FDA 483 - Wyeth BioPharma Division of Wyeth Pharmaceuticals LLC - July 23, 2021

During an inspection conducted from July 19-23, 2021, the FDA issued a Form 483 to Wyeth BioPharma Division of Wyeth Pharmaceuticals LLC, a drug substance manufacturer in Andover, MA. This document details significant observations indicating conditions and practices that may not comply with Current Good Manufacturing Practice (CGMP) regulations, as outlined under Section 704(b) of the Federal Food, Drug, and Cosmetic Act. Key violations centered on inadequate quality control and oversight. Specifically, insufficient data supported the release of BNT162b2 drug substance batches that deviated from validated processes, with delayed stability testing. Quality assurance failed to review critical electronic data and overlooked batch record discrepancies. Deviation investigations were found deficient, particularly concerning particulate matter. Further concerns included unvalidated cleaning processes, inadequate cleaning efficacy studies, and poor environmental control within ISO-classified areas, including improper monitoring and a deficient environmental monitoring program. The facility experienced compromised cleanroom conditions due to HVAC shutdowns, yet drug substance was processed and released without verifying the room's clean state. Operators frequently deviated from Standard Operating Procedures during manufacturing, cleaning, and material handling. Additionally, the facility exhibited maintenance issues like mold, dust, residue, and structural gaps, along with improper storage of raw materials. Wyeth BioPharma is now expected to provide a robust response detailing corrective and preventive actions to address these systemic quality and compliance issues.