FDA 483 - Changzhou SPL Company, Ltd - February 26, 2008

On February 20, 21, 22, 25, and 26, 2008, the FDA inspected Changzhou SPL Company, Ltd, an API (animal origin) manufacturer located at 3 Changhong West Road, Wujin, Changzhou City, Jiangsu Province, China. The inspection, led by Investigator Regina T. Brown and Chemist Zi-Qiang Gu, resulted in a Form 483 issued to General Manager Mr. Van-wang on February 28, 2008.

The inspection revealed eight observations regarding the manufacturing of Heparin Sodium USP: 1. Critical processing steps for Heparin Sodium USP were not identified, and the evaluation of impurity removal (proteins, nucleotides, viruses, endotoxin, bacteria, heavy metals) at appropriate steps was not performed. Annual test results were unavailable. 2. Improvements from raw material testing approval, process parameter changes, and an added step, as per the 1/05 process validation report, were not demonstrated. 3. No impurity profile was established for Heparin Sodium USP, and degradants were not evaluated during stability testing. 4. Manufacturing instructions for Heparin Sodium USP were incomplete, lacking descriptions of manual manipulations, actual manually entered temperatures and times, and recorded operator observations (e.g., level measurements). 5. Test method verification for USP methods (Nitrogen Determination, Protein, Total Aerobic Microbial Count) used