Takeda Pharmaceutical Company Limited – FDA 483, Nov 6, 2023

The FDA Form 483 details observations from an inspection, indicating deficiencies in quality systems and manufacturing processes.

**Observation 1** highlights a failure to investigate unexplained discrepancies and batch failures. Specifically, the facility did not initiate comprehensive investigations into a negative trend of critical quality complaints for a drug/device product. This led to a failure to implement corrective and preventive actions (CAPA) for recurring defects, citing examples of seven complaints for one lot of sterile injectable product and six for another lot with device component issues.

**Observation 2** notes a failure to thoroughly review unexplained discrepancies or batch failures. The Quality Unit did not initiate or consider additional evaluations of sterile injectable products when action limits were reached during visual inspection, as described in SOP no. 225372 "Visual Inspection of Drugs for Injection."

**Observation 3** identifies deficiencies in the environmental monitoring system for aseptic processing areas. A non-viable particle counter was approximately [redacted] away from the [redacted] during [redacted] filling operations, as observed during a review of the "EM Risk Assessment and EM Performance Qualification for [redacted] Manufacturing Line."

**Observation 4** indicates that batches of drug product required to be free of objectionable microorganisms are not adequately tested. On October 31, 2023, a microbiologist performing Endotoxin Testing for [redacted] Lot [redacted] (manufactured October 28, 2023