The contamination of the widely used lifesaving anticoagulant drug heparin in 2007 has drawn renewed attention to the challenges that are associated with the characterization, quality control and standardization of complex biological medicines from natural sources. Heparin is a linear, highly sulfated polysaccharide consisting of alternating glucosamine and uronic acid monosaccharide residues. Heparin has been used successfully as an injectable antithrombotic medicine since the 1930s, and its isolation from animal sources (primarily porcine intestine) as well as its manufacturing processes have not changed substantially since its introduction. The 2007 heparin contamination crisis resulted in several deaths in the United States and hundreds of adverse reactions worldwide, revealing the vulnerability of a complex global supply chain to sophisticated adulteration. This Perspective discusses how the US Food and Drug Administration (FDA), the United States Pharmacopeial Convention (USP) and international stakeholders collaborated to redefine quality expectations for heparin, thus making an important natural product better controlled and less susceptible to economically motivated adulteration.
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The authors appreciate the financial and logistical support provided by USP; the contributions of USP volunteers, the scientific community, and the collaborating laboratories; the public comments; and the collaboration of the FDA, including helpful review and discussion.
A.Y.S., K.J., G.G., E.G., T.M., B.M., M.N., R.W., J.W., D.K. and A. A.-H. declare no competing financial interests. R.J.L. declares competing interest in the form of funding derived from the NIH in the form of research grants in the area of heparin analysis and regularly consults on heparin analysis. J.L. declares competing interest in the form of funding derived from the NIH and FDA in the form of research grants in the area of heparin. J.L. is a founder of Glycan Therapeutics, LLC. C.V. is an employee of Sanofi and has financial interest in the company. E.K.C. was a stockholder and employee of Baxter Healthcare Corporation during the completion of this work. W.E.W. is an employee of Pfizer and has financial interest in the company.
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Szajek, A., Chess, E., Johansen, K. et al. The US regulatory and pharmacopeia response to the global heparin contamination crisis. Nat Biotechnol 34, 625–630 (2016). https://doi.org/10.1038/nbt.3606
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