FDA 483 - Chromatography Institute of America, Inc. - March 05, 2023

An FDA inspection of Takeda Pharmaceutical Company Limited in Cambridge, MA, conducted from April 24 to May 5, 2023, identified several significant issues documented in an FDA Form 483. The observations primarily concerned the manufacturing of sterile drug products, specifically ADCETRIS (brentuximab vedotin) for injection, 50 mg/vial.

Key violations included a failure to adequately validate the sterilization process, evidenced by an insufficient Process Performance Qualification (PPQ) protocol for ADCETRIS. This protocol featured unrepresentative batch sizes and lacked a robust sampling plan, a deficiency previously noted in a 2017 inspection. Furthermore, the company failed to extend investigations into various batch failures—such as sterility test failures, bioburden excursions, and media fill failures—to other potentially impacted batches or products manufactured on the same filling line. Lastly, laboratory controls were found to be inadequate, as the filter validation study for ADCETRIS manufacturing did not use the actual drug product intermediate or provide sufficient justification for the chosen challenge organism. Takeda is required to implement corrective actions to address these deviations from regulatory expectations and ensure product quality and patient safety.