Investigations by the U.S. Food and Drug Administration (FDA) into the potential cause of the hundreds of allergic reactions and 19 deaths linked to Baxter International’s heparin product have revealed the source of the contaminant, a heparinlike substance called oversulfated chondroitin sulfate. It is unclear if the contaminant is directly responsible for the allergic reactions. The allergic reactions have occurred predominantly in patients undergoing kidney dialysis, heart surgery and apheresis (a procedure that removes whole blood to extract a portion of it, such as platelets). Baxter, supplier of 50% of the U.S. heparin market, announced a voluntary recall of nine lots of heparin on January 17, 2008.
Heparin is a generic anticoagulant drug derived from the intestines of pigs. A portion of the active ingredient used to make Baxter’s heparin product comes from suppliers in China, where uneven regulation, plus the employment of some crude and unsanitary heparin processing workshops have triggered greater global scrutiny.
Oversulfated chondroitin sulfate can be chemically altered to “resemble” heparin. Chondroitin sulfate, an inexpensive and readily available substance derived from animal cartilage becomes more like heparin with the addition of extra sulfate. When combined with actual heparin, the substance can be difficult to detect.
The FDA has yet to determine whether the product was intentionally altered. “We cannot rule in or out whether this was accidentally or deliberately introduced into the product,” said Dr. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research.
However, the ease with which chondroitin sulfate can be procured combined with the low processing cost is, for some, ample evidence that manipulation has occurred to create a cheaper alternative to straight heparin manufacturing. “The presence of this contaminant clearly shows a deliberate attempt to increase the yield of heparin,” said Jawed Fareed, PhD, professor of pathology and pharmacology at Loyola University Medical Center near Chicago. He has been studying the heparin batches in question, but cautioned that it is too early to determine whether the adverse reactions were caused by the contaminant.
On March 14, 2008, the FDA announced receiving approval from the U.S. State Department to establish eight full-time, permanent positions at U.S. diplomatic posts in China. The move, pending authorization from the Chinese government, is expected to occur within the next 18 months. The agency also intends to hire a total of five local Chinese nationals to work with the new FDA staff at the U.S. Embassy in Beijing and the U.S. Consulates General in Shanghai and Guangzhou.
In the meantime, the FDA has confirmed that it has more than a dozen of the world’s pre-eminent heparin chemists studying oversulfated chondroitin sulfate and other possible contaminants. Baxter and Scientific Protein Laboratories LLC, the Baxter supplier that produced the contaminated heparin, are both conducting independent inquiries.
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Source: The Wall Street Journal, March 20, 2008