FDA 483 - Shanghai Henlius Biologics Co., Ltd. Songjiang Site 2 - March 11, 2025

On March 11, 2025, the U.S. Food and Drug Administration (FDA) issued a Form 483 to Shanghai Henlius Biologics Co., Ltd. Songjiang Site 2, following an inspection conducted from February 24 to March 11, 2025. The inspection revealed significant concerns regarding the company's manufacturing processes for drug products, particularly aseptic operations. Key observations included a failure to establish adequate process controls to ensure product quality and sterility. Investigators observed inadequate cleaning of filling lines, evidenced by visible particles and fibers, and a deficient cleaning standard operating procedure. There was also a lack of sufficient control to prevent particle introduction into drug products, with atypical particles found and a high defect rate in one filling line. Further issues noted were the absence of unilateral airflow protection for open products, inadequate air flow visualization studies, and less sensitive HEPA filter integrity testing methods. The FDA also highlighted a lack of assurance in consistent aseptic filling, citing multiple instances of equipment malfunctions that aborted media fills and production batches. Procedures designed to prevent microbiological contamination were found to be insufficient, with observations such as sanitized equipment exposure to less controlled environments, improper handling of critical equipment, and inadequate media simulation. Finally, the Quality Unit's oversight was deemed inadequate, particularly concerning visual inspection processes, pressure differential monitoring, and a failure to implement corrective actions for past leakage events. The company is required to promptly address these observations by implementing comprehensive corrective and preventive actions to ensure compliance with good manufacturing practices.