The Baxter heparin scandal has again raised questions over the regulation of overseas drug manufacturers. Last week it was learned that the Food & Drug Administration (FDA) never inspected the Chinese plant that manufactured Baxter International’s heparin. Now it seem that China’s own drug agency never bother to check up on the Baxter heparin supplier either. The Changzhou SPL factory, a major supplier of heparin to Baxter, is not certified by China’s drug regulators to manufacture pharmaceuticals. The Baxter heparin supplier inhabits a regulatory loophole in which chemical companies can export pharmaceuticals without a Chinese drug license. The US majority owner of Changzhou SPL —Scientific Protein Laboratories—also owns a Wisconsin plant that produces the active ingredient in heparin for Baxter. Baxter’s heparin has been linked to four deaths and hundreds more illnesses in the US.
Heparin is a blood thinner administered in surgery and other critical care areas to prevent blood clots, is crucial in dialysis and heart surgery, and is used for the bedridden. Other drugs thin blood, but their effects are not considered as effective. Heparin is administered to millions of patients yearly, and Baxter manufactures about half of all multiple-dose heparin vials sold in the U.S. The FDA reported that, since the end of 2007, it received about 350 reports of health problems associated with Baxter’s multiple-dose injectable heparin; 40 percent were deemed serious. Reactions included difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that—in some—led to life-threatening shock.
In December, American and Chinese regulators signed an agreement under which China promised to begin registering its thousands of companies selling drug ingredients, some of which are the source of counterfeit or diluted drugs. The revelations regarding the Baxter heparin supplier are frightening, given that China provides a growing number of the active pharmaceutical ingredients used in drugs sold in the US. Chinese regulators claim all producers are required to obtain certification by the State Food and Drug Administration; however, some active ingredients in Chinese exports are manufactured by chemical companies not falling under jurisdiction of their drug agency.
Scientific Protein said its Chinese plant had no license from the Chinese agency, but its raw ingredients come from a licensed supplier and that an “independent private U.S. validation company” found the plant to be in compliance with good manufacturing practices. Eric S. Langer, managing partner of BioPlan Associates, which prepares and publishes reports on the biopharmaceutical and biotechnology industry said, “Being able to produce a pharmaceutical or a biologic in the U.S. or anywhere without having regulatory oversight really doesn’t happen. I find it surprising from a regulatory perspective and I find it surprising from a business perspective.”
Karen Riley, spokeswoman for the FDA, said inspectors would be visiting the Changzhou plant soon, but could not be more specific. Erin Gardiner, a Baxter spokeswoman, said while the cause of the adverse reactions is unknown, tests performed by Baxter detected unspecified differences between some lots. She did not say whether the lots came from China or Wisconsin.
Congress criticized the FDA’s oversight of bulk pharmaceutical ingredients made by foreign manufacturers and sold in the US. A growing number of those ingredients now come from China and of 700 approved Chinese drug plants, yet the FDA inspects no more than 20 annually. Two Congressional committees have asked the FDA for more information about inspections of plants making the active ingredient of heparin.