FDA 483 - Catalent Belgium SA - August 19, 2022

This FDA Form 483 details multiple deficiencies observed during an inspection of a facility manufacturing drug products for the US commercial market, including a combination drug/device.

Key observations include: - **Aseptic Processing Areas:** Air visualization studies in RABs failed to demonstrate sufficient airflow velocity over critical areas of filling machines, particularly during interventions. - **Deviation Investigations:** The firm failed to thoroughly review unexplained discrepancies and perform proper root cause analysis for sterilizing equipment issues, despite recurring observations of sterilized part contamination between 2019 and 2021. - **Process Control:** Aseptic filling process simulations (media fills) performed after significant HVAC changes were deficient, failing to consider major changes to HEPA filters and not simulating worst-case conditions (larger openings, low filling speed). - **Equipment Qualification:** - Sterilization cycle requalification used incorrect part types. - Integrity tester performance qualification studies were deficient, with incorrect study parameters and potential for false negatives. - Integrity test results were recorded as Pass/Fail without numerical values or initial/final pressure records. - Equipment clean hold time studies were deficient, not demonstrating cleanliness after a single cleaning cycle. - Climate-controlled chamber qualifications (stability chambers, refrigerators, incubators) were deficient, lacking recorded temperature/humidity recovery times. - **Data Integrity:** - QC instruments and equipment lacked protection from manipulation; procedures allowed analysts to change date and