FDA 483 - Alembic Pharmaceuticals Limited - March 20, 2018

This FDA Form 483 details observations from an inspection, highlighting significant quality system and manufacturing deficiencies.

**Observation 1** cites a failure to thoroughly review unexplained discrepancies and Out-of-Specification (OOS) results. The firm exhibited high OOS invalidation rates: 94% in 2016 (131 of 140), 91% in 2017 (117 of 129), and 63% in early 2018 (19 of 30). Examples of invalidated OOS results lacking scientific rationale and supporting documentation include: * OOS #ALP/QA/OOS-8042 (high assay for Tablets USP mg): Attributed to sample preparation error, unsupported by re-injection/re-filled results. * OOS #ALP/QA/OOS-8027 (OOS impurity for Capsules USP mg): Attributed to glassware contamination, unsupported as all samples failed. Other contamination sources were not investigated. * OOS #ALP/QA/OOS-8058 (low assay for Tablets USP mg/ng): Attributed to sample preparation error, but repeat analysis deviated from the method, and preventative measures were inadequate. * OOS #ALP/QA/OOS-6491 (high assay for Tablets USP mg validation batch): Attributed to dilution error,