FDA 483 - Zhejiang Tianyu Pharmaceutical Co. Ltd. - March 04, 2022

During an FDA inspection from February 28 to March 4, 2022, Zhejiang Tianyu Pharmaceutical Co. Ltd., an API manufacturer, received a Form 483 outlining significant deviations from current Good Manufacturing Practices. The observations centered on critical deficiencies within the firm's quality system and facilities/equipment maintenance. Specifically, the company failed to extend investigations to all potentially impacted batches after discovering an out-of-specification impurity in their (b)(4) API, which led to customer complaints and product returns. Their impurity evaluation procedures were also found inadequate, not thoroughly assessing potential by-products during process development and failing to identify key impurities, leading to distributed non-conforming batches. Furthermore, equipment cleaning and maintenance practices were insufficient. The firm released material without completing cleaning validation, demonstrated inconsistent adherence to cleaning schedules, and FDA investigators observed rust-like and black spots on product-contact surfaces of synthesis equipment. An existing maintenance procedure also lacked instructions for addressing rust. These issues indicate a lack of control over potential contamination risks. Zhejiang Tianyu Pharmaceutical Co. Ltd. is required to implement comprehensive corrective and preventive actions to rectify these serious quality and maintenance deficiencies.