FDA WARNING_LETTER - Fresenius Kabi Oncology Limited (Baddi) - April 14, 2017

The FDA inspected Fresenius Kabi Oncology Limited's Baddi, India facility from April 6-14, 2017, identifying significant CGMP violations, rendering their drug products adulterated. The primary violation was the failure to thoroughly investigate a sterility failure for (b)(4) injection (lot (b)(4)), which showed Bacillus subtilis, Pseudomonas putida, and Pseudomonas entomophila growth during stability testing. The company's investigation attributed this to laboratory error (insufficient sporicidal disinfection during sample transfer), but the FDA found this inadequate given multiple subsequent disinfection steps, use of a (b)(4) filtration system within an ISO-5 cRABS, negative controls, no observed aseptic breaches, and stable environmental monitoring.

The FDA noted the investigation failed to address potential manufacturing root causes, including long-term environmental data trends, atypical gram-negative bacteria findings in the production cRABS earlier in the year, and the company's history of attributing sterility positives to poor material disinfection. This issue of inadequate investigations into out-of-specification results is recurring, with a similar observation cited in a May 2015 inspection and another Warning Letter issued on December 4, 2017.

Required corrective actions include: ensuring future sterility failure investigations thoroughly review long-term trends, manufacturing vulnerabilities, and correlations with past incidents; assessing the overall investigation system for deviations and failures with a CAPA plan; detailing sporicidal immersion procedures