China’s heparin revisited: What went wrong and has anything changed?
DOI:
https://doi.org/10.5912/jcb579Keywords:
crude, heparin, adulteration, China, manufacturing, supply chain,Abstract
China is the world’s largest producer of crude heparin. In 2007, tainted Chinese crude heparin made its way into the global finished heparin supply chain killing 149 persons in 11 different countries including 81 deaths in the US. While China never formally admitted that it was the source of the tainted heparin, US and European regulatory officials determined that adulterated crude heparin was intentionally introduced (for economic gain) into the Chinese heparin supply and subsequently shipped to other countries for final pharmaceutical formulation. After China was implicated as the source, tainted heparin disappeared from the global heparin supply chain. This paper reviews the social and economic factors that were likely responsible for the Chinese incident and whether or not another economically-motivated case of crude heparin adulteration is possible in China.
References
Cox, M.N.D., Lehninger, Principles of Biochemistry, ed. Freeman. 2004.
Linhardt, R.J., Heparin: An Important Drug Enters Its Seventh Decade. Chemistry & Industry, 1991. 2: 2-5.
Usdin, S., The Heparin Story, in Biocentury. 2009, BioCentury. 99-103.
Bhattacharya, A. (2008) Flask Synthesis Promises Untainted Heparin. Chemistry World.
Linhardt, R.J. and N.S. Gunay, Production and chemical processing of low molecular weight heparins. Semin Thromb Hemost, 1999. 25 Suppl 3: 5-16.
Trust, P.C. (2011) After Heparin: Protecting Consumers from the Risk of Substandard and Counterfeit Drugs. 1-101.
2011 [cited 2012; Available from: http://www.researchinchina.com/htmls/report/2010/6019.html.
Powell, B., Heparin's Deadly Side Effects, in Time Magazine. 2008.
Kishimoto, T.K., et al., Contaminated heparin associated with adverse clinical events and activation of the contact system. N Engl J Med, 2008. 358(23): 2457-67.
Bogdanich, W. (2008) Drug Tied to China Had Contaminant, FDA Says. NY TIMES.
Harris, G. (2008) U.S. Identifies Tainted Heparin in Countries. NY Times
Bogdanich, W. (2008) "Heparin Find May Point to Chinese Counterfeiting". NY Times.
Blossom, D.B., et al., Outbreak of adverse reactions associated with contaminated heparin. N Engl J Med, 2008. 359(25): p. 2674-84.
Harris, G. (2008) Chinese Factory Linked to Drug Under Inquiry in U.S. NY Times.
Bogdanich, W. (2008) German Authorities Report Problems With Blood Thinner. NY Times.
Barnes, K.Y. (2008) Heparin Declared "Safe", China Remains Nonchalant. Outsourcing Pharma.com, 1-3.
FDA, Warning Letter to Changzhou SPL Company 2008.
Palmer, E., FDA Triples List of Banned Chinese Heparin Ingredient Makers, in FiercePharma Manufacturing. 2012.
Zawisz, J., FDA Briefing. 2008.
Plamer, E. (2012) FDA Asks Heparin Makers To Test APIs for Contaminants Including BSE. FiercePharma Manufacturing.
Wassener, B. (2010) In China, Strong Debut For Supplier of Heparin. NY Times.
Morrison, N. (2012) USP and FDA Fattens-up QA Standards for Heparin. In-Pharma Technologist.com.
