FDA 483 - Aptuit Ltd - February 25, 2020

The FDA Form 483 details multiple deficiencies at a pharmaceutical manufacturing facility. The Quality Unit failed to ensure cGMP compliance, lacking adequate assessments and personnel expertise. This is evidenced by classifying all complaints and QC incidents as 'minor' since 2017/2018, invalidating failing/OOS results without scientific justification, and an unscientific in-process sampling procedure.

The firm repeatedly failed to implement CAPAs for recurring coring/fragmentation complaints in vials, with approximately 11 confirmed complaints lacking documented corrective action. A thorough trend analysis for mg/vial lots was not conducted, leading to release of batches with assay results at specification extremes, indicating a non-robust manufacturing process.

Investigations into unexplained discrepancies and OOS results were inadequate. The Quality Unit did not thoroughly assess consumer complaints regarding particles, appearance, closure integrity, and low fill in sterile injectable products. Specifically, a systematic trend of particulate complaints lacked thorough assessment and timely CAPAs.

Vials were observed to be improperly sealed, and while an unplanned deviation was initiated, the firm concluded it might be an isolated case without subjecting control samples to seal tightness or non-destructive leak tests. OOS investigations frequently invalidated failing results based on re-sampling and retesting, often without scientific justification or root cause identification, and without implementing CAPAs. Examples include OOS reports for particulate matter, analyst errors, and unknown impurities, where retesting yielded favorable results despite no definitive root cause.