title: Active and passive surveillance of enoxaparin generics: a case study relevant to biosimilars.
abstract: OBJECTIVE
  This retrospective analysis assessed the capability of active and passive safety surveillance systems to track product-specific safety events in the USA for branded and generic enoxaparin, a complex injectable subject to immune-related and other adverse events (AEs).
  
  
  METHODS
  Analysis of heparin-induced thrombocytopenia (HIT) incidence was performed on benefit claims for commercial and Medicare supplemental-insured individuals newly treated with enoxaparin under pharmacy benefit (1 January 2009 - 30 June 2012). Additionally, spontaneous reports from the FDA AE Reporting System were reviewed to identify incidence and attribution of enoxaparin-related reports to specific manufacturers.
  
  
  RESULTS
  Specific, dispensed products were identifiable from National Drug Codes only in pharmacy-benefit databases, permitting sensitive comparison of HIT incidence in nearly a third of patients treated with brand or generic enoxaparin. After originator medicine's loss of exclusivity, only 5% of spontaneous reports were processed by generic manufacturers; reports attributable to specific generics were approximately ninefold lower than expected based on market share.
  
  
  CONCLUSIONS
  Claims data were useful for active surveillance of enoxaparin generics dispensed under pharmacy benefits but not for products administered under medical benefits. These findings suggest that the current spontaneous reporting system will not distinguish product-specific safety signals for products distributed by multiple manufacturers, including biosimilars.
authors.affiliation: Amgen, Inc. , 4000 Nelson Rd, Longmont, CO 80503 , USA +1 303 401 2587 ; +1 303 401 4404 ; ginog@amgen.com.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Grampp
authors.forename: Machaon
authors.initials: M
authors.lastname: Bonafede
authors.forename: Thomas
authors.initials: T
authors.lastname: Felix
authors.forename: Edward
authors.initials: E
authors.lastname: Li
authors.forename: Michael
authors.initials: M
authors.lastname: Malecki
authors.forename: J Michael
authors.initials: JM
authors.lastname: Sprafka
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects; D059451:Biosimilar Pharmaceuticals / Q000008:administration & dosage / Q000009:adverse effects*; D016568:Drugs, Generic / Q000008:administration & dosage / Q000009:adverse effects*; D017984:Enoxaparin / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D011358:Product Surveillance, Postmarketing / Q000379:methods; D012189:Retrospective Studies; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000453:epidemiology; D014481:United States / Q000453:epidemiology
chemical_list: D000925:Anticoagulants; D059451:Biosimilar Pharmaceuticals; D016568:Drugs, Generic; D017984:Enoxaparin
keywords: biosimilar; enoxaparin; pharmacovigilance; safety surveillance