FDA 483 - Chugai Pharma Manufacturing Co., Ltd., Ukima Plant - August 23, 2021

An FDA Form 483 was issued to Chugai Pharma Manufacturing Co., Ltd.'s Ukima Plant in Tokyo, Japan, following an inspection conducted from August 17 to August 23, 2021. The observations highlight significant deficiencies in the facility's adherence to current Good Manufacturing Practices (cGMP) for drug substance manufacturing. Key issues included a lack of assurance regarding the effectiveness of cleaning procedures for product-contact equipment, specifically concerning validation methods, swab location justification, and thorough investigation of cleaning parameters. Data integrity was also compromised, with computerized systems for data acquisition and validation lacking proper validation to protect electronic records and audit trails. Furthermore, Standard Operating Procedures (SOPs) for sample collection and material handling were either not followed or were found inadequate. The inspection also identified a deficient cleaning and sanitization program, noting that disinfectant efficacy studies were insufficient, and documentation of contact times was not required. Issues with sample stability studies and the inadequate qualification of critical clean utilities, such as utility sampling and testing at points of use, were also raised. Chugai Pharma Manufacturing Co., Ltd. is required to address these observations by conducting thorough investigations, implementing robust corrective and preventive actions, and submitting a comprehensive response to the FDA to demonstrate compliance with regulatory standards.