard operating/testing procedure.

· Sterility testing of sterile Soyabean casein digests medium, sterility testing of sterile WFI,sterility testing of media filled vials.

· Analysis of vial and bung for particulate matter

· Observation of media fill vials on first day and  after 7 & 14 days of incubation.

· GPT (Fertility test) of media  filled vials after 14 days of incubation.

· Destruction of media filled vias after evaluation and with due authorization of QA Head.

· To carry out investigation incase of the media fill validation failed.

· Identification of the organism upto genus level preferably to species level if gowth is observed in any vial.

· Recording of observation of all test result.

· Preparation of summary report.

4.3 Responsibility of Production

· Providing the machine when agreed upon with the validation group.

· Providing machine operator and supervisor staff.

· Depyrogenation of empty vial and sterilization of rubber stopper, Flip-off seal, containers,machine parts & garments.

· Providing samples wherever necessary.

· Carrying out the aspetic filling process.

· Checking the damage  vials after filling and sealing ,handover damaged vial for distruction to Microbiologist

· Recording of observation, collection of data and filling of BMR.

· Simulation of interventions as worst case situation.

· Cleaning and sanitization of area and equipment after media fill .

  • Receiving of primary packing material such as vials, seals and rubber Stopper after issuance from stores.

4.4       TRAINING:

The training of the testing plan and acceptance criteria for media fill of aseptic process to the personnel responsible for execution shall be provided before execution and a training format shall be filled in coordination with training department. Attach the photocopy of the same with the qualification report.

4.5      EXECUTION TEAM:

Execution team shall be responsible for the execution of media fill report as per approved protocol. The execution team is comprises of:

Production

Engineering

Quality control (Microbiology)

Quality assurance

 

 

5.0 PREREQUISITE OF MEDIA FILL VALIDATION:

Following needs to be qualified before taking the media fill activity:

5.1       Facility qualification

  • Air handling system
  • Water system
  • Utilities
  • Area Qualification

5.2       Approved batch manufacturing record shall be available.

5.3       Validated sterilization and depyrogenation tunnel

5.4       Validated steam sterilizer cum bung processor

5.5       Validated disinfectants

5.6       Pass box validation

5.7       Validated washing machine.

5.8       Validated filling and sealing machine

5.9       Sterile Compressed air

5.10     Personnel training

5.11     Approved batch manufacturing records

5.12     Sterility test of media shall be passed.

 

6.0 PLANNED MEDIA FILL VALIDATION:

6.1         For initial media fill validation plan:

Sr. No. Media fill Run Vial Size Batch size in number Fill weight of sterile media & WFI /Vial
Media(mg) WFI (ml)
1. 3 – Consecutive Run 7.5  ml Glass Vials 5500 vials in each run 150 mg 5 ml
2. 3 – Consecutive Run 10.0 ml Glass Vials 5500 vials in each run 210 mg 7 ml
3. 3 – Consecutive Run 20.0 ml Glass Vials 5500 vials in each run 420 mg 14 ml
4. 3 – Consecutive Run 30.0 ml Glass Vials 5500 vials in each run 630 mg 21 ml

 

Note: Fill weight ± 2.5% of Sterile SCDM per size of vials and add ± 0.5 ml of sterile water for injection.

6.2       Routine media fill validation plan:

Sr. No. Media fill Run Vial Size Batch size in number Fill weight of sterile media & WFI /Vial
Media(mg) WFI (ml)
5. One run for 24 hours 7.5  ml Glass Vials 16500 vials 150 mg 5 ml
6. One run for 24 hours 10.0 ml Glass Vials 16500 vials 210 mg 7 ml
7. One run for 24 hours 20.0 ml Glass Vials 16500 vials 420 mg 14 ml
8. One run for 24 hours 30.0 ml Glass Vials 16500 vials 630 mg 21 


