Contaminant-Free Synthetic Heparin Under DevelopmentAug 19, 2008 | Parker Waichman LLP
Following over 80 American deaths and hundreds of illnesses attributed to contaminated heparin derived from pig intestines processed in China, chemist Robert J. Linhardt is making the blood-thinner heparin without using animal tissue.
Conventional heparin is often made in small workshops in China, which contributes to contamination, according to Linhardt, who is a professor of chemistry, biology, and chemical engineering at Rensselaer Polytechnic Institute in Troy, New York. "Our group has been working on understanding heparin biosynthesis for almost 30 years," he said. "We are working on what might be the next generation of heparin production, with no animal source." Pig intestines are the traditional manufacturing source for heparin.
Although synthetic heparin has been made in the recent past, it was only manufactured in microscopically small amounts. Linhardt is scheduled to speak Sunday at the American Chemical Society annual meeting, in Philadelphia and described a new method of heparin biosynthesis that has produced amounts measured in milligrams. Linhardt hopes that production can be dramatically increased. The process starts with a polysaccharide, a chain of carbohydrate units, extracted from the bacterium E. coli. "We treat it to reduce the molecular size, then subject it to enzymatic steps to convert it to heparin," he explained. "We use recombinant enzymes that are part of the natural pathway for heparin synthesis." The challenge is in "scaling up the process so it is commercially viable," Linhardt said. "We are now working with one liter amounts. There are million-liter fermenters. We have to scale up three orders of magnitude, which is pretty daunting but not impossible."
Heparin is administered via injection and is used to prevent blood clotting during heart surgery, kidney dialysis, and other procedures. With a fully synthetic form of heparin, the sort of contamination seen this past year would be a thing of the past, Linhardt said. Linhardt’s group received funding from the U.S. National Institutes of Health (NIH). "It's too early to approach a pharmaceutical company," he said. "We have talked to a number of them. They all are interested in the approach but want to wait."
Linhardt said he is aware that there are several drugs designed to replace not only heparin, but also the widely used clot-preventing medication Coumadin. Such medications are in clinical trials in Europe, with some already approved for medical use. "I won't deny there's competition," Linhard said. "But those drugs are a thousand times more expensive than heparin. Also, they are not as good as heparin. It has multiple activities, many of which benefit patients. Those drugs are very specific. They work well only for a small number of applications." Synthetic heparin could cost no more than the animal-derived product, Linhardt said. "We believe that the heparin market is here to stay," he said.
Meanwhile, in March, the Food and Drug Administration (FDA) confirmed it found oversulfated chondroitin sulfate in samples of the active ingredient used in Baxter-supplied heparin. The FDA said the chondroitin sulfate was molecularly changed to mimic heparin’s blood-clotting properties and was supplied to Baxter by Changzhou SPL, a Chinese plant partially owned by Wisconsin-based Scientific Protein Laboratories.