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

The FDA inspected Zhejiang Tianyu Pharmaceutical Co., Ltd. from February 28 to March 4, 2022, identifying significant deviations from current Good Manufacturing Practice (CGMP) for active pharmaceutical ingredients (API), rendering their API adulterated.

Key violations include: 1. **Failure to extend investigations:** The firm did not adequately investigate a (b)(4) impurity in (b)(4) API, limiting testing to a fraction of affected lots and failing to include lots manufactured as early as 2017. They also continued to release and distribute API without mitigating controls despite knowing of the impurity risk. 2. **Failure to establish impurity profiles:** The firm failed to systematically evaluate manufacturing processes to identify potential impurities like (b)(4) in (b)(4) API and (b)(4) in (b)(4) starting material, despite customer complaints and external notifications. This led to the release of 39 lots for the U.S. market with unacceptable (b)(4) impurity levels. 3. **Failure to clean equipment at appropriate intervals:** Equipment used in (b)(4) synthesis had visible residues (brownish rust-like and thick black spots) on product contact surfaces, indicating inadequate cleaning. A complaint investigation linked this to out-of-specification (b)(4) impurity in a returned lot. 4. **Repeat deviation - Cleaning validation:** The firm failed to complete cleaning validation studies