7.0 METHODOLOGY OF VALIDATION:

7.1       Process description

7.2       Process flow.

7.3       Choice of Sterile Soyabean Casein Digest medium for simulation.

7.4       Sampling, Sterility Testing and Filling of Soyabean Casein Digest Medium.

7.5       Component preparation

7.6       Number of vial to be /filling speed and duration:

7.7       Fill volume suitability test.

7.8       Equipment used

7.9       Personnel involvement during media fill run

7.10     Filling procedure

7.11     Planned interventions during media fill

7.12     Unplanned interventions during media fill

7.13     Fertility testing of the filled vials after 14 days of incubation

7.14     Interpretation of results

7.15     Acceptance criteria

7.16     Failure investigation & corrective action

7.17     Precautions

 

7.1       PROCESS DESCRIPTION:

  • The raw material, primary packing materials, containers, and closures issued from stores to production department. The rubber stoppers and flip-off seal are transferred to the respective processing areas. Vials are transferred to decartoning room for further processing.
  • The sterile SCDM shall be issued from micro department to production department.
  • The non-viable air borne particle counts of the critical area; temperature, relative humidity and differential pressure of the area shall be checked and recorded.
  • The garments used in filling area are cleaned and washed in washing machine, inspected, wrapped and then sterilized in the sterilizer as per the validated sterilization cycle as per loading pattern. After the sterilization is over the sterilized garments are transferred to the garment cubicle, located in change room III.
  • Rubber stoppers are sterilized in the sterilizer as per the validated sterilization cycle as per loading pattern. After the sterilization is over the sterilized rubber stoppers are transferred to filling area should be used for media fill.
  • The vials are decartoned in Decartoning room, inspected through conveyer belt, washed through the vial washing machine and the washed vials are depyrogenated in Sterilization and depyrogenation tunnel.
  • The washed and sterilized machine parts transferred in vial filling and stoppering machine by using mobile LAF. The sterilized and depyrogenated vials get collected & loaded on in feed turntable of the vial-filling machine.
  • The sterilized rubber stoppers are charged into hopper and raw material is transferred into the sterile container is attached to the hopper. WFI is filled in each vial by using media filling assembly.
  • The filled weight is adjusted of each filling station as per the fill weight mentioned in BMR and Weights of vials from all the filling stations and the average weight shall be checked and recorded at regular intervals.
  • Filled and stoppered vials are sealed on vials sealing machine. The sealed vials are then checked on line visually for any defect. Defective vials are collected separately and good vials are allowed to move forward to collect in tray.
  • After completion of the batch raw material and primary packing material are reconciled, batch yield are calculated and recorded in the batch manufacturing record (BMR), Batch analysis reports and other supporting documents shall be attached with BMR.
  • The BMR is sent to the QA for review.
  • The environmental monitoring for viable counts. [i.e. Settling plate, air sampling, surface monitoring (SWAB) nonviable counts and personnel monitoring] are carried as per their  respective SOP’s.
  • The hold time of bung and seal should not be more than 72 Hrs from sterilization to final filling of batches.

7.2       FLOW CHART FOR ASEPTIC PROCESS:

7.3       CHOICE OF STERILE SOYABEAN CASEIN DIGEST MEDIUM FOR SIMULATION

Sterile Soyabean casein digest medium powder is selected for media fill activity because of the following reasons:

  • Low selectivity of media i.e. it supports the growth of wide range of organisms including bacteria and fungi.
  • Good growth promoting property.
  • Flow ability of Sterile Soyabean casein digest medium through hopper and dosing wheel is good.
  • Sterile Soyabean casein digest medium is easily soluble in water for injection.
  • Clarity of the media when dissolved in water for injection to allow to observe the turbidity if present at ease.
  • It does not inhibit the growth of microorganisms.

 

7.4       SAMPLING, STERILITY TESTING AND FILLING OF SOYABEAN CASEIN DIGEST MEDIUM:

Procure sterile dehydrated Soyabean Casein Digest Medium (SCDM). Bring the dehydrate media by sanitizing outer surface of media packet to sterility testing area of microbiology lab. Perform sampling of sterile SCDM as per respective SOP. Perform sterility testing and fertility testing as per respective GTP. After 14 days of incubation the media shall be taken for media fill activity (if sterility complies).

7.5       COMPONENT PREPARATION:

Primary packing material such as rubber bungs, seals, garment, machine parts and other accessories shall be sterilized by Autoclaving as per respective SOP.

These sterilized materials shall be kept under LAF in Cool Zone Area.

