FDA 483 - Fukuzyu Pharmaceutical Co., Ltd. - January 15, 2024

During an inspection conducted from January 15-19, 2024, the FDA issued a Form 483 to Fukuzyu Pharmaceutical Co., Ltd., an API manufacturer in Toyama, Japan. The document highlighted significant concerns regarding the firm's adherence to Current Good Manufacturing Practices (CGMP).

Several critical observations were noted. Firstly, the quality unit's investigations into out-of-specification (OOS) results and critical deviations were deemed inadequate, lacking scientific justification for root causes and failing to assess the impact on previous product lots. For instance, OOS investigations for assay and residual solvent content were closed without thorough scientific backing or adequate corrective actions, leading to the distribution of potentially non-conforming batches.

Secondly, the firm"s procedures for preventing cross-contamination were deficient. Shared production equipment was observed with apparent residue after cleaning, and its cleaning validation was incomplete, particularly concerning hazardous substances. The validation study itself exhibited issues with standard solution stability, yet the report was approved without proper investigation.

Thirdly, the validation of in-house analytical methods, such as the gas chromatography method for residual solvents, was incomplete, casting doubt on the reliability of release testing.

Finally, the control of computerized systems and electronic records in the QC laboratory demonstrated significant data integrity vulnerabilities. A single administrator possessed unlimited power to modify or delete electronic records, and older systems lacked essential features like forced data saving and audit trails, with data being transferred via unsecure floppy disks.

Fukuzyu Pharmaceutical is expected to thoroughly address these observations to ensure compliance with regulatory standards and maintain product quality and integrity.