FDA 483 - Sanofi Winthrop Industrie - May 25, 2018

An FDA inspection conducted at Sanofi Winthrop Industrie, a vaccines and pharmaceutical drugs manufacturer in Le Trait, France, from May 16 to May 25, 2018, identified significant deficiencies in their manufacturing and quality control systems. The observations, made under the Federal Food, Drug, and Cosmetic Act, highlight multiple areas requiring immediate corrective action to ensure compliance with current Good Manufacturing Practices (cGMP).Key violations include pervasive issues within aseptic processing areas. There were numerous high-efficiency particulate air (HEPA) filter integrity failures and recurrent environmental monitoring excursions (both viable and non-viable), impacting critical drug products like Lovenox and Praluent. Equipment in these sterile areas showed frequent malfunctions, including loose components and aseptic barrier breaches. Furthermore, media fill simulations were deemed inadequate, failing to represent actual production interventions, and environmental monitoring protocols were insufficient. The inspection also cited poor control over materials, with rejected products and labeling materials stored insecurely or inappropriately alongside active ingredients, and inadequate access controls. Packaging and labeling operations demonstrated a history of line clearance failures, leading to product mix-ups across different batches. Deficiencies extended to quality assurance, with inadequate training for visual inspection personnel and concerns regarding the validation of automated inspection equipment. The complaint handling system was found lacking, failing to trigger adequate investigations for recurring issues, such as the persistent "Praluent Plunger Difficult to Depress" complaints, which notably increased since a previous inspection. Finally, critical quality system procedures for Corrective and Preventive Actions (CAPA) and Out of Specification (OOS) investigations were deemed inadequate, lacking essential details like completion timeframes or clear process flows. Sanofi Winthrop Industrie must implement comprehensive corrective and preventive actions to resolve these systemic issues.