7.6       NUMBER OF VIAL TO BE FILLED /FILLING SPEED AND DURATION:

At least 16,500 nos. of vials to be filled for 3 consecutive batches of media fill and each batch will be considered as 5500 vials/batch/shift for 24 Hrs media filling activity for initial media fill validation while one run 16500 nos. of  vials shall be taken for routine media fill validation for 24 hrs filling.

The media filling activity shall be carried out at slow production speed. The duration of media fill run shall be of three shifts.

7.7       FILL VOLUME AND SUITABILITY:

The fill volume of media shall be covered at least 65 to 70 % of vial capacity, the fill weight and volume shall be decided based on solubility of medium. The solubility of sterile Soyabean Casein Digest medium is 30 mg /ml (as per supplier specification).

7.8       EQUIPMENT USED:

Vial washing machine, Steam sterilizer cum bung processor, sterilizing and depyrogeneting tunne, vial filling & sealing machine and blender bin  all equipment shall be qualified at the time of media fill activity.

7.9       PERSONNEL INVOLVEMENT DURING MEDIA FILL RUN

During filling operation maximum seven persons shall be present inside the filling room. All persons involved in routine aseptic operation should be included in any one of the following critical aseptic operations in the run.

  • Unloading of sterilized components from autoclave.
  • Opening of rubber stopper container and charging of stopper into stopper hopper.
  • Handling and transfer of machine parts to vial filling room, assembling of machine parts, setting of machine for powder filling and for liquid media filling.
  • Transfer of containers containing sterile soyabean casein digest medium powder from microbiology department to vial filling room and thereafter charging into product hopper.
  • Handling of sterilized media in the vial filling room for filling into vials.
  • All person involved in routine filling to enter operation shall be involved in media filling operations
  • Microbiologist shall enter into critical area for area monitoring, personnel monitoring and sampling. All microbiologists involved in sampling and environmental monitoring during normal manufacturing periods shall take part in system simulation run over a period of once in a year.
  • The maintenance personnel (qualified to enter into critical area) shall be required to carryout minor machine adjustment and will be monitored for personnel counts

7.10        FILLING PROCEDURE

7.10.1     Obtain the line clearance before starting filling operation of the batch for any leftover raw material, vials and rubber stoppers etc of previous day/batch

7.10.2     Check the area and machine for cleanliness.

7.10.3     Check the temperature, differential pressure and relative humidity of vial filling room.

7.10.4     Take containers of sterile SCDM as per requirement of batch manufacturing record.

7.10.5     Wipe the sterile SCDM container with 70% IPA. Transfer the container in dynamic pass box under UV light contact for 15 minutes before taking the SCDM container in aseptic area.

7.10.6     Transfer the sterile SCDM into blender bin and mix them for 30 minutes for each batch, after that transfer the blended sterile SCDM powder in pre sterilized container used for filling activity.

7.10.7     The above-mentioned activity is performed to simulate the actual condition during routine production

7.10.8     Filter the required WFI through 0.2-micron filter for each batch of media fill and collect the filtrate in presterilized pressure vessel through sterile silicon tube.

7.10.9     Decartoned the required vials for each batch of media fill in Decartoning area. Washing, sterilization and Depyrogenetion of vials shall be performed using sterilizing and depyrogenating tunnel.

7.10.10   Assemble the sterilized machine parts and transfer sterilized rubber stopper, flip off seals, Sterile Soyabean casein digest medium containers in the hopper. Additional attachment shall be installed for filling required amount of sterile water for injection by adjusting the RPM.

7.10.11   Carry out the media filling activity followed by sterile water for injection filling. The fill weight and fill volume shall be ± 2.5% of sterile SCDM and in the same vial fill ± 0.5 ml of sterile WFI.

7.10.12   Verify the weight and volume of sterile SCDM and sterile WFI respectively and note down the reading in BMR.

7.10.13   Carry out the in process testing as mentioned in the BMR, which includes checking of sterile powder of SCDM, volume verification for sterile WFI with SCDM, color and clarity test, leak testing of filled vials.

7.10.13   Microbiologist shall performed environmental monitoring which includes settle plate exposure, active air sampling, personnel monitoring, wall and floor monitoring. Expose the microbiological plates to enumerate anaerobic microorganism as per respective SOP.

