title: Scientific considerations in the review and approval of generic enoxaparin in the United States.
abstract: In 2010, the US Food and Drug Administration (FDA) approved a generic low-molecular-weight heparin without clinical safety or efficacy data under the Abbreviated New Drug Application (ANDA) pathway. To enable a determination of active ingredient sameness of generic and innovator enoxaparin products, the FDA developed a scientifically rigorous approach based on five criteria: first, equivalence of physicochemical properties; second, equivalence of heparin source material and mode of depolymerization; third, equivalence in disaccharide building blocks, fragment mapping and sequence of oligosaccharide species; fourth, equivalence in biological and biochemical assays; and finally, equivalence of in vivo pharmacodynamic profile. In addition to fulfillment of these criteria, FDA also used in vitro, ex vivo and model animal data to ensure there was no increased immunogenicity risk of the generic enoxaparin product relative to the brand name product. The approval of the highly complex enoxaparin product using this framework under the ANDA pathway represents a major development. It also suggests that analytical and scientific advancements may in certain cases allow the elimination of unnecessary in vivo testing in animals and humans.
authors.affiliation: Office of Generic Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Rockville, Maryland, USA.
authors.forename: Sau
authors.initials: S
authors.lastname: Lee
authors.forename: Andre
authors.initials: A
authors.lastname: Raw
authors.forename: Lawrence
authors.initials: L
authors.lastname: Yu
authors.forename: Robert
authors.initials: R
authors.lastname: Lionberger
authors.forename: Naiqi
authors.initials: N
authors.lastname: Ya
authors.forename: Daniela
authors.initials: D
authors.lastname: Verthelyi
authors.forename: Amy
authors.initials: A
authors.lastname: Rosenberg
authors.forename: Steve
authors.initials: S
authors.lastname: Kozlowski
authors.forename: Keith
authors.initials: K
authors.lastname: Webber
authors.forename: Janet
authors.initials: J
authors.lastname: Woodcock
mesh_terms: D002240:Carbohydrate Sequence; D017277:Drug Approval; D016568:Drugs, Generic / Q000737:chemistry; D017984:Enoxaparin / Q000737:chemistry*; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D016568:Drugs, Generic; D017984:Enoxaparin; D009844:Oligosaccharides