Contaminant In Heparin Is Identified

As in the pet food case, the chondroitin sulfate in the heparin is considerably cheaper to produce than pure heparin.

The tainted drug was distributed by Baxter International, which bought it from a Wisconsin company that gathered and distilled heparin in a plant it built in Changzhou, China. Heparin is made from the intestines of pigs, and chondroitin sulfate can be produced from pig cartilage. Woodcock said the contaminant, over-sulfated chondroitin sulfate, is a chemically modified form of the joint pain supplement that could not be detected by standard quality-control testing.

Baxter's supplier, Scientific Protein Laboratories of Wisconsin, said yesterday in a statement it believed the substance did not come from the Changzhou plant but further upstream in the supply chain, which includes small family farmers and weakly monitored "consolidators."

"Based on what we know, we believe that the contamination identified by the FDA occurred earlier in the supply chain," said Robert Rhoades, an independent consultant with Becker & Associates, who is working with the company.

"Using the very recent tests used by the FDA to detect the contaminant, [the Changzhou plant] tested samples of incoming crude heparin material. The samples showed 'peaks,' indicating that the contaminant was in the material before it reached" the plant, Rhoades said.

Rhoades said a recent increase in allergic reactions to heparin supplied to German patients by a different manufacturer suggests "that the problem is significantly broader than material provided" by the Changzhou plant. The active ingredient for much of the world's heparin comes from China.

Woodcock said because the "over-sulfated" form of the compound detected during testing is not a natural substance, it had to have been deliberately modified. She said some manufacturers have experimented with the over-sulfated form of the supplement, but there have been few clinical trials and there is no approved use for it.

Although the contaminated heparin is the largest and highest-profile instance of tainted prescription drugs made in China, it is not the first. In the late 1990s, a spike in deaths associated with the intravenous antibiotic gentamicin was linked to China-based Long March Pharmaceuticals. Although no definitive link was ever established, tests by German researchers later found a wide range in quality and effectiveness in what were supposed to be uniform dosages of the drug, leading them to write that "it was assumed" the deaths "were related to faulty manufacture."

Hubbard, the former FDA official, said it is not surprising that tainted drugs supplied though agency-approved channels are showing up from abroad. "The history of some of these developing countries in terms of substituting or counterfeiting concerns is a long and well-documented one," he said. "And at this point, the FDA doesn't have the resources or system in place to make sure some of these bad drugs don't get through to the public."