FDA EIR - Bayer AG - July 27, 2020

An FDA international for-cause and current Good Manufacturing Practice (CGMP) inspection of Bayer AG's facility in Leverkusen, Germany, took place from July 20-27, 2020. The inspection, guided by CPGM 7356.002 and 7356.002F for drug and API manufacturing, identified several significant issues resulting in the issuance of an FDA-483. Key observations included incomplete investigation records for unexplained discrepancies, particularly regarding microbial excursions within the water system, where root causes were not fully determined, and regular sanitization schedules were absent. The manufacturing processes for certain drug products and active pharmaceutical ingredients (APIs), along with associated equipment cleaning validation, were not consistently demonstrated to be in a state of control. This encompassed concerns such as unvalidated physical process parameters for the water system and lack of scientific justification for worst-case cleaning validation points. Additionally, potential cross-contamination risks were noted from inadequately filtered air exhaust originating from tablet manufacturing operations. Dedicated equipment was found with fibrous material and distressed gasket material post-cleaning, indicating insufficient maintenance and cleaning effectiveness. Finally, the firm's Out-of-Specification (OOS) procedures allowed retesting and substitution of original OOS data without scientific justification, though this procedure was rectified during the inspection. Bayer AG management assured the FDA of a formal response within 15 working days and committed to implementing corrections to address all identified observations, ensuring adherence to the Food, Drug and Cosmetic Act.