FDA 483 - Shire Human Genetic Therapies, Inc. - March 23, 2022

During an inspection conducted from March 17 to March 23, 2022, the U.S. Food and Drug Administration (FDA) identified significant deviations from good manufacturing practices at Takeda's (Dyax Corp, Shire Human Genetics Therapies Inc.) drug substance manufacturing facility in Lexington, MA. The inspection resulted in four observations detailed in an FDA Form 483, indicating concerns under the Federal Food, Drug and Cosmetic Act regarding drug product quality and safety.

Key issues included inadequacies in manufacturing batch records, specifically regarding the documentation and control of critical process parameters such as viral inactivation times and pump settings for final product filling. One batch record failed to ensure a critical process parameter was not exceeded, and another omitted documentation of a critical integrity check. Furthermore, an observed incident during drug substance sampling showed a technician failing to immediately sanitize hands after dropping and retrieving equipment in a cleanroom, raising concerns about aseptic technique. Control over equipment was also cited, as a laminar flow clean bench's operational specification for its gauge reading was inconsistent with its certification. Lastly, the qualification of compressed gas utilities was found to be inadequate, lacking specific testing for certain contaminants. Takeda is required to respond to these observations with comprehensive corrective actions to ensure compliance.