The US Food and Drug Administration (FDA) has identified the structure and source of the contaminant found in lots of heparin.
The contaminant, which has been linked to severe allergic reactions and deaths, was found in crude lots of heparin at a Chinese processing plant. The substance has been identified as over-sulfated chondroitin sulfate.
Researchers initially had difficulty identifying the contaminant because it is so similar to heparin. Over-sulfated chondroitin sulfate has approximately the same molecular weight as heparin, and both materials belong to the class of molecules known as glucosaminoglycans (GAGs).
It is still unknown whether the over-sulfated chondroitin sulfate was a byproduct of the heparin production process or if it was intentionally added to the active pharmaceutical ingredient.
After learning about the source of the over-sulfated chondroitin sulfate, the FDA issued a border alert that requires all finished heparin, as well as heparin source material, to be tested before it is allowed into the US. Five heparin manufacturers, companies that supply most of the heparin used in this country, have agreed to conduct the tests.
Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said the agency would test heparin products made by companies that cannot conduct the testing themselves. Any product that is not tested or fails the tests will be destroyed.
Scientific Protein Laboratories is the company that supplied crude heparin from the Changzhou plant in China to the biopharmaceutical company Baxter. Scientific Protein Laboratories has said it is cooperating with the FDA, and the Changzhou plant is not currently producing heparin.
In addition to the new testing instituted at the US borders, the FDA said heparin testing is now being conducted worldwide. Germany and Japan are among the countries that have started testing.
Germany recalled heparin last week after a cluster of about 100 serious allergic reactions, including hypotension and anaphylaxis. Japan has also recalled heparin but has not reported any adverse events linked to heparin injections.
Both Scientific Protein Laboratories and Baxter have conducted massive voluntary recalls of heparin products. Since Baxter recalled all of its heparin vials, there have been no additional deaths.
Last week, the FDA received 785 reports of adverse events associated with heparin. Those reports included 46 deaths, but Dr Woodcock said only 19 were related to the allergic profile associated with the Baxter heparin.
Baxter has said it cannot confirm that heparin has caused any fatalities as a result of an allergic reaction. The company said there are 4 cases in which patients received Baxter heparin and suffered an allergic-type reaction to the drug.
Baxter also said there is not yet enough medical data available to draw a firm conclusion that the reaction caused death. In each of these cases, the patient had multiple underlying complex medical conditions. Three of the 4 patients had undergone, or were in the process of undergoing, invasive cardiac surgery.
The heparin saga began January 17 of this year, when Baxter recalled the first batch of heparin after receiving reports of the allergic reactions. Recalls of the drug have continued since that time.
The FDA released the news of the contaminant’s source March 14 and the discovery of its structure March 19.