7.10.14   Carryout non-viable particle count monitoring before media fill activity.

7.10.15   At least 16,500 nos. of vials to be filled for 3 consecutive batches of media fill and each batch shall be filled for 24 hrs. At the end of one shift filling, bunging and sealing operators shall be replaced. First the operators have to enter in the filling area then the previous operators will come out from the area.

7.10.16   Thorough inspection of vials shall be performed by visual inspectors, Sort out and reject those vials having obvious breach of container / closure integrity (Non integral vials) such as cracked container, broken container, Containers with missing stopper.

7.10.17   The media fill activity shall be performed with frequent interventions, which we come across during routine production to simulate actual condition.

7.10.18   The vials filled during each intervention shall be collected in tray. It shall be marked with name of intervention and code no as per defined in protocol and same shall be recorded in report.

7.10.19   Incubate the vials at 20 – 25°C for seven day and carryout inspection of vials to check any sealing defect and record the observation. After 7 days of incubation observe the vials for any microbial contamination and record the observation. Transfer the vials at 30-35°C for another 7 days. After 7 days of incubation at 30-35°C observe the vials for microbial growth by microbiologist and record the observation.

 

7.10.20 Sampling plan for media fill activity

Sr.

No.

Type Of

Sample

Stage Sample Quantity Test Performed
  1 Sterile WFI From Sterile WFI Filling Nozzle from each container 100 ml  Sterility
  2 Rubber stopper After sterilization Sterilized rubber bung 10 + 5 Particulate matter
BET
  3 Rubber Stoppers From Hopper 20 nos. Sterility  (Initial)
Sterility (Middle)
Sterility (End)
  4 Flip Off Seals After Sterilization From Hopper 20 nos. Sterility  (Initial)
Sterility (Middle)
Sterility (End)
  5 7.5 ml Glass Vial From outlet of vial washing machine 10 Nos. Particulate matter
  6 7.5 ml Glass Vial From Filling m/c Turn table 20 nos. Sterility  (Initial)
Sterility (Middle)
Sterility (End)
  7 7.5 ml Glass Vial From Filling m/c Turn table 10 nos. BET (initial)
BET (middle)
BET (end)
  8 7.5 ml Glass Vial From Filling m/c Turn table 10 nos. Particulate matter
  9 Compressed air Compressed air from pendent 1000 liter Sterility (before filling)
Sterility (after filling)
 10 Compressed air Compressed air from pendent 1000 liter Particulate matter (before filling)
Particulate matter (after filling)
 11 Nitrogen Gas From Nitrogen purging nozzle before & after filling 1000 liter Sterility (before filling)
Sterility (after filling)
 12 Nitrogen Gas From Nitrogen purging nozzle before & after filling 1000 liter Particulate matter (before filling)
Particulate matter (after filling)
 13 Dehydrated media After blending 6 g Sterility
 14 Dehydrated media From at the time of charging into container 6 g Sterility
 15 Dehydrated media From Hopper 6 g Sterility
 16 Filled and sealed vials From Filling 14 vials Growth promotion test & pH (Initial)
Growth promotion test & pH (middle)
Growth promotion test & pH (end)
 17 Filled and sealed vials At Optical visual Inspection 20 vials Sterility  (Initial)
Sterility (Middle)
Sterility (End)
 18 Left Over Media From Filling Hopper 6 g Sterility
 19 Filled media vial After visual inspection 10 vials Positive control
 20 Post GPT sample After 14 days incubation 14 vials GPT

 

7.11     PLANNED INTERVENTIONS DURING MEDIA FILL

Sr. No. Interventions Rational Frequency Code
1. Sampling of sterile WFI from pressure vessel WFI must be sterile, to be used in media fill activity Two time 1.
2. Sampling of sterile SCDM from the Hopper Sampling from the container is done in normal course. Three time 2.
3. Removing of fallen vials from the turntable with forceps This is normal activity which occurs during routine production Five time 3.
4. Charging of sterile powder in hopper. This is normal activity which occurs during routine production Three times 4.
5. Charging of Rubber stoppers in hopper. This is normal activity which occurs during routine production Five times 5.
6. Removing vials for weight variation This is normal activity which occurs during routine production Nine times 6.
7. Adjustments of fill weight This is normal activity which occurs during routine production Four times 7.
8. Setting of compressed air & vacuum supply to dosing disc. This is normal activity which occurs during routine production  

