1.0 OBJECTIVE
1.1 To define procedures for validating and maintaining the validation of all aseptic filling processes and qualification of the quality of the product by system/facility/equipment.2.0 SCOPE
2.1 This procedure applies to all aseptically filled sterile products intended for human use.
3.0 RESPONSIBILITY
3.1 The Validation personnel coordinate the aseptic filling validation program and write the sterile media aseptic filling processes reports.
3.2 Manufacturing personnel the sterile media aseptic filling processes and performs the sterile media fills.
3.4 QC personnel to perform the testing and assist with the monitoring required for each sterile media fill.
4.0 ACCOUNTABILITY
4.1 Manager QA
5.0 REFERENCE (S)
5.1 In- house.
6.0 PROCEDURE
6.1 EXIT AND ENTRY PROCEDURE
6.1.1 All Operators and Supervisors enter department as per Defined Gowning procedure.
6.2 AMPOULE FILLING MEDIA
6.2.1 The media fill run shall be performed for approximately the same duration as required for filling of a normal production batch (approx. 12 hours).
6.2.2 Batch (Media) manufacturing shall be done in the initial hours of the 1st shifts, followed by other processing steps normally followed.
6.2.3 Nitrogen flushing shall not to be done during media filling.
6.2.4 The filling of media shall be done in the following sequence:-
6.2.4.1 The media (Soybean Casien Digest Madium) batch shall be manufactured in the manufacturing area. The bulk is then aseptically filtered into a sterile holding tank (under LAF) in the sterile area. The tank containing the filtered solution is then connected sterile silicon pipeline and filling done in ampule without employing the use of on-line cartridge filters/filter housing on the machine.
6.2.4.2 Fill volume of media as per the protocol. (The fill volume of media in units need not equal the fill volume of finished product units, the quantity filled shall be sufficient to wet all the inner surfaces of the unit & to enable an inspection to detect positives.)
6.2.4.3 Filling activity is performed in the filling room (especially the filling zone) under LAF.
6.2.4.4 Consecutive first three runs will be validated with sterile media solution.
6.2.4.5 Simulate the adverse condition testing of the system (details of adverse conditions given separately in step 6.4) after filling approximately 10,000 units.
6.2.4.6 Filling to be planned in a manner such that the operator covers the activities during the shift change over.
6.3 VIAL FILLING MEDIA:
6.3.1 The media fill run shall be performed for approximately the same duration as required for filling of a normal production batch (approx. 12 hours).
6.3.2 Batch (media) manufacturing shall be done in the initial hours of the 1st shifts, followed by other processing steps normally followed.
6.3.3 Nitrogen flushing shall not be done during media filling.
6.3.4 The filling of the media to be done in the following sequence-
6.3.4.1 The media (Soybean Casien Digest Madium) batch is manufactured in the manufacturing area. The bulk is then aseptically filtered into a sterile holding tank (under LAF) in the sterile area. The tank containing the filtered solution is then connected with is sterile silicon pipeline and filling done in vials without employing the use of on-line cartridge filters/filter housing on the machine and then dosing of sterile lactose in vials.
6.3.4.2 Transfer the sterile lactose through material airlock into the sterile area and transfer the sterile lactose aseptically into the previously sterilized hopper of the vial filling machine. Three runs will be validated with 250 mg sterile lactose and 5 ml media solution, 500 mg sterile lactose with 5 ml media solution and 1000 mg sterile lactose with 10 ml media solution to validate the weight range from 250 mg to 1000 mg.
6.3.4.3 Fill volume of media or weight of Powder as per the protocol. (The fill volume of media filled units need not equal the fill volume of finished product units, the quantity filled shall be sufficient to wet all the inner surfaces of the unit & to enable an inspection to detect positives.)
6.3.5 Filling activity is performed in the filling room (especially the filling zone) under LAF.
6.3.6 Simulate the adverse condition testing of the system (details of adverse conditions given separately in step 6.4) after filling approximately 10,000 units.
6.3.7 Filling to be planned in a manner such that the operator covers the activities during the shift change over.
6.4 ADVERSE CONDITIONS: (AMPULE/ VIAL)
6.4.1 Filling machine OFF: For 60 minutes (The filtered air supply in the filling zone not to be put off. Imitate maintenance activities that are likely to take place during routine filling process, after restarting approx. 1,000 units to be filled)
6.4.2 LAF Filtration OFF: For 5 minutes (filling to be done when LAF is OFF)
6.4.3 Air Handling Units power OFF: For 5 minutes (ALL the AHU’s of the sterile and the adjoining areas to be switched OFF, filling to be done when AHU’s are OFF).
