title: US Food and Drug Administration approval of generic versions of complex biologics: implications for the practicing physician using low molecular weight heparins.
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.
authors.affiliation: Division of Cardiology, Newark Beth Israel Medical Center, 201 Lyons Avenue, Newark, NJ 07112, USA. marcohen@barnabashealth.org
authors.forename: Marc
authors.initials: M
authors.lastname: Cohen
authors.forename: Walter P
authors.initials: WP
authors.lastname: Jeske
authors.forename: Jose C
authors.initials: JC
authors.lastname: Nicolau
authors.forename: Gilles
authors.initials: G
authors.lastname: Montalescot
authors.forename: Jawed
authors.initials: J
authors.lastname: Fareed
mesh_terms: D000818:Animals; D001688:Biological Products / Q000009:adverse effects / Q000592:standards / Q000627:therapeutic use*; D017277:Drug Approval / Q000379:methods*; D016568:Drugs, Generic / Q000009:adverse effects / Q000592:standards / Q000627:therapeutic use*; D006495:Heparin, Low-Molecular-Weight / Q000009:adverse effects / Q000592:standards / Q000627:therapeutic use*; D006801:Humans; D010819:Physician's Role; D017410:Practice Guidelines as Topic / Q000592:standards; D014481:United States
chemical_list: D001688:Biological Products; D016568:Drugs, Generic; D006495:Heparin, Low-Molecular-Weight