One time

8.
9. Collection of loosely fitted plugged vials with forceps Deliberately creation of un favorable condition One time 9.
10. Stoppage of filling machine. This is normal activity which occurs during routine production Three  times 10.
11. Failure of power supply for three minute. This is not happened during normal production it is taken as worst-case scenario  

Two

times

11.
12. Removal of chocked piston. To demonstrate the ability of operator to correct the problem without contamination  

 

One time

12.
13. Change of operator This is normal activity which occurs during routine production One times 13.
14. Tools assembly centering by Engineer To demonstrate the ability of engineer to correct the problem without contamination. One time 14.
15. Checking of electrical panel by Engineer To demonstrate the ability of engineer to correct the problem without contamination One time 15.
16. Adjust the filling speed of machine at optimum This is normal activity which occurs during routine production One time 16.
17. Cleaning of spilled powder, This is normal activity which occurs during routine production One time 17.
18. Adjustment of bung pressure roller This is normal activity which occurs during routine production One time 18.
19. Pushing vials in channels by forceps This is normal activity which occurs during routine production Five times 19.
20. Running the machine at higher speed This is normal activity which occurs during routine production One time 20.
21. Running the machine at Low vacuum. This is normal activity which occurs during routine production One time 21.
22. Running the machine at High vacuum. This is normal activity which occurs during routine production One time 22.
23. Adjustment of stopper This is normal activity which occurs during routine production One time 23.
24. Vials collected with only WFI filling to check volume variation Deliberately creation of un favorable condition One time 24.
25. Production person entry into filling area This is normal activity which occurs during routine production One time 25.
26. QA person entry in filling area This is normal activity which occurs during routine production One time 26.
27. Filling operation with open side guards. Deliberately creation of unfavorable condition One time 27.
28. Switch off LAF and AHU will switch ON for 2 minutes. Deliberately creation of unfavorable condition One time 28.
29. Switch off AHU and LAF will switch ON for 2 minutes. Deliberately creation of unfavorable condition One time 29.
30. Charging of Seal This is normal activity which occurs during routine production Ten time 30.
31. Sampling of Vials from turntable This is normal activity which occurs during routine production Three time 31.
32. Sampling of Rubber stopper from hopper This is normal activity which occurs during routine production Three time 32.
33. Sampling of Seals from Hopper This is normal activity which occurs during routine production Three Time 33.

 

7.12     UNPLANNED INTERVENTIONS DURING MEDIA FILL

All unplanned interventions/breakdown e.g. Blockage of rubber stopper chute / flip-off chute and its clearance, vial upright on turntable and in feed track by using forceps shall be immediately reported to Head QA and same shall be documented in media fill validation report.

7.13     FERTILITY TESTING OF THE FILLED VIALS AFTER 14 DAYS OF INCUBATION

The objective of this test is to observe that the media in the filled vial remains growth-promoting up to the end of incubation period.

7.13.1 Procedure for preparation of negative and positive control for comparison of media filled vials:

  • Media filled vials shall be checked against negative and positive control vials used as reference.
  • Microbiologist shall prepare negative and positive control separately in microbiology testing area. The required quantities of media are taken aseptically in sterilized conical flask and add required quantity of sterile water for injection and dissolve completely. Pour aseptically in depyrogenated vials. The prepared vials shall be incubated at 20 to 25°C for 7 days and 30 to 35°C for next 7 days. If no any growth observed, the vials shall be considered as negative control for checking media filled vials. Negative control shall prepare before 2 weeks of media fill activity.
  • During media fill validation the positive control shall be prepared. Prepare the vials containing sterile media is as per procedure mentioned in the negative control procedure. Add 10-100 CFU culture of different organism in the vials and incubate the vials at respective temperature to get luxuriant growth. These vials shall be used as positive control for media fill vials. The positive control vials shall be used within 15 days after incubation.
  • The positive and negative control vials shall be prepared for each vial size and kept in microbiology lab and shall be used during visual inspection of Media filled vials as a reference.

