Heparin Contaminant Identified by FDA

The FDA has identified the “heparin-like” contaminant in the active pharmaceutical ingredient (API) of Baxter Healthcare’s (Deerfield, IL) recalled heparin products to be over-sulfated chondroitin sulfate, a commonly available, cheap chemical compound.

Chondroitin sulfate is a dietary supplement that is commonly used for the treatment for osteoarthritis. The over-sulfated chondroitin sulfate compound, however, is an experimental compound that is not approved for use in the US. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, said in a March 19, 2008, media conference call that chondroitin sulfate is a biologically derived compound that is commonly available, but over-sulfated chondroitin sulfate is chemically modified and not found in nature. “The over-sulfated chondroitin sulfate, unlike common chondroitin sulfate, mimics heparin’s activities, and therefore appears to be heparin when subjected to standard tests,” she explained. The contaminant was identified after testing was done in collaboration with several laboratories. The FDA has not yet made a link between the contaminant and the adverse reactions that were reported in patients who received bolus doses of Baxter’s heparin products.

Woodcock had previously announced that the “heparin-like” substance that the FDA had identified in the API was found in concentrations making up 5 to 20% of the APIs that were tested. She said that the substance reacted in a way that was similar to heparin, which is why it was not detected earlier. Out of the 28 samples tested from the Changzhou plant, 20 were contaminated with the heparin-like compound.

In a March 14 conference call, Woodcock announced that the FDA put a border alert into effect for all heparin products manufactured by the Changzhou SPL (Changzhou, China) plant, Baxter Healthcare’s (Deerfield, IL) supplier of heparin API.
The FDA has received reports of 46 deaths of people who have used heparin products, and 785 adverse reactions to heparin products. They have confirmed that 19 of the deaths and 350 of the severe reactions are related to the drug.

The API for Baxter’s recalled heparin products are produced by Scientific Protein Laboratories’ (SPL, Waunakee, WI) manufacturing sites in Wisconsin and Changzhou, China. On February 29, 2008, Baxter recalled multi-dose vials, single-dose vials, and HEP-LOCK heparin flush products, which all contain the API that is produced by the Changzhou SPL plant.
On March 6, 2008, German authorities initiated a precautionary recall of heparin products after receiving reports of adverse reactions that were similar to those reported to the FDA.

For more information on the heparin situation, see BioPharm’s previous news coverage.

FDA Issues Border Alert for All Heparin Products

German Ministry of Health Recalls Heparin Products

FDA Finds "Heparin-like" Contaminant in Heparin API

Baxter Expands Heparin Recall, FDA Issues 483 to China Facility

Letters Sent to Baxter and FDA Request Answers on Heparin Situation