FDA 483 - Toyobo Co. Ltd. - January 23, 2018

During an inspection conducted from January 15-23, 2018, the U.S. Food and Drug Administration (FDA) issued a Form 483 to Toyobo Co., Ltd, Otsu Pharmaceuticals Plant, a drug product manufacturer located in Otsu-Shi, Shiga, Japan. This document outlines significant observations indicating potential deviations from Current Good Manufacturing Practices (CGMP) designed to ensure drug product quality and safety. The primary issues identified revolved around severe data integrity failures, with 41 instances between 2008 and 2015 impacting various laboratory test results. The firm's corrective actions for these integrity issues were found to be ineffective, lacking restricted electronic access and proper audit trail functionality. Additionally, the company failed to verify changes to computer software. Aseptic processing areas exhibited critical deficiencies. Validation for disinfection processes was outdated (last in 2005 or 2007) and lacked justification, and sporicidal agents were not routinely used despite validation studies showing existing disinfectants were ineffective against spores. Procedures to prevent microbiological contamination were inadequate, lacking instructions for sanitization and proper operator behavior, and failing to validate sterilization processes for key equipment components and stoppers using biological indicators. Furthermore, the firm lacked established procedures for inspecting equipment cleanliness before manufacturing operations. Toyobo Co., Ltd is required to respond to these observations with comprehensive corrective and preventive actions to ensure compliance with regulatory standards and safeguard product quality.