New Data Link Heparin Deaths to Chinese Batches, FDA Says
Tuesday, April 22, 2008
Food and Drug Administration officials said yesterday they have new evidence that links hundreds of serious adverse reactions and scores of deaths among patients given the blood thinner heparin to a man-made contaminant introduced during production in China.
Janet Woodcock, director of the agency's Center for Drug Evaluation and Research, said that the contaminant has been traced to 12 different Chinese companies and has been found in heparin batches shipped to 11 nations, all of it from China.
Chinese officials, however, disputed the finding and said that the compound -- over-sulfated chondroitin sulfate -- could not be "the root cause" of the adverse reactions.
Speaking yesterday at the Chinese Embassy in Washington, Jin Shaohong, a top official with the Chinese National Institute for the Control of Pharmaceutical and Biological Products, said some of the batches of heparin associated with severe allergic reactions and distributed by Baxter International did not have the synthetic chondroitin in them. He also said that heparin with the contaminant has been found in many nations, but that none have reported a similar spike in harmful reactions as in the United States.
Jin said the Chinese government was conducting its own investigation of the heparin issue, which would include a visit today to Baxter's New Jersey processing plant, where officials hoped to collect additional samples of the tainted drug. He said the allergic reactions could have been created by impurities introduced when the imported raw heparin was refined by Scientific Protein Laboratories (SPL) of Wisconsin and then prepared for distribution in New Jersey.
The FDA disputed that claim.
Jin said categorically that "the results of our recent investigation and other available evidence do not support the theory that the root cause" of the adverse reactions to heparin was the over-sulfated chondroitin that the FDA identified as the likely culprit. He said Chinese officials are as eager as their American counterparts to find out what caused the reactions.
FDA officials have raised the possibility that the contaminant was intentionally added to the heparin, but have said they still don't know for sure how it got into the supply chain.
Baxter spokeswoman Erin Gardiner said her company disagreed with the Chinese conclusions, adding that the evidence is now strong that the over-sulfated chondroitin caused the problem. She also said the Chinese were incorrect when they said some batches of heparin that caused severe reactions did not contain chondroitin.
Woodcock said that Chinese officials had tested batches of heparin with methods less sensitive than those used in the United States and elsewhere and had missed the presence of the contaminant.
She said FDA scientists now believe the adverse reactions were most pronounced when large doses of the drug were administered quickly, and the contaminant acted as a "mediator" that caused a response similar to an allergic reaction. Woodcock said the agency planned to make its research public soon so it could be reviewed by other scientists.
Representatives of more than 12 nations, including China, joined the FDA last week in a closed-door meeting on the heparin reactions. They agreed, among other things, to hold an international summit on drug and drug ingredient inspections in 2009, Woodcock said.
Also yesterday, the FDA issued a warning letter to one of the Chinese suppliers of heparin, Changzhou SPL, which is wholly owned by the Wisconsin-based SPL.
"Equipment used to manufacture heparin sodium USP is unsuitable for its intended use," the FDA told the supplier. Agency inspectors, who visited the Chinese facility in late February, also found that the company did not properly evaluate its own suppliers, who provide crude ingredients extracted from pig intestines, and did not have a proper system for removing impurities.
SPL disputed the findings and said the contaminant was not introduced into the heparin in the Changzhou plant but rather was in the raw material, which is purchased from pig farmers and wholesalers in the region.
The Changzhou plant has been supplying heparin for patients in the United States since 2004. The FDA acknowledged last month that it had never inspected the plant because it confused it with another facility with a similar name, and Chinese officials said they did not inspect it because it was listed as a plant producing chemicals rather than pharmaceuticals.
The sharp spike in allergic reactions to heparin from November through February has become emblematic of concerns over the large and growing number of prescription drugs and drug ingredients being imported from lightly regulated nations such as China and India. It has also highlighted the question of whether the FDA has the resources and will to regulate foreign-made drugs with the same intensity as it does American-made products. Numerous members of Congress have called for greater oversight, and the FDA has announced that it will soon open its first office in China.
Reflecting the increasingly political nature of the debate, Sen. Edward M. Kennedy (D-Mass.), chairman of the Senate Health, Education, Labor and Pensions Committee, said in a statement that "Congress and the Administration must work with the FDA to keep Americans safe from these tainted drugs. At a time when the American people are being asked to provide yet more billions for Iraq, we must make certain that the resources are found to address challenges at home."