title: Biosimilar monoclonal antibodies: the scientific basis for extrapolation.
abstract: BACKGROUND
  Biosimilars are biologic products that receive authorization based on an abbreviated regulatory application containing comparative quality and nonclinical and clinical data that demonstrate similarity to a licensed biologic product. Extrapolation of safety and efficacy has emerged as an important way to simplify biosimilar development. Regulatory authorities have generally reached the consensus that extrapolation of similarity from one indication to other approved indications of the reference product can be permitted if it is scientifically justified.
  
  
  METHODS
  Recently, the first biosimilar, biosimilar infliximab (Remsima/Inflectra) to the innovator monoclonal antibody infliximab (Remicade), was approved in the European Union, Canada and South Korea; the USA subsequently approved its first biosimilar, a less complex molecule (filgrastim-sndz). Based on two clinical trials of biosimilar infliximab in patients with rheumatoid arthritis and ankylosing spondylitis, the European Medicines Agency allowed extrapolation to all eight approved indications for innovator infliximab, whereas Health Canada did not permit extrapolation to the indications for ulcerative colitis and Crohn's disease. These differing decisions on extrapolation of indications for biosimilar infliximab highlight important unanswered regulatory and scientific questions. Here, we propose substantive scientific considerations for indication extrapolation.
  
  
  CONCLUSIONS
  The preclinical and clinical criteria that are currently required to merit indication extrapolation have not been rigorously evaluated.
authors.affiliation: a 1 Utrecht University, Departments of Pharmaceutical Sciences and Innovation Studies , Utrecht, The Netherlands.
authors.forename: Huub
authors.initials: H
authors.lastname: Schellekens
authors.affiliation: b 2 University of Missouri School of Law , Columbia, MO, USA.
authors.forename: Erika
authors.initials: E
authors.lastname: Lietzan
authors.affiliation: c 3 AbbVie Inc., Biotherapeutics, Global Medical Affairs , 9615 Los Romeros Avenue, Suite 700, San Juan, PR, USA +1 787 622 5454 ; +1 787 276 3016 ; freddy.faccin@abbvie.com.
authors.forename: Freddy
authors.initials: F
authors.lastname: Faccin
authors.affiliation: d 4 AbbVie Inc., Biotherapeutics, Global Medical Affairs, Biologics Strategic Development , North Chicago, IL, USA.
authors.forename: Jaap
authors.initials: J
authors.lastname: Venema
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D059451:Biosimilar Pharmaceuticals / Q000378:metabolism* / Q000627:therapeutic use; D003424:Crohn Disease / Q000188:drug therapy; D006801:Humans; D000069285:Infliximab / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use; D013167:Spondylitis, Ankylosing / Q000188:drug therapy; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D059451:Biosimilar Pharmaceuticals; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab
keywords: TNF inhibitors; biosimilars; extrapolation; infliximab; monoclonal antibodies