The challenge of indication extrapolation for infliximab biosimilars

Biologicals. 2014 Jul;42(4):177-83. doi: 10.1016/j.biologicals.2014.05.005. Epub 2014 Jun 21.


A biosimilar is intended to be highly similar to a reference biologic such that any differences in quality attributes (i.e., molecular characteristics) do not affect safety or efficacy. Achieving this benchmark for biologics, especially large glycoproteins such as monoclonal antibodies, is challenging given their complex structure and manufacturing. Regulatory guidance on biosimilars issued by the U.S. Food and Drug Administration, Health Canada and European Medicines Agency indicates that, in addition to a demonstration of a high degree of similarity in quality attributes, a reduced number of nonclinical and clinical comparative studies can be sufficient for approval. Following a tiered approach, clinical studies are required to address concerns about possible clinically significant differences that remain after laboratory and nonclinical evaluations. Consequently, a critical question arises: can clinical studies that satisfy concerns regarding safety and efficacy in one condition support "indication extrapolation" to other conditions? This question will be addressed by reviewing the case of a biosimilar to infliximab that was approved recently in South Korea, Europe, and Canada for multiple indications through extrapolation. The principles discussed should also apply to biosimilars of other monoclonal antibodies that are approved to treat multiple distinct conditions.

Keywords: Biosimilars; Extrapolation; Immunogenicity; Infliximab; Monoclonal antibodies; Subsequent entry biologics.

Publication types

  • Review

MeSH terms

  • Biosimilar Pharmaceuticals / pharmacokinetics
  • Biosimilar Pharmaceuticals / therapeutic use*
  • Canada
  • Clinical Trials as Topic / standards
  • Drug Approval / methods*
  • Drug-Related Side Effects and Adverse Reactions / immunology
  • Drug-Related Side Effects and Adverse Reactions / metabolism
  • Europe
  • Humans
  • Republic of Korea
  • Therapeutic Equivalency
  • United States
  • United States Food and Drug Administration


  • Biosimilar Pharmaceuticals