Akeso Biopharma Co., Ltd. – FDA 483, Aug 7, 2023

Akeso Biopharma Co., Ltd. received an FDA Form 483 following an inspection conducted from July 25 to August 7, 2023, at their drug substance and drug product manufacturing facility in Zhongshan, China. The inspection revealed significant deviations from Current Good Manufacturing Practices (cGMP), indicating a lack of robust quality control and process integrity.Key issues identified include inadequate validation of manufacturing processes, particularly for a specific drug substance and the labeling/packaging of drug product. The company demonstrated insufficient controls over working cell banks and failed to adequately address recurring process variability, leading to production disruptions. Furthermore, observed aseptic processing deficiencies, such as unsterilized equipment, improper handling, and inadequate environmental monitoring, raise concerns about the sterility assurance of drug products.The FDA noted that procedures to prevent microbiological contamination were not consistently followed, and smoke studies were not fully representative of actual operations. Control strategies for adventitious agents and cross-contamination in the multi-product facility were found to be deficient, including the use of potentially inferior testing methods and "restricted release" of materials without complete testing. Investigations into deviations, such as HEPA filter failures and microbial excursions, lacked thoroughness, consistent microbial identification, and adequate assessment of product quality impact, including stability and potential microbial metabolites.Additionally, the quality unit's oversight was deemed inadequate, with concerns regarding data integrity (shared access, unreviewed audit trails), acceptance of critical components without periodic validation, and unscientific risk assessments. Discrepancies between manufacturing processes and regulatory filings were also cited, along with poorly defined or unfollowed standard operating procedures, particularly concerning alarm responses and environmental monitoring. Akeso Biopharma is required to provide a comprehensive response detailing corrective and preventive actions to address these serious observations and ensure cGMP compliance.