Warning Letter McGuff Pharmaceuticals CGMP Violations 12/28/10

McGuff Pharmaceuticals Inc 12/28/10

Warning Letter

CGMP Violations

1.  Your firm has not thoroughly investigated the failure of a batch or any of its components to meet its specifications whether or not the batch has already been distributed [21 C.F.R. §211.192]

For example, your firm failed to conduct adequate investigations into action level excursions.  Your investigations (e.g., (b)(4) of growth in a media fill did not include a review of the batch records, equipment logs, or HVAC system by the most responsible personnel (e.g., a microbiologist reviewed a batch record).  Further, the Quality Assurance Unit did not review and approve the investigation.  Finally, your firm failed to implement the corrective/preventative action identified in the investigation.

In your response, your firm states that: 1) your SOP will be revised to require a formal investigation by the Quality Assurance Unit when environmental monitoring action levels are exceeded and 2) retrospective investigations into previous excursions were conducted.  You also commit to re-investigate (b)(4) and that any impact on aseptic operations will be assessed by the Quality Assurance Unit.  Your response, however, is inadequate because you have not described how you will assess the potential impact on products that have already been distributed.

COMMENTS

Growth within a media fill either during the initial validation of three successive successful media fills or a periodic media requalification should contain no more than two test positives.  However, regardless of the number of test positives, each media fill should be investigated to attempt to determine the root cause of the cause of the microbial growth.  The information, as noted above, should be reviewed by an individual skilled in this area, e.g., a microbiologist.  Even with a microbiologist’s review, the results should be approved by the Quality Assurance Unit. 

The potential impact on products that have previously been distributed remains quite difficult when it has been noted that environmental monitoring action levels have been exceeded, but no data has been collected or data collected has been inadequately reviewed.  If microbial identifications had been made (unknown to writer), then it may be possible to determine the magnitude of the hazard.