MIT Study Proves Heparin Deaths, Reactions Result of Fake IngredientJun 5, 2008 | Parker Waichman LLP
A group of scientists, led by researchers at the Massachusetts Institute of Technology (MIT), have shown that a counterfeit chemical found in batches of tainted heparin was responsible for hundreds of adverse reactions and 81deaths among patients in the US. The study, published in the current issue of the New England Journal of Medicine, also reports that a new test to detect contaminated heparin has been developed.
In January, Baxter International began recalling heparin injections in the US after some patients experienced extreme - and in some cases fatal - allergic reactions, including difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that was life threatening after being administered the products. In March, the Food & Drug Administration (FDA) confirmed that it had found oversulfated chondroitin sulfate in samples of the active ingredient used in Baxter heparin. The FDA said the chondroitin sulfate was molecularly changed to mimic heparin’s blood-clotting properties. That ingredient was supplied to Baxter by Changzhou SPL, a Chinese plant partially owned by Wisconsin-based Scientific Protein Laboratories LLC.
The FDA has not determined when the chondroitin sulfate entered the heparin supply chain, but suspicion rests on China. Changzhou used two consolidators to supply it with a raw ingredient made from pig intestines, as is chondroitin sulfate. Those consolidators obtained the ingredient from unregulated workshops. In April, FDA Commissioner Andrew von Eschenbach has said that while the FDA has no specific evidence that the chondroitin sulfate contamination was intentional, “the concern is that it had to be by design.” The reason for the counterfeiting may have been economic. According to The New York Times, oversulfated chondroitin sulfate costs $9 a pound compared with $900 a pound for heparin.
While the Chinese have not disputed that the chemical made its way into the heparin at some point along its manufacturing supply chain, regulators there have insisted that the chondroitin sulfate could not have caused the adverse reactions. But the MIT study is strong evidence that such a theory is without merit.
Using lab animals - in this case pigs - the scientists found that chondroitin sulfate activates two inflammatory pathways: one that initiates blood clotting and dilation of the blood vessels, and one that produces anaphylactic toxins. The first leads to a dangerous decrease in blood pressure, the second a serious allergic reaction. In blinded laboratory tests, the contaminated heparin activated the biological pathways, while normal heparin did not.
The experiments also helped scientists come up with a test for detecting the chemical in heparin. Heparin consists of a long, complex chain of repeating sugar molecules. Oversulfated chondroitin sulfate, which is derived from animal cartilage, has a structure very similar to that of heparin and thus cannot be identified with the tests normally used to inspect batches of heparin. Traditional heparin safety screens test only for contaminants such as protein, lipids or DNA, and thus would not detect the presence of sugar chains that do not belong. The MIT research team played a key role in developing new technologies for analyzing complex sugars. Using the new technology, the research team was able to detect the presence of the faulty sugars.