The story started with reports of unusual numbers of allergic reaction, many serious, to parenteral heparin, a drug in use for over 70 years to reduce blood clotting. Most of the afflicted patients were dialysis patients who get large doses (boluses) of heparin to prevent blood clots during dialysis. The reactions included "nausea, difficulty breathing and rapidly falling blood pressure that can lead to death." The reactions affected patients receiving heparin from multi-use vials made by Baxter International. "About 350 events linked to Baxter's heparin have been reported since the end of last year compared with less than 100 reports in 2007." Baxter recalled lots of heparin which "all came from a Baxter facility in Cherry Hill, N.J."(1)
But then the plot started to thicken. Last week we found out:
- Baxter Actually Didn't Make the Heparin. A Chinese Factory Made It, then Shipped It to a US Company, Which Shipped It to Baxter. "A Baxter spokeswoman confirmed that the company gets the active pharmaceutical ingredient for its heparin from a U.S. supplier that operates a plant in China and another in the U.S., but she declined to identify the supplier." (2)
- The FDA Never Inspected the Factory Which Made the Heparin. "The FDA said last night that it hadn't inspected the Chinese facility that made the active ingredient in the Baxter drug." (2)
- The FDA Admitted It Should Have Inspected the Factory. "The FDA spokeswoman said the plant making the active ingredient 'was supposed to be inspected' but 'our understanding is that, due to human error, and inadequate information technology systems, a pre-approval inspection, which would normally be conducted, was not.'"
- Responsibility for the Manufacture of the Heparin was Dispersed Among Multiple Entities in Two Countries. "Baxter said the active ingredient for its heparin was supplied by Scientific Protein Laboratories LLC, a Waunakee, Wis., company with a manufacturing facility there and a joint-venture operation called Changzhou SPL in Changzhou...." Note that "Changzhou SPL ... [is] also known by its Chinese name, Kaipu Biochemical Co...." Furthermore, "Scientific Protein ... is majority-owned by the Bethesda, Md., buyout firm American Capital Strategies Ltd...." In addition, "the Chinese operation ... is also owned by Changzhou Techpool Pharmaceutical Co., of China."(3)
- Failure of the FDA to Inspect the Chinese Factory Violated the Agency's Own Policies. "The Food and Drug Administration violated its own policies when it approved for sale a crucial blood-thinning drug without first inspecting a Chinese plant which, along with a plant in Wisconsin, made the drug’s active pharmaceutical ingredient."(4)
- The Factory that Made the Heparin Was Not Certified to Produce Pharmaceuticals, and Was Never Inspected by Chinese Regulators Either. "A Chinese factory that supplies much of the active ingredient for a brand of a blood thinner that has been linked to four deaths in the United States is not certified by China’s drug regulators to make pharmaceutical products, according to records and interviews. Because the plant, Changzhou SPL, has no drug certification, China’s drug agency did not inspect it." So, "a spokesman for China’s State Food and Drug Administration, Shen Chen, said Friday that 'as far as we know, it is not a drug manufacturer — it is a producer of chemical ingredients.'" (5)
- Production of Heparin was Relocated So It Could Be "in the Middle of All Those Pigs in China." "SPL moved production to China three years ago, he [David strunce, chief executive of Scientific Protein Laboratoris] said, because the Chinese are the world's dominant supplier of hogs."(6)
OK, to summarize, the heparin that Baxter ships with its logo on it was made by a Chinese chemical factory not licensed to produce pharmaceuticals. The rationale for using a Chinese plant was its proximity to pigs. The factory was never inspected by Chinese or US drug regulators. The Chinese factory shipped the heparin to a US company, which shipped it to Baxter. And now heparin made in this way has been associated with hundreds of allergic reaction, many serious, including 4 fatalities.
This case also made it clear how suspect is the provenance of many drugs sold in the US (and around the world) by formerly respectable pharmaceutical companies. "China is now the world's largest producer of active pharmaceutical ingredients.... In 2005, China had $4.4 billion, or 14% of the world's $31 billion market for active drug ingredients...."(2) But, "the FDA may only inspect around 7% of foreign drug-making facilities in a given year...."(2) "A legal requirement for drug manufacturers to get inspected every two years applies only to domestic plants, not the growing list of overseas facilities."(3) The FDA "inspected foreign drug plants at best once every 13 years. The agency's record in China ... is even worse. Of the 700 approved Chinese drug plants, the agency has been able to inspect only 10 to 20 each year...." (4) It is not clear whether the FDA or its Chinese counterpart has ever inspected a Chinese chemical factory that produced pharmaceuticals without a license. Yet, "an unlicensed chemical plant in China made a tainted drug ingredient that poisoned more than 170 people in Panama, killing at least 115."(5) Furthermore, "the Chinese government does not inspect production plants that make drugs solely for export to the U.S. and other markets."(6) So, "'it's a little bit like the wild, wild west as this relationship with the Chinese continues to grow,' said Kip Kirkpatrick, partner with Chicago-based private-equity firm Water Street Healthcare Partners, which has investments in China's drug and medical-product market."(6)
So this tragic case raises many questions for the leaders of the various organizations involved. Why did Baxter farm out the actual production of a drug which it sold as its own? How hard did Baxter scrutinize the production of the drug? How hard tid SPL scrutinize its production? Did Baxter, SPL and/or the FDA realize the drug was being produced in an unlicensed Chinese chemical factory which had never been inspected by the Chinese or US government? If they did, why did they accept its product? If they didn't, why didn't they know? I presume others will be trying to find out the answers to these questions.
Most US drug companies (as well as many other US health care organizations, for-profit and not-for-profit) now are run by businesspeople, not physicians or scientists. Such businesspeople seem to too often worship at the altar of management gurus. Such gurus seem to preach the need to cut costs by out-sourcing and off-shoring, often without too much concern about how well some factory or country in an exotic location will produce the desired product or service. Obviously, such concerns should be heightened because the attractively low prices of out-sourced products and services could be due to poorly paid and unmotivated, if not exploited workers, and shoddy operations using poor quality equipment and supplies. The leaders of health care organizations ought to be particularly worried that cutting costs by out-sourcing may affect the quality of their products and services, and hence may endanger patients' health and safety. The case of the dangerous heparin suggests that these leaders have not been worried enough. One would think that the health of the patients who ultimately would have heparin injected into them ought to outweigh the proximity of a factory to pigs.
If we don't get people who run health care organizations to put patients before profits, there are going to be more dead and injured patients.
References1. Jepsen B. Baxter halts heparin production after reports of allergic reaction. Chicago Tribune, Feb 11, 2008 (link)
2. Mathews AW, Burton TM. China plant played role in drug tied to 4 deaths. Wall Street Journal, Feb 14, 2008. (link)
3. Burton TM, Mathews AW, Zamiska N, Fairclough G. Heparin probe finds U.S. tie to Chinese plant. Wall Street Journal, Feb 15, 2008. (link)
4. Harris G, Bogdanish W. F.D.A broke its rules by not inspecting Chinese plant with problem drug. New York Times, February 15, 2008. (link)
5. Bogdanich W, Hooker J. China didn't check drug supplier, files show. New York Times, Feb 16, 2008. (link)
6. Greising D, Japsen B. China doesn't check plants that make U.S. drugs. Chicago Tribune, Feb 16, 2008. (link)