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

The FDA issued a Warning Letter to Takeda Pharmaceutical Company Limited following an inspection from November 18-26, 2019, at their Hikari, Yamaguchi facility. The letter identifies significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals, rendering their drug products adulterated under the FD&C Act. The company's December 18, 2019, response to the FDA 483 was deemed inadequate.

Key violations include: 1. **Inadequate Quality Control Unit (QCU) procedures (21 CFR 211.22(d)):** The QCU allowed aseptic manufacturing to resume after a shutdown without performing a required aseptic process simulation (media fill), leading to the shipment of affected batches to the U.S. market. The FDA requires a comprehensive assessment of the QCU's authority and resources, oversight provisions, batch review processes, and a risk assessment of distributed products. 2. **Failure to establish and follow appropriate written procedures for preventing microbiological contamination (21 CFR 211.113(b)):** * **Inadequate Aseptic Processing Simulations (Media Fills):** The media fill program lacked assurance of preventing microbial contamination, with integral units removed from media fills without adequate justification and insufficient incorporation of commercial production risks, such as the manually intensive (b)(4) operation. * **Poor Aseptic Behavior:** Operators