FDA WARNING_LETTER - Lupin Limited - May 19, 2017

The FDA issued a Warning Letter to Lupin Limited following inspections of their Goa (March-April 2017) and Indore (May 2017) drug manufacturing facilities, citing significant Current Good Manufacturing Practice (CGMP) violations, rendering their drug products adulterated.

At Lupin Goa, violations included inadequate investigation of Out-of-Specification (OOS) results, particularly invalidating initial OOS lab results without thorough investigation into manufacturing causes. Examples cited were an API assay failure where multiple retests confirmed the OOS result, yet it was invalidated as an "outlier," and content uniformity failures for tablets where laboratory error was surmised without conclusive evidence or investigation into manufacturing causes. The firm also failed to establish appropriate time limits for production phases, holding bulk materials for excessive periods without adequate hold time studies representative of commercial batch sizes.

At Lupin Indore, similar violations were identified: inadequate hold time studies for bulk materials, not representative of commercial operations, and invalidation of nearly all initial OOS results (134 of 139 from 2015-2016) by attributing them to laboratory error without thorough investigation into potential manufacturing causes. An example included discarding an OOS sample vial and invalidating results based on retests without investigating manufacturing issues.

The FDA noted these were repeat observations at both sites, indicating inadequate company-wide oversight. Lupin's responses were deemed insufficient, lacking comprehensive retrospective assessments and robust corrective actions.

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