FDA 483 - Sanofi Pasteur Inc. - January 26, 2024

An FDA inspection conducted from January 18 to January 26, 2024, at a pharmaceutical firm in Val de Reuil, France, identified several significant manufacturing deficiencies, documented in an FDA Form 483. The inspection highlighted a critical failure in aseptic process validation, specifically concerning sterile drug products. An aseptic process simulation for a lyophilizer line failed due to mold contamination (Engyodontium album), affecting two batches of the US-licensed Dengvaxia® vaccine. Subsequent attempts to requalify the line were also unsuccessful or incomplete. Further issues included the quality control unit's failure to adhere to its own procedures, with 12 out of 30 reviewed deviations not being initiated within the required timeframe. The facility's infrastructure was also cited, as a Grade B aseptic area floor exhibited cracks, non-uniform sealant, and a gap, lacking proper risk assessment and environmental monitoring to ensure cleanliness and suitability for sterile manufacturing. Lastly, a visual inspection machine used for Dengvaxia® was found to have differing acceptance criteria in its requalification protocol compared to the product's actual visual inspection procedure. These observations indicate potential non-compliance with current Good Manufacturing Practices (cGMP), necessitating a comprehensive response and corrective actions from the firm.