FDA 483 - Fukuzuyu Pharmaceutical Co., Ltd. - January 19, 2024

An FDA inspection conducted from January 15-19, 2024, at an unnamed pharmaceutical manufacturing firm, identified significant deviations from manufacturing quality standards. The Senior Managing Director, Tetsuaki Nishinaga, received a Form FDA 483 outlining four key observations.

Firstly, the quality unit demonstrated inadequate investigation into out-of-specification (OOS) results and critical deviations. Investigations for assay and residual solvent OOS results lacked scientific justification for conclusions and subsequent corrective actions, with batches released despite insufficient root cause analysis and a history of similar issues.

Secondly, shared production equipment was not consistently cleaned and maintained to prevent cross-contamination, particularly between non-hazardous APIs and hazardous substances. Residue was observed in "clean" equipment, and cleaning procedures were not validated for inactivating all hazardous residues. Furthermore, critical standard solutions for cleaning validation failed stability criteria but were still used without proper investigation.

Thirdly, analytical method validation was incomplete, with no documentation for the in-house gas chromatography method used for API release testing.

Finally, control over computerized systems and electronic records in the QC laboratory was deficient. A single individual with oversight of API release had unlimited administrative access to critical software, posing a data integrity risk. Additionally, an integrator system lacked essential data integrity features like forced saving, audit trails, and secure data storage, relying on unsecure floppy disk transfers.

The company is required to thoroughly address these observations to ensure compliance with regulatory standards.