NEWS OF THE W EEK
CAUSE OF HEPARIN WOES UNCLEAR PHARMACEUTICALS: Hunt for source of adverse reactions to blood thinner examines FDA, China roles
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Heparin is often used in patients undergoing kidney dialysis.
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DA AND BAXTER HEALTHCARE are searching, so far fruitlessly, for the cause of about 350 adverse reactions to Baxter’s heparin drug, a blood thinner used, for example, by patients undergoing kidney dialysis. Four patients have died after receiving heparin. Under scrutiny as possible contributors to the heparin problem are Baxter, its Chinese drug ingredient supplier, and FDA itself. Meanwhile, supplies of the critical anticoagulant could be in jeopardy. Last week, FDA officials said agency inspectors were on their way to Changzhou SPL, a Chinese facility owned by Scientific Protein Laboratories, a Wisconsin-based firm that has been Baxter’s main active ingredient supplier. Earlier, FDA started investigations at facilities run by Baxter in Cherry Hill, N.J., and by SPL in Waunakee, Wis., to find the source of the problem. The Changzhou plant was never evaluated the way it should have been as a supplier of materials to the U.S.,
acknowledged Joseph Famulare, deputy director of FDA’s Office of Compliance, during a conference call last week. “The wrong firm was put into the FDA database, and therefore [Changzhou SPL] was not evaluated or scheduled for inspection,” he explained. Instead, a firm with a similar-sounding name was looked at by FDA’s compliance office; this firm had recently been inspected and found in compliance, so no further action was taken. China’s State FDA did not inspect the Changzhou plant because it makes export products only. The lapse in oversight is particularly embarrassing for FDA since it has been under fire for its spotty record in conducting foreign inspections (C&EN, Nov. 26, 2007, page 38). “The problem was discovered within the past month,” Famulare added. “To date, this is an isolated situation.” Meanwhile, FDA and Baxter are acting to protect public health. On Feb. 11, FDA issued an advisory to increase awareness of serious events that occurred in patients, particularly those receiving bolus, or largequantity, injections of Baxter’s heparin. The events include severe allergic or hypersensitivity-type reactions. Baxter, which supplies about half of the heparin sold in the U.S., has temporarily suspended production. In use for nearly 70 years, heparin is isolated from animal organ tissues, generally from pigs. It is a complex glycosaminoglycan with a heterogeneous chemical composition and is thus difficult to synthesize. Researchers have been working on chemical or enzymatic synthetic routes, and low-molecular-weight heparins are available but may have different therapeutic effects. Because the medical consequences of a shortage would be serious, FDA and Baxter have not issued a total recall, but chose instead to issue cautions around its use. Meanwhile, FDA is working with other manufacturers, including APP Pharmaceuticals of Schaumburg, Ill., to increase production. APP, which also supplies about half the U.S. market, uses multiple active ingredient providers, including one in China that Famulare says has passed FDA inspection.—ANN THAYER
GOVERNMENT National Research Council urges phaseout of radiation devices Elimination of some 5,000 radionuclide radiation devices, used for a host of medical, research, and industrial purposes in the U.S., was recommended last week by a National Research Council panel. In a report ordered by Congress because of terrorism concerns, the panel recommended the phaseout begin with equipment that uses high-activity cesium-137 in the form of radioactive cesium chloride. The cesium salt is easily dispersible in dirty bombs and is watersoluble, panel members noted, adding that some 1,300 such devices are in use
in the U.S., primarily for blood irradiation and research. With a half-life of 30 years, these cesium chloride devices are reaching the end of their useful lives, warned Leonard W. Connell, a panel member and staff member at Sandia National Laboratories. He also noted that the U.S. currently does not yet have an ultimate national disposal facility or repository for radioactive waste. “We think it is possible to get rid of most of the 5,000 high-activity radiation devices over the next 10 to 20 years if
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there was a national policy to encourage it,” says Theodore L. Phillips, panel chair and professor of radiation oncology at the University of California, San Francisco. “There are replacements” for such devices, he stressed, adding that “some are not practical or economically attractive today, but most are improving and could be so in time.” For cesium chloride, an energetic gamma emitter, Phillips urged replacement with non-radionuclide, mechanical X-ray generators, or less hazardous forms of radioactive materials.—JEFF JOHNSON
