A Chinese factory that supplies much of the active ingredient for a brand of a blood thinner that has been linked to four deaths in the United States is not certified by China’s drug regulators to make pharmaceutical products, according to records and interviews.
Because the plant, Changzhou SPL, has no drug certification, China’s drug agency did not inspect it. The United States Food and Drug Administration said this week that it had not inspected the plant either — a violation of its own policy — before allowing the company to become a major supplier of the blood thinner, heparin, to Baxter International in the United States.
Baxter announced Monday that it was suspending sales of its multidose vials of heparin after 4 patients died and 350 suffered complications. Why the heparin caused these problems — and whether the active ingredient in the drug, derived from pig intestines, was responsible — has not been determined.
The plant in Changzhou, west of Shanghai, appears to fall into the type of regulatory void that American and Chinese health officials are trying to close — in which chemical companies export pharmaceutical ingredients without a Chinese drug license.
China provides a growing proportion of the active pharmaceutical ingredients used in drugs sold in the United States. And Chinese drug regulators have said that all producers of those ingredients are required to obtain certification by the State Food and Drug Administration. However, some of the active ingredients that China exports are made by chemical companies, which do not fall under the Chinese drug agency’s jurisdiction.
In December, American and Chinese regulators signed an agreement under which China promised to begin registering at least some of the thousands of chemical companies that sell drug ingredients. Some of these companies are the source of counterfeit or diluted drugs, including those used to treat malaria.
Discussions that led to the accord began after an unlicensed chemical plant in China made a tainted drug ingredient that poisoned more than 170 people in Panama, killing at least 115.
The heparin plant in China has not been accused of providing a harmful product. The American majority owner of that plant, Scientific Protein Laboratories, also owns a plant in Wisconsin that produces the active ingredient in heparin for Baxter.
In response to questions, Scientific Protein issued a statement confirming that its Chinese plant had no license from the Chinese agency, but said that its raw ingredients come from a licensed supplier.
The statement added that an “independent private U.S. validation company” had found the plant to be in compliance with good manufacturing practices. And a spokeswoman for Baxter, which buys heparin’s active ingredient from Scientific Protein, said it had inspected the China plant less than six months ago.
A spokesman for China’s State Food and Drug Administration, Shen Chen, said Friday that “as far as we know, it is not a drug manufacturer — it is a producer of chemical ingredients.”
Eric S. Langer, managing partner of BioPlan Associates, which prepares and publishes reports on the biopharmaceutical and biotechnology industry, said he found it hard to believe that a company exporting the heparin ingredient would not be licensed by Chinese drug regulators.
“Being able to produce a pharmaceutical or a biologic in the U.S. or anywhere without having regulatory oversight really doesn’t happen,” Mr. Langer said, adding, “I find it surprising from a regulatory perspective, and I find it surprising from a business perspective.”
Karen Riley, a spokeswoman for the United States Food and Drug Administration, said inspectors from that agency would be visiting the Changzhou plant soon. Ms. Riley said she could not be more specific. Earlier in the week she described her agency’s failure to inspect the plant as a “glitch.”
Congress has criticized the oversight by the Food and Drug Administration of bulk pharmaceutical ingredients made by foreign manufacturers and sold in the United States. A growing number of those ingredients now come from China. Of the 700 approved Chinese drug plants, the United States agency has inspected only 10 to 20 each year.
Baxter makes roughly half of the United States supply of heparin, which is used widely for surgical and dialysis patients. Problems with Baxter’s heparin were first noticed late last year when four children undergoing dialysis in Missouri had severe allergic reactions minutes after being injected with the drug.
The F.D.A. then allowed Baxter to deliver heparin that it was in the midst of shipping, for fear that a total recall would lead to a shortage of the drug, but cautioned doctors to use as little of it as possible and to administer it very slowly.
The agency also suggested that doctors give steroids or antihistamines with the Baxter heparin to help prevent allergic reactions.
Erin Gardiner, a spokeswoman for Baxter, defended Scientific Protein, saying it had been making the heparin ingredient for more than 30 years. “They have been a good supplier,” she said.
Although the cause of the adverse reactions has yet to be determined, she said tests performed by her company had detected unspecified differences between some lots of the ingredient. She did not say whether the lots had come from China or from the Wisconsin plant, which Scientific Protein also owns.
Those differences had not turned up in routine testing that the company does on active ingredients, Ms. Gardiner said, but she said Baxter had used “advanced testing techniques” to find the differences. She added that it was unclear whether the finding was significant.
Two Congressional committees have asked the Food and Drug Administration for more information about inspections of plants making the active ingredient of heparin.