Lupin Limited – FDA Warning Letter, Apr 4, 2022

The FDA issued a Warning Letter to Lupin Limited following an inspection of their API manufacturing facility in Tarapur, India, from March 22 to April 4, 2022. The inspection revealed significant deviations from current Good Manufacturing Practice (CGMP) for active pharmaceutical ingredients (API), rendering their API adulterated. The company's April 25, 2022, response to the FDA 483 was deemed inadequate.

Key violations include: 1. **Failure to establish adequate written procedures for cleaning equipment:** The firm's risk assessments for cleaning effectiveness lacked data to support the removal of genotoxic impurities and residual API. Conflicting data regarding genotoxic impurity detection was disregarded without scientific justification. The company committed to dedicating equipment for certain APIs but not for solvent recovery tanks, leaving cross-contamination risks. The FDA requires a comprehensive, independent retrospective assessment of cleaning effectiveness, a CAPA plan, and improvements to the cleaning validation program, including worst-case scenario considerations. 2. **Failure to establish written procedures to monitor processing steps:** The manufacturing process for certain APIs resulted in quantifiable levels of a genotoxic impurity at irregular frequencies, despite studies concluding effective purging. The firm failed to investigate these occurrences. The FDA requires an investigation into genotoxic impurity formation, data from process capability analysis, and a risk-based review procedure for all manufactured products. 3. **Failure to investigate all critical deviations:** An out-of-specification