FDA 483 - Laboratorios Farmaceuticos Rovi S. A. - June 27, 2022

The FDA Form 483 document outlines several observations from an inspection of a facility involved in the commercial manufacturing of mg and mg Injection.

**Observation 1** details deficiencies in investigation procedures. Investigations into unexplained discrepancies and out-of-specification (OOS) results for the commercial manufacturing process, particularly concerning Human Machine Interface (HMI) performance issues, lacked conclusions and follow-up. Specifically, HMI "blocked" issues leading to filling operation stoppages (Deviations UDMI-NOT-22-120 and UDMI-INV-22-041) remained open, preventing observation of manufacturing. Additionally, OOS microbiology test results for packaging components (e.g., OOS No. QOS-MC-20-010 and OOS No. OOS-MC-20-020) lacked corrective/preventive actions (CAPAs) despite root cause determinations. The firm also failed to thoroughly review unexplained discrepancies, even for distributed batches.

**Observation 2** indicates that procedures to prevent microbiological contamination of sterile drug products were not followed. The aseptic filling process validation (UDMI-PMV-21-013/00, UDMI-IVP-22-010) was inadequate, as only 3 out of many production operators performed "corrective interventions" during process simulation, and these operators did not appear adequately qualified.

**Observation 3**