FDA 483 - Eisai Co., Ltd. Kashima Plant - November 18, 2022

An FDA inspection at Eisai Co., Ltd. Kashima Plant, an Active Pharmaceutical Ingredients manufacturer in Japan, from November 14-18, 2022, identified significant deviations from current Good Manufacturing Practices (cGMP). The inspection revealed inadequate controls over critical computer systems used for testing raw materials, intermediates, and APIs. Specific issues included the ability to make unauthorized changes to dates/times on a Karl Fischer system, and the deletion or renaming of raw data on TOC meters and HPLC systems without proper audit trail reviews. The firm also failed to consistently calculate actual and theoretical yields for API manufacturing phases, lacked scientific justification for yield acceptance ranges, and did not record actual sample weights during collection. Furthermore, labeling operations demonstrated a lack of strict control, with manufacturing staff able to print finished API labels without Quality Unit oversight. Finally, concerns were raised regarding the storage of materials, noting discrepancies in refrigerated warehouse temperature monitoring and a complete lack of temperature or humidity control in other raw material warehouses. Eisai Co., Ltd. is required to implement comprehensive corrective actions to address these observations and ensure product quality and regulatory compliance.