FDA 483 - Toyobo Co. Ltd. - February 25, 2023

During an inspection conducted from February 15-25, 2023, the U.S. Food and Drug Administration (FDA) issued a Form 483 to Toyobo, Co., LTD, a sterile drug manufacturer located in Otsu, Shiga, Japan. The observations highlight significant deficiencies in the company's manufacturing and quality control processes, indicating a need for adherence to Good Manufacturing Practices (GMP) regulations. Key issues included inadequate validation of aseptic sterilization processes, specifically regarding unidirectional air flow evaluations (smoke studies) which were deemed insufficient in duration or technique. The inspection also identified a failure to establish comprehensive written procedures for production controls, particularly concerning the light shielding requirements for a critical active pharmaceutical ingredient (API) during manufacturing, lacking documented exposure times or technician records. Furthermore, laboratory controls were found deficient, with bacterial endotoxin testing not adhering to best practices, as only one vial per batch was tested instead of a minimum of three, and vials were not vortexed prior to analysis, potentially affecting accuracy. Procedures to prevent microbiological contamination in sterile areas were either not established, inadequately written, or not followed, including insufficient sterile cleaning instructions and observed inappropriate personnel behavior during sterile filling operations. Finally, the company failed to consistently follow its own quality information and defect handling procedures, specifically regarding complaint documentation and historical review of similar quality issues. Toyobo, Co., LTD is required to review these observations and implement appropriate corrective actions to ensure compliance.