FDA WARNING_LETTER - Emcure Pharmaceuticals Limited - February 20, 2019

The FDA inspected Emcure Pharmaceuticals Limited in Pune, India, from February 11-20, 2019, identifying significant CGMP violations for finished pharmaceuticals, rendering drug products adulterated. The primary violation was the failure to thoroughly investigate unexplained discrepancies or failures of batches to meet specifications (21 CFR 211.192).

Specifically, the firm inadequately investigated sterility failures for two injection batches in 2017 and 2018, attributing them to laboratory error without sufficient supporting data. Investigations failed to adequately address potential manufacturing causes, despite the same microorganisms (Lysinbacillus fusiformis and Bacillus cereus) being found in production areas prior to the sterility failures. The firm's review of environmental data was insufficient, focusing too heavily on the laboratory and neglecting production failure modes, particularly container-closure integrity hazards. The company had previously recalled products due to container-closure integrity failures.

The FDA acknowledged the firm's recall of distributed sub-lots and commitment to install a sterility test isolator and review investigation procedures. However, the letter requires a comprehensive assessment of the firm's investigation system, a third-party evaluation of records related to sealing variability and container-closure integrity since July 2016, and plans to ensure future sterility failure investigations include manufacturing vulnerabilities like sterilizer uniformity and container-closure system integrity. A third-party review of sterility test methods to eliminate false turbid readings and a review of steril