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US Food and Drug Administration approval of generic versions of complex biologics: implications for the practicing physician using low molecular weight heparins

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Abstract

Low-molecular-weight heparins (LMWHs) have shown equivalent or superior efficacy and safety to unfractionated heparin as antithrombotic therapy for patients with acute coronary syndromes. Each approved LMWH is a pleotropic biological agent with a unique chemical, biochemical, biophysical and biological profile and displays different pharmacodynamic and pharmacokinetic profiles. As a result, LMWHs are neither equipotent in preclinical assays nor equivalent in terms of their clinical efficacy and safety. Previously, the US Food and Drug Administration (FDA) cautioned against using various LMWHs interchangeably, however recently, the FDA approved generic versions of LMWH that have not been tested in large clinical trials. This paper highlights the bio-chemical and pharmacological differences between the LMWH preparations that may result in different clinical outcomes, and also reviews the implications and challenges physicians face when generic versions of the original/innovator agents are approved for clinical use.

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Abbreviations

ACS:

Acute coronary syndromes

ANDA:

Abbreviated new drug approval

EMA:

European Medicines Agency

FDA:

United States Food and Drug Administration

HIT:

Heparin-induced thrombocytopenia

LMWH:

Low-molecular-weight heparin

PCI:

Percutaneous coronary intervention

PK/PD:

Pharmacokinetic/pharmacodynamic

UA/NSTEMI:

Unstable angina/non-ST-elevation myocardial infarction

UFH:

Unfractionated heparin

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Conflict of interest

Dr. Cohen has received/receives grant/research support from Sanofi, Johnson & Johnson, and Bristol-Myers Squibb. Served as a consultant to Datascope (now Maquet), Merck, and Sanofi-Aventis; member of the speaker bureau for Sanofi, Merck, and Bristol-Meyers Squibb, Boehringer Ingelheim, AstraZeneca, and Janssen. Dr. Jeske has received honoraria from Sanofi. Dr. Nicolau has research grant funding and/or honoraria from AstraZeneca, Bayer, Daiichi Sankyo, Eli Lilly & Co, Johnson & Johnson; GlaxoSmithKline; Merck, and Pfizer. Served as a consultant/advisory board member for AstraZeneca, Sanofi, and Merck. Dr. Montalescot has received grant and research support from Sanofi, Eli Lilly & Co, and Guerbet; received honoraria from Sanofi-Aventis, Eli Lilly & Co, GlaxoSmithKline, Merck, The Medicine’s Company, and Pfizer; and served on advisory boards for Sanofi-Aventis, Eli Lilly & Co, GlaxoSmithKline, Merck, The Medicine’s Company, and Schering Plough. Dr. Fareed has received honoraria from Sanofi.

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Authors and Affiliations

  1. Division of Cardiology, Newark Beth Israel Medical Center, 201 Lyons Avenue, Newark, NJ, 07112, USA

    Marc Cohen

  2. Loyola School of Medicine, Chicago, IL, USA

    Walter P. Jeske & Jawed Fareed

  3. Heart Institute (InCor)–Hospital das Clinicas da Faculdade de Medicina da, Universidade de São Paulo, São Paulo, Brazil

    Jose C. Nicolau

  4. Service de Cardiologie, Pitié-Salpétrière Hospital, Paris, France

    Gilles Montalescot

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  1. Marc Cohen
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  2. Walter P. Jeske
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  3. Jose C. Nicolau
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  4. Gilles Montalescot
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  5. Jawed Fareed
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Correspondence to Marc Cohen.

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Cohen, M., Jeske, W.P., Nicolau, J.C. et al. US Food and Drug Administration approval of generic versions of complex biologics: implications for the practicing physician using low molecular weight heparins. J Thromb Thrombolysis 33, 230–238 (2012). https://doi.org/10.1007/s11239-012-0680-3

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  • DOI: https://doi.org/10.1007/s11239-012-0680-3

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