The US regulatory and pharmacopeia response to the global heparin contamination crisis.
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.
Biologics and Biotechnology Department, US Pharmacopeia, Rockville, Maryland, USA.
Anita Y
AY
Szajek
Structure Elucidation/Technology Resources, Baxter Healthcare Corporation, Round Lake, Illinois, USA.
Edward
E
Chess
Sjølundsparken, Hellebæk, Denmark.
Kristian
K
Johansen
Boehringer Ingelheim, Ben Venue Laboratories, Inc., Bedford, Ohio, USA.
Gyöngyi
G
Gratzl
National Institute for Biological Standards and Control, South Mimms, Potters Bar, UK.
Elaine
E
Gray
US Food and Drug Administration/Division of Pharmaceutical Analysis, St. Louis, Missouri, USA.
David
D
Keire
Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York, USA.
Robert J
RJ
Linhardt
Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA.
Jian
J
Liu
Biologics and Biotechnology Department, US Pharmacopeia, Rockville, Maryland, USA.
Tina
T
Morris
National Institute for Biological Standards and Control, South Mimms, Potters Bar, UK.|Institute of Pharmaceutical Science King's College London, Franklin Wilkins Building, Waterloo Campus, London, UK.
Barbara
B
Mulloy
R&D, GlaxoSmithKline, Collegeville, Pennsylvania, USA.
Moheb
M
Nasr
Department of Biological Engineering, Harvard-MIT Division of Health Sciences &Technology, Koch institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Zachary
Z
Shriver
Product Development - Analytical Innovation and Development, Fresenius Kabi USA, Skokie, Illinois, USA.
Pearle
P
Torralba
Sanofi, Vitry sur Seine, France.
Christian
C
Viskov
US Pharmacopeia, Rockville, Maryland, USA.
Roger
R
Williams
Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Janet
J
Woodcock
Pfizer Quality Operations Biotech, Chesterfield, Missouri, USA.
Wesley
W
Workman
Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Ali
A
Al-Hakim
D004340:Drug Contamination / Q000331:legislation & jurisprudence* / Q000517:prevention & control*; D014943:Global Health / Q000331:legislation & jurisprudence* / Q000592:standards; D033161:Government Regulation; D006493:Heparin / Q000592:standards*; D007880:Legislation, Drug; D010602:Pharmacopoeias as Topic / Q000592:standards*; D017410:Practice Guidelines as Topic; D011358:Product Surveillance, Postmarketing / Q000592:standards*; D014481:United States; D014486:United States Food and Drug Administration / Q000331:legislation & jurisprudence
D006493:Heparin