Perfline |  |
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Baxter International Co had to recall several lots of porcine heparin because of a possibly related increased incidence of mortality and morbidity among patients treated with the drug.
The manufacturer and the FDA identified this heparin as "contaminated" by an unidentified substance in a proportion of 20%.
The chinese plant that manufactures the gross product and sells to Baxter has no explanation for the contamination. The Wall Street Journal reports that the Shenzhen Hepalink plant (China) has been inspected and approved nine times in recent years by government health authorities, including the U.S. Food and Drug Administration, China's drug watchdog and German regulators. Buyers have done their own audits 25 times. To track a process that starts with crude heparin extracted from pig intestines, the company keeps more than 300 pages of data for each batch to "ensure traceability of each lot," Shenzhen Hepalink Chairman Li says.
To date there has been about 20 deaths and 800 severe reactions reported to the FDA in the USA and another unknown number of similar occurrences in German.
As China has grown to be the larger manufacturer of pharmaceutical products, it is possible that other countries have also imported heparin from the same manufacturer.
A few years ago, bovine heparin was abandoned because of risks of transmission of a spongiform encephalytis.
We should be aware of these happenings and double check the heparin we administer to our patients.
March 10, 2008 07:55 pm - Rio de Janeiro, Brazil. |
Theofilo Gauze | |
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Heart Surgery has long being hunted by phenomena like that. Many times we've seen patients that would otherwise fare well and for some unclear reason die in the PO setting. In those cases ussualy the surgeon get's the blame all alone because so many people and drugs are involved that there's no other target to a clear shot. Fortunately new info is bringing light over these problems and hopefully saving lives. March 12, 2008 10:41 am - Brasil |
Vladimir Aronsky | |
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This is hardly a phenomena. The heparin was made using no control whatsoever. The only control that is performed is that there is a daily dose that is given to a single sheep to see if the product works. China has been chosen for low cost and abundance of pigs, it takes 3,000! pigs to make 1 kg of heparin. The animals are not screened for any disease, which was the primary reason why we no longer make heparin from bovine lungs (mad cow). Hopefully we will be able to synthesize heparin in a lab soon, see article: http://www.physorg.com/news109600112.html
V
ladimir Aronsky, CCP.
March 13, 2008 11:39 pm - Long Island, NY. |
Rick Wheaton, CCP | |
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According to an article in the Los Angeles Times, March 20, 2008, the contaminant in heparin has been identified as chondroitin sulfate. This food supplement is made from animal cartiladge, and, according to the article, “On a molecular level, it is related to heparin.” The article states that the chondroitin , which is cheaper to produce than heparin, may have been substituted somewhere along the line to increase the profits of middlemen, or it could have occurred through “a mishap or some kind of misguided experiment.” The level of the contaminant ranged from 2% to 50% in lots of heparin tested by the FDA. And according to a statement by FDA Deputy Commissioner Janet Woodcock, hypersulfated chondroitin sulfate was "not an approved drug in the United States, nor should it be present in heparin."
The article continues: “The FDA and the heparin manufacturer, Baxter Healthcare Corp., said sophisticated testing identified the contaminant as hypersulfated chondroitin sulfate.
Illinois-based Baxter said it believed the contaminant was introduced into the supply chain before raw heparin reached its supplier, Scientific Protein Laboratories. The Wisconsin-based supplier is a joint-venture partner in the Changzhou, China, facility that supplied the tainted heparin to Baxter.
Both companies think the contamination occurred before the heparin reached the Changzhou plant. That facility is supplied by three "consolidators" who process raw material from other suppliers, including slaughterhouses.
FDA officials stopped short of calling it a case of pharmaceutical counterfeiting, although such scams are on the rise worldwide.
"We cannot rule whether this is accidentally or deliberately added," Woodcock said. "We are 99% sure it is not a natural component."
March 29, 2008 09:01 pm - California |
Perfusion Line | |
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Heparin Contamination Was Deliberate Act to Cut Costs?
This note was reported by Sue Hughes in Heartwire (WebMed).
April 30, 2008 – Contamination of the worldwide heparin supply, which resulted in a substantial increase in adverse events and an estimated 81 deaths in the US, appears to have been a deliberate act to increase profits in Chinese workshops.
Speaking at a Congressional hearing on the debacle held on April 29, 2008, David Nelson, an investigator for the Committee on Energy and Commerce, noted that the contaminant, oversulfated chondroitin sulfate, was apparently added to crude heparin in China at some stage in the production process by parties that have yet to be identified. "This contaminant has anticoagulant properties that mimic heparin, but at a much lower production cost--about $20/kg vs $2000/kg to produce crude heparin. Accordingly, there is speculation that the contaminant was added deliberately to increase profits for the workshops and/or consolidators that ship the crude material to Changzhou SPL, SPL Wisconsin, and other heparin [active pharmaceutical ingredient] API producers," he reported.
May 2, 2008 10:34 pm |
Andres Pérez | |
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There has been described about 80 lethalities related to the use of "contaminated" heparin in the United States. An investigation made by Bayer representatives and FDA authorities revealed that the product has been distributed only to a few countries. There is no information, up to this moment, regarding fatal complications of the altered heparin around the world, except for a few cases ocurred in Germany. May 4, 2008 10:46 am - Mexico |
James Turtle | |
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A few studies have identified the contaminant found in heparin: oversulfated chondroitin sulfate (OSCS)—and the mechanism by which it is believed to bring about adverse events.
At a press conference earlier this week, Dr Janet Woodcock (director of the FDA's Center for Drug Evaluation and Research) said: "This solid mechanistic link between OSCS and the type of adverse reactions seen strengthens considerably the hypothesis that this contaminant is responsible," although regulators from China, where the contaminant has been traced to, have said they are not convinced that OSCS is the cause of the adverse events.
Two published papers are written by two teams of scientists, both of which are led by Dr Ram Sasisekharan (Massachusetts Institute of Technology, Cambridge, MA). In one paper, published online April 23, 2008 in Nature Biotechnology, more details of the chemical structure of the oversulfated chondroitin sulfate contaminant are reported, and tests that can be used to detect it are described.
The other paper, published online on the same day in the New England Journal of Medicine (NEJM), describes the mechanism by which OSCS could induce the type of adverse reactions seen with heparin, which have included hypotension, facial swelling, tachycardia, urticaria, and nausea.
The authors of the NEJM paper report that OSCS can directly activate the contact system, and in laboratory studies, it induced generation of C3a and C5a—potent anaphylatoxins derived from complement proteins. In addition, they say that OSCS directly activates the kinin-kallikrein pathway in human plasma, which can lead to the generation of bradykinin, a potent vasoactive mediator. They further note that OSCS can induce a profound hypotensive response in pigs, which the authors say provides "a potential biologic link between the contaminant and the anaphylactic reactions seen in affected patients."
(Extracted from a paper in The Heart.org)
May 6, 2008 09:31 pm - England |
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