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MEDIA FILL
FAILURE INVESTIGATION
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Aseptic Process simulation (Media fill) is GMP requirement and is
the most sensitive method of detecting unexpected sources of process
contamination. Media fill failure is
dreaded event as it is associated with voluntary or
involuntary plant shutdowns, product recalls, and warning letters.
In the event of a process
simulation failure, a comprehensive failure investigation shall
immediately be initiated by considering all possible
causes of contamination. The investigation should have a ‘Patient - focused’ approach. During media
fill failure following actions to be initiated immediately.
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All
Contaminated units to be reconciled.
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Products
manufactured in the respective line to be quarantined.
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Production
activities on the line in question should be suspended until the completion of
media fill failure investigation.
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The potential
impact of commercial drugs produced on the line since last successful media
fill to be evaluated.
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Three prime reasons for media fill failure can
be:
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Poor personnel practice
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Loss of environmental control
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Flawed operational design
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During media fill failure investigation following details
to be verified.
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Verify all
positive containers for cracks or other integrity defects.
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Identify all micro organisms present in contaminated vials up
to species level. This will help to investigate the source of contamination.
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Possible sources
of specific organism recovered to
be identified by comparing the available data base of the organisms recently
identified from sterility tests, bioburden, and environmental monitoring
program.
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The identified contaminants should be considered for their
ability to survive in the product filled on the line were media fill failure
occurred. This approach which help to identify if sterility has been
compromised in these products. If sterility is compromised, these products
must be withdrawn from the market.
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Video tapping of the media fill to be verified to identify
personnel practices that could negatively impact on the aseptic processes.
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The investigation
should involve a review of aseptic fill data, review of component
sterilization results, review of all intervention activities, training
records of all individuals (production,
maintenance, microbiologist, cleaning etc.) and review of any
deviations, down times and repairs before or during media fill. (Elements of investigation
for failed media fill runs shall cover facility, equipment and personnel
details).
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Possible reason for media fill failure can be aseptic practices, gowning, air, dust, water, human sources, non
sterile disinfectants, water leakage, worn out garments, poor aseptic
connections, inadequate cleaning & sanitization, poor gown design, container
closure integrity problems, mechanical failure, deficient
design or control of rooms, equipment, or the Water for Injection (WFI) system
etc.
Once the source of contamination is identified, CAPA to be
initiated. After the implementation
of CAPA, a new media fill study to be performed to confirm their efficiency. Disposition of product made before
and after a failed media fill would depend up on the end results of media fill failure
investigation report.
