Learn how biosimilars leverage the indications of the reference product 2

Extrapolation is an important concept for biosimilars. Although the FDA may approve a biosimilar for all of the indications of its reference product, the biosimilar’s manufacturer may have only conducted clinical trials that were adequately sensitive to detect clinically meaningful differences between the two products, and for one or two representative indications. 2

In addition:

  • Indication extrapolation refers to a biosimilar being approved for indications that were not evaluated during the biosimilar’s clinical trials, and scientific justification must be provided to support the rationale of extrapolation for each condition of use 2
  • Scientific justification is provided through an assessment of the mechanism(s) of action; pharmacokinetics, pharmacodynamics, and bio-distribution in different patient populations; immunogenicity in different patient populations; differences in expected toxicities; and, other factors that may affect safety and efficacy 8
  • Based on scientific justification, and given the complexities of the science behind extrapolation, it may not be appropriate in all cases 2
  • The FDA recommends that a biosimilar manufacturer choose a condition of use that would be adequately sensitive to detect clinically meaningful differences between the biosimilar and reference product 2
  • In some cases, healthy volunteers may be the most sensitive population to study when seeking to reveal differences in immune responses, as healthy volunteers are not immunocompromised and, therefore, will exhibit normal immune responses 2

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