FDA 483 - AGC WAKASA CHEMICALS CO., LTD. - November 02, 2023

During an inspection conducted from October 30 to November 2, 2023, the FDA identified significant quality control deficiencies at AGC Wakasa Chemicals Co., Ltd., an API and intermediate manufacturer located in Obama, Fukui, Japan. The observations detailed in the Form FDA 483 highlight several areas requiring immediate attention to ensure compliance with quality standards. A primary concern was the firm's Quality System, where deviations, particularly Out-of-Specification (OOS) results, were not adequately investigated or followed up with appropriate corrective actions. Investigations into OOS findings for product assays lacked thoroughness, failed to explore manufacturing records, and did not scientifically validate hypothesized root causes like static electricity from low humidity, leading to invalidation of initial OOS data without proper resolution. Furthermore, the Production System revealed issues with personnel training. Employees performing critical visual inspections of finished Active Pharmaceutical Ingredients (APIs) were found not to be following established procedures during qualification, completing inspections much faster than required. The qualification process itself was flawed, using inappropriate test parameters and lacking challenges for various defect types. The firm also demonstrated inadequate control over batch record issuance, relying on memory rather than a robust tracking system. Lastly, the Laboratory System exhibited a failure in ensuring scientifically justified and appropriate analytical procedures. Specifically, methods for microbial testing of water used in API manufacture were not validated. These observations indicate a need for AGC Wakasa Chemicals Co., Ltd. to implement comprehensive corrective and preventive actions to address systemic quality and operational shortcomings.