FDA 483 - Chugai Pharma Manufacturing Co. Ltd. (CPMC) - February 21, 2020

During an inspection from February 13-21, 2020, the U.S. Food and Drug Administration (FDA) issued a Form 483 to Chugai Pharma Manufacturing Co. Ltd, a drug product manufacturer located in Utsunomiya, Tochigi, Japan. The document detailed observations indicating potential non-compliance with regulatory standards under the Federal Food, Drug, and Cosmetic Act. Key issues identified centered on the prevention of microbiological contamination and the validation of test methods for sterile drug products. Specifically, the firm failed to establish and adhere to appropriate written procedures for preventing contamination, including a lack of comprehensive validation for aseptic and sterilization processes. This involved insufficient media fill runs for a critical filling line, which did not adequately simulate worst-case production conditions like sterile hold times or aseptic filling durations. Additionally, multiple test methods were found to be inadequately validated or verified. Examples included the execution of sterility and bioburden method suitability tests at an alternate site, and inconsistencies observed during integrity and leak tests for equipment, often without proper documentation of deviation root causes. Chugai Pharma Manufacturing Co. Ltd is expected to review these findings and implement corrective and preventive actions to ensure full compliance and maintain product quality.