China Orders New Oversight of Heparin, With Tainted Batches Tied to U.S. Deaths

SHANGHAI — health club China’s top drug safety agency has ordered its local bureaus to increase supervision over the production of heparin, a blood-thinning drug that has been linked to at least 19 deaths and hundreds of allergic reactions in the United States, China’s state-run news agency reported Friday.

The drug agency, the State Food and Drug Administration, said producers of the active ingredient in heparin must now obtain their raw material from registered suppliers, and it ordered the suppliers to strengthen their checks on the quality and safety of those raw ingredients.

The announcement, just hours after American officials said they had identified a contaminant in heparin from China, represents a turnabout for Chinese drug regulators. Previously, they had said they did not have oversight of large parts of the industry, and they had called on importing countries to take responsibility for ensuring heparin’s safety. China is the world’s largest supplier of the active ingredient in heparin.

With the drug agency’s announcement, and a related order from the Ministry of Commerce, the government is seeking to bring closer regulation to the heparin industry. Yet officials did not say precisely how they planned to do that, given that so much of the complex supply chain is now unregulated, from thousands of small workshops that gather the raw material from pig intestines up to chemical companies that produce the pure active ingredient in heparin.

The American company that manufactured the finished drug associated with the problems in the United States, Baxter International, has recalled virtually all its heparin products. This week, the United States Food and Drug Administration reported that active ingredients from Baxter’s Chinese supplier, Changzhou SPL, were contaminated with a cheap, unapproved ingredient modified to mimic heparin.

Investigators are still trying to determine whether the contamination was the result of counterfeiting, and whether the fake material health club— oversulfated chondroitin sulfate — was the cause of the allergic reactions.

In a statement on Friday, the American company that controls Changzhou SPL, Scientific Protein Laboratories, said tests had indicated that the contaminant was already in the crude heparin when it reached the Changzhou SPL factory. “We believe that the contamination identified by the F.D.A. occurred earlier in the supply chain,” the company said.

Changzhou SPL, in turn, buys its crude heparin from two wholesalers, called consolidators, that gather it from smaller producers. Last month, The New York Times reported that at least one of Changzhou SPL’s consolidators had received supplies from small unregulated family workshops.

The heparin recall in the United States expanded Friday when B. Braun Medical recalled 23 lots of infusion bags made with an active ingredient that came from Changzhou SPL. The recall came after the heparin-like contaminant was found in one lot of heparin sold to B. Braun. The infusion bags are used by hospitalized patients who need heparin over an extended period, said Karen Riley, a spokeswoman for the F.D.A. B. Braun said no adverse effects had been reported.

Ms. Riley said that because other companies made the infusion bags there should be no shortage of the product.

In recent weeks, the F.D.A. has ordered all American imports of heparin to be inspected for contaminants. Germany has also ordered a recall of some heparin from a different supplier in China after reports of about 80 allergic reactions. That heparin has been found to be tainted as well, but whether the contaminant is the same is not yet known.

The Chinese agency’s order, issued Thursday, was accompanied by a separate announcement from the Commerce Ministry health club. The ministry said it had issued an urgent notice to government offices and trade organizations involved in health and drug exports to step up supervision and inspection of heparin production and to create a system that would allow the industry to trace the path of heparin supplies back to the raw ingredient suppliers.

Much of China’s production of raw heparin begins in homes and tiny factories, where teams of three to five people transform pig intestines into a dry substance that is eventually sold to major pharmaceutical companies.

Most of the small factories are unlicensed and unregulated. They sell to traders and consolidators, who sell the raw heparin to companies like SPL that purify it to produce the active ingredients. Many of them are not regulated by the Chinese drug agency, since they are considered chemical companies, not drug makers.

The active ingredients, in turn, health club are sold to pharmaceutical companies like Baxter that produce the finished drug.