Regeneron Ireland Designated Activity Company – FDA 483, Mar 14, 2023

The FDA Form 483 inspection identified significant deficiencies in the quality unit's control over documents and data integrity, as well as issues with testing procedures, environmental monitoring, and data review.

**Observation 1** details that original GMP forms are routinely discarded if mistakes occur, with data rewritten onto new forms, violating SOP-GE1008. While an audit trail exists for printed forms, it's not reviewed, and forms are not reconciled. Shredders and confidential bins are accessible, and discarded original GMP forms were found, including partially completed templates and checklists. The practice of scanning original forms and discarding them, with no quality oversight for completeness or accuracy, was noted, with illegible scans observed. Furthermore, the procedure allowing printing, wet signing, rescanning, and discarding of documents with original signatures lacks authentication. Uncontrolled "templates" are used and discarded, with the quality unit unaware of their full extent.

**Observation 2** states that scientifically sound test procedures are not followed, specifically regarding manual integration for chromatography and capillary electrophoresis. Procedures requiring optimization attempts before manual integration are not documented or adequately reviewed.

**Observation 5** highlights issues with air handling systems. ISO 5 classified areas lack non-viable particle data during dynamic operations to demonstrate compliance. HEPA filter failures are handled as "Notice of Event" (NOE) without root cause investigations, despite 9 failures since May 2021 identifying filter damage.

**Observation 6