Article - March 8, 2008 - New York Times

Germans Seek China Tie to Blood Thinner Heparin

By Carter Dougherty and Elizabeth Rosenthal

FRANKFURT — The German authorities said Friday that they had asked all German producers of the blood thinner heparin to check whether their ingredients came from China, after allergic reactions to the drug there were linked to two Chinese suppliers.

In cases where China did supply the raw ingredient, manufacturers were asked to test for any irregularities. The German authorities recalled the suspect heparin on Wednesday after receiving reports of allergic reactions in about 80 patients.

Heparin manufactured with Chinese ingredients has been linked to 19 deaths in the United States. Federal drug regulators there said sophisticated tests had found what might be a counterfeit ingredient in the heparin associated with the deaths and serious allergic reactions in more than 700 patients.

That unknown substance mimics real heparin and was found in concentrations of up to 20 percent in some of the suspect drug, according to the United States Food and Drug Administration. But the agency said it had not yet established whether the contaminant was responsible for the allergic reactions.

The suspect heparin in the United States was made by Baxter International, with ingredients from a Chinese company called Changzhou SPL. The discovery that the ingredients for the German-made heparin came from two different Chinese plants has led investigators to suspect that the problem may lie farther back in the supply chain.

The German authorities identified the two plants as Changzhou Quianhong Bio Pharma Company, and the Yantai Dongcheng Biochemicals Company. Both are among the top 10 Chinese exporters of heparin, according to a report last September by the China Chamber of Commerce for the Import and Export of Medicines and Health Products. Officials in the sales departments of both Chinese companies said Friday that they were unaware of the problems in Germany.

The suspect heparin was manufactured by Rotexmedica, a subsidiary of the French company Groupe Panpharma. Rotexmedica, based in Trittau in northern Germany, said Friday that it would not comment on the recall because its executives were busy consulting with regulators. Rotexmedica has issued a worldwide recall for its heparin-containing products, which are mostly exported from Germany, said Ulrich Hagemann, an official in the pharmaceutical safety department of the Federal Institute for Drugs and Medical Devices.

The European Medicines Agency, which is based in Britain, has looked through databases in Europe and concluded that there had been no allergic reactions to heparin in any European countries except Germany.

He said the reactions in Germany were far less severe than those in the United States, and had been traced to three specific batches of heparin produced by Rotexmedica. Those batches as well as other batches containing raw materials from the same sources were recalled March 5, and there have been no other patient reactions since.

Heparin is an injectable blood thinner given to prevent and treat blood clots. It is also used in kidney dialysis and open heart surgery. Adverse reactions have included lowered blood pressure, shortness of breath and an elevated heart rate.

Full story