FDA EIR - Takeda Pharmaceutical Company Limited - November 26, 2019

An FDA inspection of Takeda Pharmaceutical Company Limited in Hikari, Japan, was conducted from November 18 to November 26, 2019. This comprehensive Current Good Manufacturing Practice (cGMP) inspection of their sterile drug manufacturing operations, initially abbreviated but expanded due to significant findings, identified fourteen observations cited on an FDA-483 form. Key issues included inadequate quality unit oversight, failures in controlling manufacturing processes, and insufficient investigation into product quality deviations such as metal particles and sterility failures. The facility also demonstrated deficiencies in aseptic controls, including poorly designed or absent aseptic process simulations, and a critical failure to re-qualify a stopper washer for endotoxin removal since 1997. Further concerns involved inadequate procedures for filter integrity testing, improper handling and sterilization of gowns and wipes, and overall poor aseptic practices during filling operations. In response to the findings, Mr. Hideki Fujiwara, Head of Hikari Plant, committed to implementing corrective actions and providing a formal written response to the FDA within 15 business days, underscoring the need for improved adherence to regulatory expectations for sterile drug manufacturing.