The Wall Street Journal-20080214-China Plant Played Role In Drug Tied To 4 Deaths

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China Plant Played Role In Drug Tied To 4 Deaths

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A Chinese facility that hasn't been inspected by the U.S. Food and Drug Administration made the active ingredient in much of the widely used Baxter International Inc. blood-thinner that is under investigation after reports of hundreds of allergic reactions and four deaths among the drug's users, the agency said yesterday.

The disclosure is likely to add to broad concerns about the safety and quality of products imported from China and elsewhere in the developing world. A tide of tainted goods ranging from pet food to children's toys has prompted recalls and increased scrutiny of Chinese-made wares around the world.

Although it isn't known whether the Chinese plant played a part in the drug's problems, its role as a supplier to Baxter is expected to fuel questions about U.S. regulators' ability to ensure the safety and quality of imported drugs and drug ingredients.

On Monday, Baxter announced that it had temporarily halted production of its version of the generic anticlotting drug heparin because of about 350 bad reactions potentially tied to the drug, including four fatalities, primarily in patients undergoing kidney dialysis and heart surgery.

Yesterday, both Baxter and the FDA said it wasn't clear that the ingredient from the Chinese supplier was tied to the bad reactions. "We honestly don't know" the cause, an FDA spokeswoman said.

China is now the world's largest producer of active pharmaceutical ingredients -- the chemical compounds needed to make finished pills and other drugs. In 2005, China had $4.4 billion, or 14%, of the world's $31 billion market for active drug ingredients, according to a report last year from Credit Suisse.

Recent testimony from the Government Accountability Office said that the FDA may only inspect around 7% of foreign drug-making facilities in a given year, and it would take the agency more than 13 years at that rate to inspect all the plants. The testimony also said the FDA "cannot provide the exact number of foreign establishments that have never been inspected."

The agency also had varying counts of how many overseas facilities ship drug ingredients to the U.S.

"American lives will remain at risk until the FDA commits the resources necessary to inspect imported drugs and drug ingredients," said Bart Stupak, the Michigan Democrat who heads the House Energy and Commerce Subcommittee on Oversight and Investigations, in a statement yesterday.

The FDA said last night that it hadn't inspected the Chinese facility that made the active ingredient in the Baxter drug. "While no FDA inspection of the facility has been conducted to date, preparations are being made to perform an inspection as soon as possible. We have already requested expedited access to the facility, facilitated through a recently signed agreement with the Chinese State Food and Drug Administration. FDA also has requested the facility's inspectional data and adverse event reports connected to the product," an agency spokeswoman said in an emailed statement.

The FDA spokeswoman said the plant making the active ingredient "was supposed to be inspected" but "our understanding is that, due to human error, and inadequate information technology systems, a pre-approval inspection, which would normally be conducted, was not." The spokeswoman couldn't immediately provide the name or location of the Chinese supplier.

The agency has inspected a facility in Cherry Hill, N.J., she said, where the finished version of the drug is packaged by a Baxter subsidiary.

A major competitor of Baxter's, APP Pharmaceuticals Inc., of Schaumburg, Ill., also gets the active ingredient for much of its heparin from a Chinese supplier. "We have not experienced" any adverse reactions like those potentially connected to the Baxter drug, a spokeswoman for APP said.

An FDA official estimated that around 40% of the adverse reactions among patients taking the Baxter drug were classified as serious. They ranged from stomach pain to vomiting and diarrhea, low blood pressure, speeding heartbeats and fainting.

Heparin, which is derived from pig intestines, has been sold in the U.S. since the 1930s. Baxter had been selling the product at a rate of about 100,000 vials a day. Given either intravenously or by injection, the drug is used in a wide range of medical procedures to treat or prevent clotting.

In particular, the drug is essential during procedures like cardiac surgery, in which a patient's blood is removed from the body. It is also used in kidney dialysis and in apheresis, a procedure used to treat some immune-system disorders, in which blood is taken outside the patient's body and some components are removed.

A Baxter spokeswoman confirmed that the company gets the active pharmaceutical ingredient for its heparin from a U.S. supplier that operates a plant in China and another in the U.S., but she declined to identify the supplier. She said that Baxter, in cooperation with the FDA, plans to inspect the Chinese factory, but she declined to say when. The company spokeswoman said Baxter has been working with the U.S. supplier for 20 years, and the supplier has made the heparin ingredient for three decades. Baxter has only sold heparin since late 2002, when it acquired a unit of Wyeth that marketed the drug, she said.

"There have not been changes" recently in the Chinese operation, the Baxter spokeswoman said. She added, "It's not a foregone conclusion" that the Chinese facility is connected to the problem.

Because heparin is widely used in hospitals and dialysis centers, Baxter didn't suspend sales of existing supplies of the drug, in order to avoid shortages. Officials of the FDA made that decision along with executives of the Deerfield, Ill.-based company.

Baxter supplies about 50% of the heparin used in the U.S., so the possibility of a shortage arising is a real one. Although more than a week ago the company said it had concluded the reactions were confined to nine lots of heparin, it later found the adverse reactions had spread beyond those lots and to a wider range of dosages.

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Nicholas Zamiska contributed to this article.