As a result, FDA to require testing of all imported heparin
FRIDAY, March 14 (HealthDay News) -- The contaminant found in the blood-thinner heparin, which has been linked to hundreds of allergic reactions and possibly 19 deaths in the United States, has been traced to a Chinese plant that processed raw ingredients for the drug, U.S. health officials said Friday.
As a result, the U.S. Food and Drug Administration said it will start testing all heparin products to be imported into the United States. The announcement comes as the agency continues its investigation into the contamination with heparin produced by Baxter Healthcare Corp., of Deerfield, Ill.
The heparin was supplied to Baxter by Scientific Protein Laboratories of Waunakee, Wisc., and its Changzhou SPL plant in Changzhou City, China. The company is Baxter's main supplier of the active pharmaceutical ingredient in heparin.
"The active pharmaceutical ingredient comes from the Changzhou SPL plant in China," Dr. Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research, said during an afternoon teleconference.
"The FDA conducted an inspection in this plant, and we obtained 28 samples of the active pharmaceutical ingredient," Woodcock said. "We found 20 of these samples had a heparin-like contaminant."
In light of the finding, the FDA has placed the Changzhou SPL plant on "import alert," Woodcock said, meaning the plant has agreed not to export any more heparin to the United States.
In a statement released late Friday, Baxter said its staffers "have been working seven days a week since late December 2007" trying to determine the nature of the contaminant. The company has so far ruled out a number of infectious pathogens, dioxins or the pufferfish toxin (tetrodoxin).
"While Baxter's analysis is not complete, the company has evidence that the unknown material is a highly sulfated glucosaminoglycan-like (GAG-like) material," the company said. "While heparin-like, the material is structurally different from naturally-occurring heparin. The unknown material has approximately the same molecular weight as heparin and is similar in other ways, which is why standard testing would not detect its presence."
In the meantime, all other heparin destined for the United States from abroad must be tested for the contaminant by the manufacturers of the drug, the FDA's Woodcock said. Five manufacturers have agreed to such testing. Any manufacturers that don't agree to test will have their products withheld by the FDA for testing by the agency, she said.
These five manufacturers that have agreed to the testing make up a "substantial" portion of the heparin supply in the United States, Woodcock said. "Manufacturers making this test commitment will be able to import the active product ingredient from overseas sources without delay to avoid shortages in supply of heparin, which would also be a very dangerous situation for patients," she said.
Heparin is a blood thinner often given to dialysis patients and people undergoing heart surgery. The raw materials for the drug come from the mucous lining of pig intestines. Many of those pigs come from rural farms in China, with the intestines often processed by unregulated mom-and-pop workshops before further processing at Scientific Protein's plant in Changzhou.
The FDA hadn't uncovered a direct link between the contaminant and the adverse reactions and deaths. "We know that some of the suspect batches of heparin that were causing the adverse events have this contaminant in it. So there is an association between the contaminant in the presence of adverse events, but it is not a direct causal link yet," Woodcock said at a March 5 press conference.
Since the end of December, there have been 785 reports of allergic reactions associated with Baxter's heparin product. This compares with less than 100 reports of adverse reactions in all of 2007.
There also have been 46 deaths among heparin users, 19 possibly linked to the drug and four more conclusively so, according to the FDA.
Adverse reactions included difficulty breathing, nausea or vomiting, excessive sweating and falling blood pressure, which can lead to life-threatening shock.
A German company that recalled its heparin products last week found that some batches contained the same heparin-like contaminant in China, the Wall Street Journal reported Friday.
Rotexmedica GmbH tested its recalled heparin and found that ingredients purchased from the Chinese company Yantai Dongcheng Biochemicals were contaminated, Olaf Schagon, head of quality management at Rotexmedica, told the Journal.
Contaminated products from China have been an ongoing worry for the FDA. If the heparin contamination turns out to be deliberate, it would be reminiscent of last year's scandal when a Chinese company was charged with adding the toxic chemical melamine to an ingredient used in U.S. pet food that killed thousands of dogs and cats. The melamine let the ingredient pass chemical inspections for protein content, the Associated Press reported.
For more on heparin, visit the U.S. National Library of Medicine.
SOURCE: March 14, 2008, teleconference with Janet Woodcock, M.D., director, Center for Drug Evaluation and Research, U.S. Food and Drug Administration; March 14, 2008, statement, Baxter Healthcare Corp.
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