7.14     INTERPRETATION OF RESULTS

Observe the growth/turbidity in media filled vials, after the 7 and 14 days of incubation; first incubate media filled vials at 20ºC to 25ºC for 7 days. After completion 7 days incubation period visual checking shall be done for contamination of filled vials.

Another 7 days Incubation shall be carried out at 30ºC to 35ºC, at the end of incubation period; visual checking shall be done for the contamination of filled vials. Note down the temperature throughout incubation period and record.

7.15     ACCEPTANCE CRITERIA

  • Sterile Soyabean casein digest medium filling operation must stretch over a full operation shift with a maximum of 24 hours duration for three shifts.
  • Environment and personnel monitoring during the course of Sterile Soyabean casein digest medium fill Operation shall be carried out.
  • The filling operation at the minimum speed at low vacuum, high vacuum of the Filling Machine shall be carried out.
  • One contaminated vial should result in an investigation, including consideration of repeat media fill.
  • Two contaminated vials considered cause for revalidation, further investigation contaminated microorganisms should be identified to genus/species level to determine the possible source of contamination

7.16     FAILURE INVESTIGATION & CORRECTIVE ACTION

In case of failure of media fill validation following investigation shall be carried out.

  • For any run size, intermittent incidents of microbial contamination may be indicative of low-level contamination that shall be investigated. Investigation of gross failures should include the potential impact on the sterility assurance of batches manufactured since the last successful media fill.
  • The interval between the washing and drying and the sterilization of components, containers and equipment as well as between their sterilization and use should be minimized and subject to a time-limit appropriate to the storage conditions.
  • Handling Components, containers and equipment after the final cleaning process in such a way that they are not re contaminated.
  • Environmental monitoring shall be investigated which was carried out during media fill validation.
  • If system simulation run fails failure investigation shall be carried out as per respective SOP.

7.17     PRECAUTIONS

Check the absence of Sterile Soyabean casein digest medium in the filling area after completion of media fill run. Clean the entire area with disinfectant as per used in routine schedule & perform fogging after cleaning.

8.0       Re-Validation Criteria:

Media filling should be revalidated under following conditions:

  • Any major changes in facility or in Filling line machine.
  • Any modification of sterilization parameters
  • After any major maintenance or major breakdown in vial filling machine or in HVAC system.
  • Periodic revalidation shall be carried out at least 1run in every 6 months. It will be completed within 15 days from the due date.

9.0       DESTRUCTION OF MEDIA FILLED VIALS:

  • After completion of 14 days incubation of media filled and sealed vials, Destruction of media filled vials shall be done by opening vials and media shall be poured in container, having 5 % Savlon solution. The vial shall be kept in another container having 5 % savlon solution.
  • Rubber stoppers and seals shall be kept in container having 5% savlon solution.
  • Leave it for one hour, then discard the media in drain and vials shall be sent to scrap yard for destruction by crushing.

10.0     DOCUMENTATION

  • Approved validation protocol.
  • Executed Batch Manufacturing Record for system simulation test
  • Separate report shall be prepared for each size of vials.

11.0     ABBREVIATION

CFU                :           Colony Forming Unit

SDT                 :           Sterilization and depyrogenation tunnel

PVT                 :           Private

QA                   :           Quality Assurance

RODAC          :           Replicate Organism Detecting and Counting

SOP                :           Standard Operating Procedure

LAF                 :           Laminar Air flow

SCDM             :           Soyabean Casein Digest Medium

FTGM             :           Fluid Thioglycollate Medium

GPT                :           Growth Promotion Test

BET                 :           Bacterial Endotoxin Test

MLT                 :           Microbial Limit Test

12.0     REFERENCE:

EU Guidelines: Annex-I, Manufacture of Sterile Medicinal Products.

WHO TRS 961: Annex – 6, WHO good manufacturing practices for sterile pharmaceutical products

In house: SOP’s.

13.0     REVISION HISTORY

Sr. No Protocol no. Detail of Revisions
01 Protocol revised due to addition of routine media fill plan.
02 Protocol revised due to updating of sampling   plan.

 

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