Mechanism-Based Extrapolation across Biosimilar Indications, Patient Populations, Dosing Regimens, and Residual Scientific Uncertainty in Regulatory and Clinical Contexts

Indication extrapolation allows a biosimilar to be used in approved reference-product indications that were not independently tested in comparative efficacy trials. Its scientific justification, however, cannot rest on analytical similarity, shared target identity, pharmacokinetic equivalence, or clinical similarity in one sensitive population alone. This original framework article proposes a mechanism-based evidence pathway integrating reference-product knowledge, comparative analytical and fun