Thursday, 12 November 2015

Media Fill Failure Investigation


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.

All Contaminated units to be reconciled.
Products manufactured in the respective line to be quarantined.
Production activities on the line in question should be suspended until the completion of media fill failure investigation.
The potential impact of commercial drugs produced on the line since last successful media fill to be evaluated.

Three prime reasons for media fill failure can be:
Poor personnel practice
Loss of environmental control
Flawed operational design

During media fill failure investigation following details to be verified.

Verify all positive containers for cracks or other integrity defects.
Identify all micro organisms present in contaminated vials up to species level. This will help to investigate the source of contamination.
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.
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 If sterility is compromised, these products must  be withdrawn from the market.
Video tapping of the media fill to be verified to identify personnel practices that could negatively impact on the aseptic processes.

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).

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.

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