China NMPA Inspection - Dujiangyan Zhongshan Pharmaceutical Factory - June 20, 2018

An unannounced inspection by the State Food and Drug Administration of Dujiangyan Zhongshan Pharmaceutical Factory, published June 19, 2018, revealed serious non-compliance with the Good Manufacturing Practice for Pharmaceuticals (2010 Revision) concerning their bear bile powder production. The inspection identified inadequate rectification of prior deficiencies, including critical issues with data integrity. Specifically, the HPLC workstation and freeze dryer control systems lacked essential access controls, and test data was not backed up, allowing unauthorized parameter changes. The company also failed to properly analyze and address previous computer system time modifications impacting stability testing. Furthermore, the factory was found to be producing contrary to approved processes. They changed their drying method from hot air to freeze drying since November 2017 without proper research or regulatory filing. Key quality management system deficiencies included insufficient QA/QC staffing, absent inspection of packaging materials, and key personnel not adequately reviewing batch records, with approval times preceding inspection completion and missing authorized signatures. Significant equipment and layout changes in 2017 were implemented without proper change control procedures. Validation issues were also pervasive, with unconfirmed process parameters, unverified cleaning for critical equipment, and new machinery not confirmed or registered. The company utilized inconsistent raw material feed rates without proper process validation, and cold chain conditions for raw materials were unconfirmed. As a result, the Sichuan Provincial Food and Drug Administration was directed to revoke Dujiangyan Zhongshan Pharmaceutical Factory's GMP certificates and initiate legal proceedings for their violations.