FDA WARNING_LETTER - Genzyme Corporation - July 09, 2024

The FDA issued an amended Warning Letter to Genzyme Corporation (a Sanofi subsidiary) following an inspection from June 12 to July 9, 2024, at their Framingham, MA facility. The letter identifies significant deviations from Current Good Manufacturing Practice (CGMP) for active pharmaceutical ingredients (APIs), rendering their APIs adulterated under 21 U.S.C. 351(a)(2)(B).

Key violations include: 1. **Failure to investigate all critical deviations:** Approximately 20% of bioreactor runs between January 2022 and July 2024 were rejected due to contamination or quality failures. Specific examples include inadequate investigations into OOS appearance for two lots of (b)(4) and three lots of (b)(4) due to (b)(4) particles, and three in-process high-pressure events with product leakage. The firm's response was deemed inadequate for not providing completed investigations, root causes, or justification/effectiveness determination for CAPAs. 2. **Failure to demonstrate reproducible API manufacturing:** The firm repeatedly deviated from validated manufacturing processes, such as performing (b)(4) of the (b)(4) during (b)(4) bioreactor runs, despite the process being validated with (b)(4) and increasing contamination risk. Manufacturing personnel also used a "Pre-Job Briefing" to deviate from validated procedures by replacing a (b