Baxter Healthcare Corporation temporarily halted manufacture of the anticoagulant heparin in response to more than 400 reported incidents of severe allergic reactions and abnormally low blood pressure (hypotension). The U.S. Food and Drug Administration (FDA) announced Baxter’s decision on February 11, 2008. Four deaths have already been linked to use of the drug. Heparin, which is derived from the intestines of pigs, is administered to patients intravenously to prevent life-threatening blood clots in the veins, arteries and lungs. The generic drug, marketed in the U.S. since the 1930s, is commonly used in hospitals and dialysis centers.
The allergic reactions have occurred predominantly in patients undergoing kidney dialysis, heart surgery and apheresis procedures (removal of whole blood to extract a portion of it, such as platelets). They include difficulty breathing, chest pain, excessive sweating, diarrhea, throat swelling, nausea and vomiting. Hypotension is associated with dizziness, fainting and in some cases, life-threatening shock.
Baxter, supplier of 50% of the U.S. heparin market, first announced a voluntary recall of nine lots of heparin on January 17, 2008, as the number of patients reporting adverse reactions began to rise. The pharmaceutical company is currently conducting an investigation to determine the actual cause. While it has suspended production of multi-dose heparin vials, Baxter continues to distribute previously manufactured product, based on an agreement with the FDA
The FDA has inspected the Baxter manufacturing facility in Cherry Hill, NJ, and the plant of a Baxter supplier, Scientific Protein Laboratories LLC in Waunakee, WI. The agency is also inspecting Changzhou SPL, a second Scientific Protein plant located in Changzhou City, China, which had been supplying a significant amount of the active ingredient in Baxter’s heparin.
Meanwhile, the FDA has come under strong criticism for not fully vetting these plants. It had not inspected Changzhou SPL’s plant prior to approval because the agency mistook Changzhou SPL for another Chinese plant with a similar name. The FDA’s failure to inspect the Chinese enterprise has drawn pointed questions from several legislators. U.S. Representative Bart Stupak (D-MI), chairman of a House investigative subcommittee, and U.S. Senator Charles E. Grassley (R-IA) sent letters to the FDA on February 14, 2008, requesting more information concerning inspections of plants manufacturing heparin.
Baxter spokesperson Erin Gardner said the company inspected Changzhou SPL less than six months ago and the Waunakee plant within the past year. She said that Baxter had found slight chemical differences in the lots that Scientific Protein sent. She added, “but it is unclear what impact the differences would have” on the companies’ heparin product.
The quality of product from Changzhou SPL may have been further compromised by two additional factors. The plant was never certified by China’s own drug agency and therefore, never inspected by Chinese regulators. Secondly, due to a shortfall in healthy pig stocks, heparin suppliers were increasingly turning to crude, unregulated and, in some instances, unsanitary heparin processing workshops.
“We provided crude heparin to Changzhou SPL,” said Chen Jianjun, a sales manager with supplier Nantong Koulong. He added that some of Koulong’s stock comes from the unregulated workshops.
The Wall Street Journal reported on February 19, 2008, that another manufacturer of heparin is now increasing its production to fill the void. Several large hospitals have already switched to Schaumburg, IL-based APP Pharmaceuticals to supply their heparin.
To date, Baxter and the FDA have not determined the source of the heparin problems. Investigations are ongoing.
Sources: The New York Times, February 15, 16 and 28; The Wall Street Journal, February 12 and 19; and The Washington Post, February 19