6.4.4 Total Power OFF for 2 minutes:
(ALL the AHU’s of the sterile and the adjoining areas, filling m/c, LAF’s etc to be switched OFF, after restarting approx. 1,000 units to be filled)
6.4.5 Highest (250 ampule/vial min.) speed of machine:
approx. 1,000 units to be filled
6.4.6 Change in tubing’s: Approx. 1,000 units to be filled
6.4.7 Ampule/Vial Sterilizing tunnel OFF: For 5 minutes (total power supply of the tunnel is to be switched OFF, after restarting tunnel all the units from the cooling zone to be filled).
6.5 STORAGE OF FILLING UNITS (AMPULE/VIAL)
6.5.1 Collect all units in a tray or suitable container, Store in previously maintained temperature defined area or incubator.
6.5.2 First Store at temperature 20 -25 ° C for seven days.
6.5.3 After that Store at temperature 30 -35 ° C for seven days.
6.6 RESULT
1. After the incubation period of the media-filled containers, they are visually examined for microbial growth. Contaminated containers should be examined for evidence of container/closure damage which might compromise the integrity of the packaging system. Damaged containers should not be included as failures (positives) when evaluating results.
2. The number of containers used for media fills should be sufficient to enable a valid evaluation. For small batches, the number of containers for media fills should at least equal the size of the product batch. The target should be zero growth and the following should apply:
• When filling fewer than 5000 units, no contaminated units should be detected.
• When filling 5,000 to 10,000 units,
a) One (1) contaminated unit should result in an investigation, including consideration of a repeat media fill;
b) Two (2) contaminated units are considered cause for revalidation, following an investigation.
• When filling more than 10,000 units:
a) One (1) contaminated unit should result in an investigation;
b) Two (2) contaminated units are considered cause for revalidation, following an investigation.
Abstracted from: PIC 007-5 dated 01 July 2009 Recommendation on the Validation of aseptic processes.
6.7 DESTRUCTION OF MEDIA:
6.7.1 After 14 days media shall be destructed as per sop or procedure.
6.8 FREQUENCY OF MEDIA FILLS (AMPULE/VIAL):
6.8.1 Initial Three consecutive Successful Run(all container size employed for filling on the machine) before start production for qualified area or equipment.
6.8.2 Then after once in 6+1 month of Single run any suitable volume for re-qualification of area or equipment.
6.8.3 If any change or modification of critical equipment or area then goes for single run media for any suitable volume before starting production.
6.8.4 If critical equipment or area is not in use for about one month then go for single run media for any suitable volume before starting production.
6.8.5 As and when required.
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Dear Sir, please tell why a concentration of 3% SCDM is used in media fill?
ReplyDelete3% CDMA is sufficient to support the microbial growth.
ReplyDeleteSir,
DeleteIs it necessary to consider the specific gravity of 3% SCDM during batch manufacturing?
Whw many chances of media fill failure during intervention activities?
DeleteMy company plan to do media fill so i want to know the routine and non routine intervention use during media fill
ReplyDeleteDear sir, please explain why sterile lactose is filled in the vials during medial fill.
ReplyDeleteI have four pack size 20ml,30ml,40ml&100ml what is the frequency for media fill & how to prove that last six month's production was ok if one pack is not revalidated within 6month
ReplyDeleteHow can we observe/Inspection Media Fill in HDPE Plastic 100 mL Bottle ?
ReplyDeleteHi Mohammad, it is strongly recommended that media fill shall be performed in the clear transparent bottles. if this provision is not available, there are different colour medias are in market which when contaminated could change the colour and provides a clear cut visibility.
DeleteHow can I justify production batches (before media fill) if one unit show growth in semi annual media fill.
ReplyDeleteDear sir,
ReplyDeleteWe have different pack size like 1ml, 2 ml, 5 ml & 10 ml sterile ampoule/vial product. In case of re validation of media fill study on semi yearly basis if we would have a risk assessment study along with initial complete validation and worst case consideration study and then if we plan to consider most risky pack size for re validation on semi yearly basis does it complies with compendium and regulatory guidelines?
Plz let me know in these regards.
It is mandatory to run media fill for all pack sizes.
DeleteHi TK saha, it is find to have bracketing or matrix approach for re-validation of media fills on semi yearly basis, however it is mandate to perform media fill for all pack sizes when you are introducing a new pack into the line.
DeleteHi,
ReplyDeleteI have a weird question, why do we use SCDM only, why cannot other medias were used for media fills.
Anticipating for quick response.
Because it support the both bacterial and fungal growth.
DeleteWhy we use 3% media scdm
ReplyDelete3%SCDM is sufficient for bacteria growth.
DeleteIt is easy to filter.
It is clear and transparent
Sir, why sterile lactose used in media fill.
ReplyDelete