FDA 483 - Boehringer Ingelheim BioPharmaceuticals (China) Ltd. - July 09, 2023

An FDA inspection conducted from May 29 to June 9, 2023, at Boehringer Ingelheim BioPharmaceuticals (China) Ltd., a manufacturer of drug substances and products, identified significant deficiencies in compliance with manufacturing regulations. Key observations included a failure by the quality unit to ensure full release of drug substance lots before further processing. Issues were also noted in visual inspection procedures for injectable products, specifically regarding statistically sound sampling for Acceptance Quality Limit (AQL) testing. The inspection found inadequate controls to prevent microbiological contamination during sterile product manufacturing, with sterilized components exposed, operators making direct contact with sterile surfaces, and deficiencies in environmental monitoring and equipment validation. Significant concerns were raised about data integrity, including insufficient access controls for computerized systems, lack of raw data backup for in-process equipment, and inadequate assurance of data completeness and accuracy. The firm also failed to properly investigate discrepancies and out-of-specification results, and laboratory testing procedures for critical assays were found to be inadequate, potentially leading to inaccurate results. Furthermore, open drug substance manufacturing operations were conducted in an insufficiently controlled environment, increasing contamination risk. The company is required to address these observations by implementing comprehensive corrective actions and providing a detailed response to the FDA.