MAXIMUM NO.OF REJECTED VIALS ACCEPTABLE AT 95% CONFIDENCE LEVEL
PERCENTAGE OF FAILURE
| || || |
| || || || |
| || || || |
| || || || || |
* Normal media fill run size
Aseptic Process validation--Media Fill operation in the sterile dry powder filling
1.0 OBJECTIVE: To lay down a procedure for Media Fill operation in the sterile dry powder Filling facility..
Microbiologist, Operator concerned/Production officer/QA Officer
Quality Control Manager/ Production Manager
4.0 Ensure that all the equipments, HVAC system, water system and other utility services of the facility are validated.
4.1 Ensure that the Gamma irradiation certification report of the lactose + SCDM (Soyabean Casein Digest) mixture (3:1) from BARC and sterility test report (done in-house) is available.
4.2 Ensure that solubility test report and growth promotion/inhibition test report of sterile
lactose+SCDM mixture is available. [Solubility should be NLT 1gm/10 ml of WFI].
4.3 Ensure that solubility test report and growth promotion/inhibition test report of sterile lactose+SCDM mixture is available. [Solubility should be NLT 1gm/10 ml of WFI].
4.4 Ensure that freshly distilled WFI to be used for filling, is autoclaved and the sample given for sterility test.
4.5 Ensure that all the contact parts of Dry Powder Filling machine are duly cleaned and sterilized or sanitized.
4.6 Ensure that the last Environmental Control Reports of the area are conforming to the acceptance standard.
4.7 Ensure that the Liquid Filling machine is done inside the sterile filling area on the previous day after autoclaving /sanitization.
4.8 Ensure by manometer readings, that the pressure balancing of the sterile area is as per requirement.
4.9 Ensure that the cleaning, sanitization and fumigation of the area is done on the previous day.
4.9 Enter the sterile area as per SOP using gowns sterilized 4days back.
4.10 Check the cleanliness of the sterile area.
4.11 Check the cleanliness of the Liquid Filling machine.
4.12 Check and confirm the temperature and RH of liquid filling room is as per the requirement.
4.13 Assemble the Liquid Filling machine.Ensure that that filling of liquid and liquid can be done
4.14 Measure the nonviable particulate count of filling cabinet and filling room.
4.15 Bring the autoclaved WFI container near the liquid filling assembly.
4.16 Transfer sterile SCDM liquid from the container in to liquid hopper.
4.17 Transfer sterile dried rubber stoppers (sterilized 4 days back) in to the hopper of stoppering unit. Send sample for sterility testing simultaneously.
4.18 Put the inlet suction tube of Liquid Filling Assembly into the WFI container.
4.19 Set the Liquid Filling machine for the respective dose.
4.20 Remove the Liquid Filling Assembly and all the contact parts. Disinfect it, clean it and get it sterilized/sanitised.
4.21 Ensure that all the left over rubber stoppers are given outside the sterile area for destruction.
4.22 Shut down the vial liquid-filling machine as per SOP
4.23 Ensure that all the tools and accessories containers etc. used during media fill are given for cleaning/sanitization/sterilization.
4.24 Follow the cleaning and sanitization SOP for cleaning of sterile area.
4.25 Do the extra cleaning and sanitization of the floor/walls/machine after media fillrun with 10% Bacillocide and Lysol solution
4.26 Initial validation: During initial validation, it should qualify all three consecutive media fill run i.e. during each run there should not be growth in more than two vials.
4.27 Revalidation: Only one media fill run in which there should not be any growth in more than two vials.
ELIGIBILITY CRITERIA FOR PERSONNEL PERFORMING MEDIA FILL RUN :
4.28 Persons involved in media fill should be medically examined and declared fit within last one year.
4.29 Persons should be trained on general hygiene and current gowning procedure, and the present health condition should be O.K.
4.30 The personnel should be microbiologically monitored during run.
In case of any positive growth in any vial during the incubation period.\
4.31 It should be isolated and identified to the genus level.
4.32 If the isolated organism is other than the house flora, thorough investigation shall be carried out by Quality Assurance and Production.
4.33 The source of the contamination must be established.
In case of any failure in media fill run:
4.34 When there is no assignable cause, media fill shall be repeated three times and production should commence only after all the three runs meet the acceptance criteria.
4.35 When there is assignable cause, after rectification of the cause, repeat the media fill run once.
4.36 Before and during media fill run no special cleaning shall be carried out.
4.37 Normal production can resume only after minimum one day of environmental monitoring compliance report.
4.38 Batches filled before the final result of the media fill run shall not be released to the market till the media fill run passes in case of initial validation.
4.39 The routine environmental monitoring plates shall be kept for 14 days (in case of any growth) to help in investigation of any positive growth in the media filled vials.
4.40 If for any reason the media fill run is considered invalid vials shall not be incubated.
4.41 Media fill runs can be aborted for the same reason that a product lot would be aborted. All media filled units filled before an incident that would cause an aborted fill must be incubated.
4.42 During media fill all the Operators, Officers& Maintenance staff who are authorized to do the sterile filling, supervision and maintenance must be involved in media fill trial.
4.43 The volume of liquid filled must be sufficient to wet all surfaces including the closure and to facilitate inspection.
4.44 The line must be run at a slower speed than normal production run to give greater exposure time.
4.45 Total duration of the routine media fill must be the same or more as the longest process conducted on that line.
4.45 The incubation temperature of the filled containers must be sufficient to promote microbial growth at 30-35oC. for 336hrs(stored upright) followed by 20-25oC. for 336 hrs. (stored upside down).
4.47 Personnel that conduct the inspection of incubated media fills must have training on basic microbiological concepts ,concepts of media fill and examples of contaminated container showing various stages of growth.
POST MEDIA FILL RUN :
4.48 Filled incubated vials should be optically checked by microbiologist and certified.
4.49 Incubate the vial samples with no growth approximate 5 vials for 14 days with normal house flora and 5 vials with organisms used for the sterility test growth promotion for 14 days.
4.5 Temp. range for incubation 1st two week at30 to 35o C. (vials stored upright).
4.51 Next two week at 20 to 25o C. (vials stored upside down).
4.52 These vials should show promotion of growth.
ANNEXURE - I
LIST OF PERMITTED INTERVENTIONS DURING FILLING
These are the activities which are performed during normal working in the sterile filling area:
1) Adjustment of weight in the dosing wheel.
2) Adjustment of Stopper holding spring.
3) Transfer of liquid from container to hopper.
4) Transfer of stoppers from bag to hopper.
5) Picking unstoppered vials from the outfeed back to conveyor for stoppering.
6) Adjustment of separator.
7) Picking up of fallen vials from turn table.
8) Cleaning of machine with vacuum cleaner.
9) Adjustment of stoppering channel height.
10) Adjustment of stoppering pressure rollers.
11) Replacing of a piston from the wheel.
12) Adjustment of turn table over load sensor.
13) Lifting and closing of the LAF cabinet door.
14) Checking the weight in balance.
15) Adjustment of dosing air.
16) Cleaning of vacuum pot.
17) Pushing stopper in the channel by forceps.
18) Power interruption (samples should be marked)
19) Number of personnel in sterile filling area (8 persons).
20) Multiple dosing of the liquid.
21) Running the machine at a slower speed than actual production run.
22) Covering the working shift usually 12 hours and shift Change over
23) Entry of maintenance person for repairing of M/C
ANNEXURE - III
ACCEPTANCE CRITERIA FOR MEDIA FILL SIMULATION
Labels: Aseptic Process Validation