FDA WARNING_LETTER - Changzhou SPL Company, Ltd ( a/k/a "Kaipu") - February 26, 2008

This FDA Warning Letter, dated April 21, 2008, was issued to Changzhou SPL Company, Ltd (aka "Kaipu") following an inspection from February 20-26, 2008. The inspection revealed significant deviations from U.S. Current Good Manufacturing Practice (CGMP) in the manufacture of active pharmaceutical ingredients (API), specifically heparin sodium, USP, rendering their API adulterated under section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act.

Key violations include: 1. **Lack of assurance for impurity removal:** The firm lacked adequate evaluation of critical processing steps for impurity removal, and critical process parameters were not well-defined or controlled. An impurity profile for heparin sodium API was not established, and validation studies failed to demonstrate consistent impurity removal. 2. **Inadequate supplier evaluation:** The firm failed to have adequate systems for evaluating suppliers of heparin crude materials, using material from an "unacceptable" vendor in API shipped to the U.S. 3. **Unverified test methods:** USP compendial test methods for heparin sodium USP were not verified for suitability under actual conditions of use, particularly the protein test method, lacking data on suitability, accuracy, and detection limits. 4. **Unsuitable equipment:** Equipment tanks used in the final processing step were observed with adhering unidentified material, scratches, and non-smooth surfaces, indicating