FDA WARNING_LETTER - Yuki Gosei Kogyo Co., Ltd. - July 21, 2010

This FDA Warning Letter, dated December 9, 2010, addresses Yuki Gosei Kogyo Co., Ltd. following a July 16-21, 2010 inspection of their API manufacturing facility in Fukushima, Japan. The inspection revealed significant deviations from CGMP for API manufacture, rendering their APIs adulterated under 21 U.S.C. § 351(a)(2)(B). The firm's August 6, 2010 response was deemed insufficient.

Key violations include: 1. **Lack of Analytical Method Validation:** Release test methods for aerobic microbial count and endotoxin content of (b)(4) API, intended for parenteral use, were not validated. The firm committed to validation, but FDA requires validation prior to shipping APIs to the U.S. 2. **Unvalidated and Non-Stability Indicating Methods:** The "Purity of (b)(4) by HPLC" method, used for release and stability, was not validated or shown to be stability indicating, failing to detect/quantify impurities/degradants. The system suitability assessment was also inadequate. The firm committed to validation and revising procedures. 3. **Inadequate Instrument Qualification/Calibration:** Analytical instruments and test equipment, such as the GC oven and water bath, were not adequately qualified or calibrated for their intended operating ranges.

General concerns include the firm's failure to adhere