FDA 483 - Hybio Pharmaceutical Co., Ltd. (Pingshan Factory) - August 08, 2023

From July 31 to August 8, 2023, the FDA conducted an inspection at Hybio Pharmaceutical Co., Ltd.’s Pingshan Factory in Shenzhen, China, a sterile drug manufacturer. The inspection resulted in an FDA 483 observation document, highlighting critical issues in their manufacturing processes. The primary violations centered on the absence of established, written, or followed procedures to prevent microbiological contamination in sterile drug products. Specifically, the sterility testing program during manufacturing process validations was found insufficient, and aseptic manufacturing equipment setup required excessive manual manipulations due to a lack of optimization and post-installation sterilization steps for connections. Investigators also observed poor aseptic techniques by operators, who disrupted critical 'first air' over open components, and noted improper storage of tools within the Grade A RABS that obstructed airflow. Additionally, procedures for equipment cleaning and maintenance were deemed deficient, lacking specific instructions for sanitizing complex parts within the Grade A RABS, rendering some areas inaccessible for effective cleaning. These observations indicate potential risks of product contamination under the Federal Food, Drug and Cosmetic Act. Hybio Pharmaceutical Co., Ltd. is required to thoroughly investigate these findings, develop and implement comprehensive corrective and preventive actions, and submit a detailed response to ensure compliance with good manufacturing practices and safeguard drug product sterility.