2. Failure to conduct appropriate microbiological testing on API batches where microbial quality is specified.In another life, I'd like to get to write angry warning letters for FDA. "You lack scientific justification" - ouch!
On March 2, 2015, we observed that all 14 culture media plates in incubator #6 were dried out and cracked, which compromised microbial growth promotion and accurate enumeration. These plates were used to test multiple API batches of [redacted] and [redacted] and [redacted].
Your investigation concluded that deformed glass plates caused the media to crack. In your response, you claimed that the issue was isolated to the 14 culture media plates and that you retested these [redacted] batches.
Your response is inadequate because your investigation did not evaluate the [redacted] other associated batches tested with culture media plates from the same lot containing deformed glass plates. In addition, we disagree with your claim that these dried culture media plates were isolated to the 14 plates we observed on March 2, 2015. On March 5, 2015, we observed two additional culture media plates in incubator SPX-150, Series No. 061103-811-0003, which also showed signs of drying out.
From 2012 to 2014, several of your customers complained that microbial results were OOS when they tested your API upon receipt. In your response, you concluded that the percentage of customer complaints reporting OOS microbial test results was insignificant. You attributed the customers’ OOS microbial results to test methods that differ from your own.
Your response lacks your findings and corrective actions from your recent investigation of dried out and cracked culture media plates. For example, you did not retest the batches that received OOS microbial complaints, even after we pointed out this deficiency. You lack scientific justification to conclude that your customers’ OOS findings are inaccurate or insignificant.
Wednesday, January 20, 2016
Warning Letter of the Week: culture plates edition
One of the things that surprises me about API manufacture (even though it shouldn't) are all the little specifications that you didn't know about. Before this FDA warning letter to Zhejiang Hisun Pharmaceutical, I didn't know there was microbial testing of API (although that certainly seems desirable and reasonable):