FDA WARNING_LETTER - Kyowa Hakko Kogyo Co., Ltd. - June 25, 2010

The FDA issued a Warning Letter to Kyowa Hakko Kogyo Co., Ltd. (now Kyowa Hakko Bio Co., Ltd.) on September 29, 2010, following a June 21-25, 2010, inspection of their API manufacturing facility in Hofu City, Japan. The inspection revealed significant deviations from Current Good Manufacturing Practice (CGMP), rendering their APIs adulterated under 21 U.S.C. § 351(a)(2)(B). The firm's July 14, 2010, response was deemed insufficient.

Key violations included: 1. **Failure to thoroughly investigate OOS results:** Incomplete documentation and insufficient scope of investigations into high impurity levels and laboratory errors. 2. **Inadequate sampling and test procedures:** Chromatographic methods lacked system suitability tests, and incoming material sampling was scientifically unsound and not performed by the firm. 3. **Unvalidated stability-indicating analytical methods:** The method for testing API stability was not validated to be stability-indicating, with incomplete forced degradation studies. 4. **Improper analytical method validation and modification assessment:** The API assay method lacked essential validation elements, and gradient changes were made without re-validation. 5. **Lack of control system for laboratory records:** Repeat observation from a 2007 inspection; raw data was not recorded in controlled, unique-