On January 9, CDC investigators notified the FDA, which sent investigators to inspect Baxter's manufacturing plant in Cherry Hill, N.J., where they found contaminated doses of blood thinners containing heparin. Baxter then voluntarily recalled nine lots of heparin—about 10 percent of the company's annual production of the blood thinner—and the FDA warned health care providers to stop administering the drug.
U.S. health care facilities had been purchasing more than one million multiple-dose vials of heparin-based blood thinners monthly, half of which were made by Baxter. Most of the remaining heparin products used in the U.S. are distributed by American Health Packaging in Valley Forge, Pa; APP Pharmaceuticals, LLC, in Schaumburg, Ill.; B. Braun Medical, Inc., in Bethlehem, Pa.; Covidien (formerly Tyco Healthcare) in Mansfield, Mass.; Hospira, Inc., in Lake Forest, Ill.; and Medtronic, Inc. [[http://www.reuters.com/article/healthNews/idUSN0730155620080507]], in Minneapolis. American Health Packaging, B. Braun, Covidien and Medtronic recalled heparin-based products from March through May due to concerns that they might be contaminated. Baxter was the hardest hit: Physicians reported about 350 adverse events from Baxter's heparin products in January and February alone, compared with fewer than 100 reports in all of 2007, according to the FDA. APP increased its production capacity and has taken over as the major supplier of the U.S. market.
Most of the problems involved dialysis patients who had received high intravenous doses of a type of heparin (high molecular weight heparin) that thins the blood for about an hour while they are undergoing treatment. Another type—low molecular weight heparin—thins the blood for hours longer than the high molecular weight variety and is more likely to be used on patients staying in the hospital (to prevent clots while bedridden). There are some synthetic forms of low molecular weight heparin, such as sanofi–aventis's Lovenox, but currently there is no synthetic high molecular weight alternative on the market.
Baxter had called Linhardt to tap his expertise and to help track down the source of contamination. He agreed to share his findings with FDA officials, who soon began calling him for daily updates and to get his take on what they found. "Often the FDA suggested experiments that I should try in my lab," he says. "Apparently, the FDA was using my lab to confirm and validate results that other laboratories were reporting."
On the trail of a killer
Within weeks, the FDA—working with Linhardt as well as research teams at the Massachusetts Institute of Technology (M.I.T.) and Washington University in St. Louis—had narrowed the list of suspected contaminants to oversulfated chondroitin sulfate (OSCS), because it mimics heparin's capabilities and appears to be heparin when tested in the lab. Although OSCS is based on chondroitin sulfate (prepared from animal cartilage or beef trachea) that many people take as an anti-inflammatory to treat osteoarthritis, OSCS has the opposite effect, activating immune system enzymes that cause inflammation as well as a drastic drops in blood pressure. The question: What was it doing in batches of heparin, where it would have no purpose other than to increase the volume, driving up sales of an artificially pumped up product, Linhardt says.