March 24 — /WASHINGTON/ — Investigators have moved closer to understanding how a widely used blood thinner killed as many as 19 Americans, identifying the chemical that tainted the heparin products. Meanwhile, the American companies that made heparin and its main ingredient blamed suppliers from China for the contamination.
The Food and Drug Administration states that the chemical was a kind of souped-up version of a compound commonly used to treat arthritic joints. The chemical — over-sulfated chondroitin sulfate — is not approved for use in prescription drugs sold in the United States, and it doesn’t normally figure in the production of heparin, FDA officials say.
“It should not be in heparin and, obviously, it should not be in the form that it is in,” Dr. Janet Woodcock, director of FDA’s drug division said in a conference call with reporters.
Now that they’ve identified the substance, investigators are trying to determine whether it caused the more than 700 reports of serious side effects in heparin users, and whether it was introduced deliberately into heparin products.
As much as half of the main ingredient in suspect heparin supplies was found to be the contaminant. That chemical looks like the main ingredient in heparin and acts like it during routine quality testing. It was made by chemically treating the compound normally used to treat joint pain, FDA officials say.
That compound — chondroitin sulfate — is structurally similar to heparin and shares some of the same blood-thinning properties, but is not used for that purpose, says Stuart T. Haines, a professor at the University of Maryland School of Pharmacy who specializes in the proper use of drugs. The chemical is often made from shark, squid, and other fish, Haines says.
Heparin’s main ingredient usually comes from pig intestines that are crushed and then purified. China is the world’s leading supplier. The ingredient is shipped to the United States for processing into finished heparin products.
Although they won’t go so far as to place blame on heparin suppliers in China, FDA officials say they’re working with Chinese authorities on determining how the contaminant got into shipments. They said additional supplies from the Changzhou, China, plant that supplied the main ingredient to the recalled heparin products were found to have the contaminant.
Scientific Protein Laboratories, which partly owns the Changzhou plant and sold the main ingredient used in the recalled heparin products, says contamination occurred somewhere along its chain of Chinese suppliers. The Waunakee, WI, company issued a press release saying its testing showed that the raw materials it received were tainted.
The company is recalling all of its heparin ingredients made from materials provided by Chinese suppliers whose goods tested positive for the contaminant.
Baxter International Inc. of Deerfield, IL, recalled most of its heparin products last month after some were linked to hundreds of reports of serious side effects, including quickening heartbeats, nausea, and dizziness. Baxter issued its own statement that also attributed the contamination to Chinese suppliers.
The recall has triggered a worldwide investigation and deepened concerns about the safety and quality of imports from China. Senator Edward M. Kennedy of Massachusetts called on FDA to get from drug companies the names of their suppliers now that the contaminant has been identified.