FDA WARNING_LETTER - Yunnan Hande Bio-Tech. Co. Ltd. - May 21, 2010

The FDA issued a Warning Letter to Yunnan Hande Bio-Tech Co., Ltd. following a May 17-21, 2010 inspection of their API manufacturing facility in Kunming, China. The inspection revealed significant Current Good Manufacturing Practice (CGMP) deviations, rendering their APIs adulterated. The firm's June 2, 2010 response was deemed insufficient.

Key violations include: 1. **Inadequate Complaint Investigations:** Failure to thoroughly investigate out-of-specification complaints (e.g., optical rotation for lot (b)(4)) and extend investigations to other affected batches. Optical rotation testing was not conducted under required temperature conditions (USP <781> specifies 25°C ± 0.5°C, not 20°C), and temperature correction factors were not applied. The firm's Certificate of Analysis (COA) for (b)(4) API falsely claimed USP compliance. This was a repeat observation from a 2004 inspection. 2. **Deficient Reprocessing Procedures:** Lack of adequate procedures and stability data for reprocessing API batches, including the use of reserved, retained, and expired samples, without demonstrating that the quality of new batches is unaffected throughout their shelf life. 3. **Inadequate QC Instrument Calibration:** Failure to have a robust performance qualification program for QC laboratory instruments (e.g., HPLC, analytical balances, Karl Fisher syringe), lacking