APOTEX INC RECEIVES WARNING LETTER FOR MULTIPLE CANADIAN SITES (2/21/13) PART II

FDA INVESTIGATOR FINDS INACCURATE REPORTING OF MICROBIOLOGICAL DATA

The FDA, during August and October 2012 inspected two Apotex, Inc. sites.  This Blog only discusses the facilities located at 150 Signet Drive, Toronto, Canada.  The U.S. Food and Drug Administration (FDA) identified significant violations of current good manufacturing practice (CGMP) regulations during the audit for finished pharmaceuticals, Title 21, Code of Federal Regulations, Part 210 and 211.

Observation 1 was previously discussed earlier this week.  Observation 3, another relating to microbiology, is noted below.

“3. Your firm failed to ensure that laboratory records included complete data derived from all tests necessary to assure compliance with established specifications and standards (21 CFR 211.194(a)).

For example, on August 22, 2012, an FDA investigator observed your microbiologist reading an environmental monitoring (personnel) plate. The microbiologist reported the result for that plate as zero; however, our FDA investigator observed one (1) colony forming unit (CFU) on the plate.  Your microbiologist corrected this observation on the form WI-MI-150-108-J Microbiology Laboratory after the FDA investigator pointed it out to him.  Your firm did not take further action to investigate and determine the impact of inaccurate reporting of your microbiological plate readings on the release of your batches.

The failure to document positive results for a microbial plate that was confirmed as containing microbial growth raises concerns about the accurate reporting of results in your records.  Accurate and reliable microbial data management is essential to support the reliability of your aseptic manufacturing of finished drug products intended for distribution in the United States.

COMMENT

An investigation and determination of the impact of inaccurate reporting of microbiological plate readings on the release of batches is essential – especially when a FDA investigator, during an investigation of the Client’s site, discovers a non-conformance that the on-site microbiologist has failed to notice.  

As noted within the FDA commentary associated with this Observation, “the failure to document positive results for a microbial plate that was confirmed as containing microbial growth raises concerns about the accurate reporting of results in your records.  Accurate and reliable microbial data management is essential to support the reliability of your aseptic manufacturing of finished drug products intended for distribution in the United States.” 

While the information listed within this Observation does not specify where the positive was observed –only that it came from an “environmental monitoring personnel plate”, the Investigator deemed the missed count to be sufficiently significant to ultimately raise the concern to the level of an Observation within a Warning Letter.  The information provided is insufficient to determine whether it was obtained during a critical operation.  However, the assumption is that it was obtained from an ISO 5 environment. 

The concern regarding the missing of counts within controlled and classified environments has a predecessor within several other Warning Letters that have previously appeared within this Blog.  Within these individual Blogs, several Indian companies, one of which was located in India and the other which was located in Mexico, were cited for having “nil” colonies, where the term “nil” suggested zero counts.  The FDA Investigator, however, noted in both of these situations that bacteria were actually present.  For additional information please review the Cadia Healthcare Ltd India (July 19, 2011) and the Aurobindo Pharma Ltd (August 22, 2011) Blogs that were presented within my WordPress site.