FDA 483 - Takeda Manufacturing Singapore Pte. Ltd. - November 18, 2022

During an inspection conducted from November 10-18, 2022, the U.S. Food and Drug Administration (FDA) issued a Form 483 to Takeda Manufacturing Singapore Pte. Ltd., a licensed biological manufacturer. The observations detailed significant concerns regarding the firm's adherence to current Good Manufacturing Practices (cGMP). The primary issues centered on two key areas. Firstly, the company exhibited shortcomings in its investigation of unexplained discrepancies. Multiple instances were cited where negative trends or atypical results lacked identified root causes, immediate corrections, further investigations, or properly initiated Corrective and Preventive Actions (CAPAs). In some cases, the justification for not performing effectiveness checks on implemented changes was deemed insufficient. Secondly, the FDA noted deficiencies in the quality control unit's responsibilities, particularly concerning Good Documentation Practices (GDP) and data integrity. Inadequate training and procedures led to several critical incidents, including missing security audit trails, lost electronic test files, un-saved data, discrepancies between electronic and hardcopy records, and process control system failures due to human error during calibration. These observations indicate a need for comprehensive improvements in Takeda's quality system, particularly in discrepancy management, data integrity, and employee training. The company is required to thoroughly address these findings by developing and implementing robust corrective and preventive actions to ensure compliance with regulatory standards.