BEIJING - U.S. FDA last week issued a sharply higher estimate on the number of deaths that have occurred in patients who suffered allergic reactions to the blood thinner heparin.

In a report posted on its Web site, FDA revised upwards to 62 from 19 the estimated number of people who died from allergic or hypotensive symptoms after heparin administration between Jan. 1, 2007 and March 31, 2008 (PharmAsia News, April 10, 2008). The data include heparin produced by any manufacturer, FDA said.

The agency indicated that extreme adverse reactions to the drug, which is used during surgery and dialysis, peaked between December and February; in 2006, it added, only three deaths were reported among people who initially suffered some allergic reaction to heparin.

The FDA cautioned, "The fact that allergic symptoms or hypotension was reported does not mean that these were the cause of death in all cases."

Parallel investigations launched by FDA and Baxter International, one of the leading suppliers of heparin in the U.S., have indicated that most patients who died were administered heparin provided by Baxter, which two months ago expanded its recall to all remaining single- and multi-dose vials in the U.S. (Also see "Baxter’s Chinese API Supplier Cited For “Objectionable Practices;” Remaining Heparin Vials Recalled" - Scrip, 29 February, 2008.).

Testing by FDA and Baxter has shown that the American company's heparin, whose raw components were imported from China, contained a contaminant that might have triggered the allergic reactions and deaths across the U.S.

Baxter spokesperson Erin Gardiner said in an interview with PharmAsia News that since the sudden rise in deaths of patients administered Baxter's heparin, the company has been conducting an investigation into how the contaminant was introduced into the heparin. New nuclear magnetic resonance spectroscopy tests developed by Baxter and FDA have identified the contaminant as hypersulfated chondroitin sulfate, which has the same molecular weight as heparin and shares other chemical similarities with the blood-thinning pharmaceutical (Also see "Chinese Contaminant Was Inexpensive Heparin Mimic – U.S. FDA" - Scrip, 19 March, 2008.).

Gardiner said the contaminant has appeared in not only API supplied to Baxter by Scientific Protein Laboratories, but also in crude heparin produced at SPL's subsidiary in China, which indicates that the substance suspected of causing the adverse reactions originated in Chinese workshops or among Chinese consolidators that supplied Scientific Protein, Baxter says.

"As part of our investigation, we are continuing to seek access to these workshops and consolidators," Gardiner said. But to date the Chinese suppliers of the crude heparin components have not agreed to provide access to Baxter investigators, she added.

Gardiner told PharmAsia News that the company has not yet started searching for an alternative source of raw heparin and has no immediate plans to reintroduce the drug into the U.S. market. She said that Baxter's top priority now is finding "the root cause" of the adverse reactions triggered by its heparin.

China's State FDA recently said in a report that it has been cooperating with U.S. FDA in tracing the origins of heparin contaminants. SFDA said March 28 that tests of crude heparin from the SPL subsidiary in Changzhou using the nuclear resonance technology have similarly detected hypersulfated chondroitin sulfate.

SFDA said that specialists are continuing an investigation, and that results would be made public soon.

In the wake of the heparin scare, FDA recently unveiled plans to set up offices staffed with inspectors in three American diplomatic outposts in China over the next year and a half (Also see "U.S. FDA Move “Beyond Our Borders” Begins With China" - Scrip, 6 March, 2008.).

Du Wen-min, vice director of the Shanghai Center for Adverse Reaction Monitoring, under the city's FDA, told PharmAsia News he welcomes closer cooperation with U.S. FDA. In an interview, Du said that his center "has an extensive database on patient records and pharmacology that might be used in monitoring adverse reactions to drugs in joint operations with the FDA in the future."

- Kevin Holden Platt (pharmasia@elsevier.com)

U.S. FDA Triples Estimate On Deaths Following Allergic Reaction To Blood Thinner Heparin

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