Baxter Healthcare Corporation, which provides half the supply of heparin in the United States, recalled multidose vials of heparin sodium last month after four deaths and 350 reports of adverse events, 40% of which were serious.
More than one million multidose vials are sold each month in the US, and half of them are produced by Baxter, the US Food and Drug Administration said. The source of the heparin, which is made from pig intestines, was imported from China. The FDA said it had not inspected the Chinese plant that produced it.
The initial recall of heparin last month involved nine lots of multidose vials. Since then, Baxter has received reports of adverse reactions with other lots, the company said. Baxter and the FDA are investigating the problem.
A report in the New York Times said that a manufacturing facility in China, Changzhou SPL, which produced the ingredient for heparin, does not have a Chinese drug licence, although it has not been accused of providing a harmful product (www.nytimes.com, 16 Feb, “China didn’t check drug supplier, files show”). The article said that the plant has no drug certification, so the Chinese drug agency did not inspect it, and the FDA said it had not inspected the plant either, “a violation of its own policy.”
Attempts to reach Changzhou SPL were directed to Scientific Protein Laboratories in Waunakee, Wisconsin. As the BMJ went to press the company had not returned the BMJ’s telephone calls. Scientific Protein’s website says that Changzhou SPL is one of its manufacturing sites. The website states, “Heparin Sodium USP, produced at this site, was approved by the FDA in 2004 under a US NDA [new drug application] for import and use in the United States.”
On Monday the FDA said it had not inspected the Changzhou plant that produced the heparin ingredient because it confused the name with that of a similar plant it had already inspected, the Washington Post has reported (www.washingtonpost.com, 19 Feb, “ FDA says it approved the wrong drug plant”). It was now sending inspectors to China to inspect the right plant.
The commissioner of the FDA, Andrew von Eschenbach, should resign, said Bart Stupak, a Michigan Democrat who heads the energy and commerce oversight and investigations subcommittee in the House of Representatives. He and John Dingell, the Michigan Democrat who chairs the parent committee on energy and commerce, wrote a letter to Dr von Eschenbach (available at http://energycommerce.house.gov) criticising “the disastrous state of your agency’s foreign inspection program related to pharmaceuticals manufactured abroad.”
The Chinese plant supplied the ingredient for heparin production to Scientific Protein Laboratories. The company says that it “is regularly inspected by multiple regulatory agencies such as the FDA and USDA [US Department of Agriculture] . . . We maintain a stellar regulatory inspection record.” It sold the heparin supplies to Baxter, says an article in the Milwaukee Journal-Sentinel (www.jsonline.com, 16 Feb, “FDA to inspect Chinese facility”). The article said that the FDA will also inspect Baxter’s plant in New Jersey, which makes the finished form of the drug.
The cause of the adverse events is unknown, the FDA said. They occurred in December and January and were seen mostly in patients undergoing dialysis, cardiac surgery, photopheresis, and plasmapheresis and in some patients with blood clots in arteries or veins. The adverse events included “serious allergic-type hypersensitivity reactions and cases of serious hypotension in association with the use of intravenous bolus doses of heparin sodium for injection manufactured by Baxter,” the FDA said.
To reduce the risk of shortages the FDA is allowing Baxter to continue distributing heparin but recommends that healthcare personnel “avoid bolus dosing with Baxter heparin whenever possible and [use] strategies that may limit the occurrence or severity of adverse reactions if the use of heparin is medically necessary and Baxter heparin is the only heparin product available.”