FDA Says Contaminant in Blood Thinner Is Nearly Identified

Tests of the active ingredient produced in China to make heparin for Baxter International found a contaminant in 20 of 28 samples, further tying a spike in serious and occasionally fatal allergic reactions in American patients to the drug's overseas sources, officials said yesterday.

Food and Drug Administration officials also said they are close to identifying the "heparin-like" contaminant found in some of the heparin causing allergic reactions. They said that once they know exactly what the contaminant is, they will probably know whether it was deliberately added or unintentionally produced during manufacturing.

The finding that potentially significant amounts of Chinese-produced heparin ingredients were contaminated led the FDA to demand rigorous new testing of all imported heparin ingredients and products. They said most manufacturers had agreed to begin the more sophisticated tests themselves, but some will have their products tested by the FDA.

Janet Woodcock, the new chief of the FDA's Center for Drug Evaluation and Research, said the testing is part of a formal "import alert" and will improve monitoring of the drug. "We will get a much better picture of whether there's any contaminant existing, and we can trace it back" to its sources, she said.

Partly in response to the heparin findings, the FDA announced last night plans to place eight full-time regulators at U.S. diplomatic posts in China, pending approval from the Chinese government. The agency called it "a significant step toward ensuring access to safe food, drugs and medical devices in the global market."

A broad international investigation is under way into hundreds of allergic reactions linked to Baxter International's heparin injections, which are used as a blood thinner during surgery and for dialysis patients.

The inquiry has led to China, where Baxter's main supplier -- a plant owned by Scientific Protein Laboratories (SPL) of Wisconsin -- is located. China is now the world's primary source of the active ingredient in heparin, which is made from the intestines of pigs.

Much of the supply comes from small, family-run workshops near slaughterhouses, which send their raw ingredients to larger "consolidators" before they reach plants such as the one owned by SPL in Changzhou, outside of Shanghai. FDA officials said they generally do not inspect small producers and consolidators but have been talking with Chinese officials about what local inspectors might do.

Another brand of heparin from a different Chinese supplier has been recalled in Germany after 80 patients there got sick. As a precautionary measure, Japan has begun using the sophisticated new test developed by Baxter and the FDA to test all heparin products coming into that country.

The drug has been on the market since the 1930s and is used by millions of Americans annually. While isolated allergic reactions to heparin have been detected before, Baxter and the FDA became concerned in December when the number of allergic reactions jumped. By the time the Baxter product was recalled, more than 700 adverse reactions had been reported.

The FDA has said that as many as 21 deaths were associated with the drug, but Baxter said in a statement yesterday that none of the deaths is confirmed and only four are clearly associated with the company's product. Agency officials said they would soon make their count of heparin-linked deaths more definitive.

Woodcock said that while they have not yet established a direct link between the contaminated heparin and the allergic reactions, there is now "a guilt by association." She said the heparin-like molecule found in the contaminated lots was similar to the drug itself and was not detected until the new refined tests were developed. FDA chemists are "close to nailing down exactly what it is," she said.