TY  - JOUR
T1  - Mechanism-Based Extrapolation across Biosimilar Indications, Patient Populations, Dosing Regimens, and Residual Scientific Uncertainty in Regulatory and Clinical Contexts
A1  - Gabriel Costa
A1  - Lucas Ribeiro
A1  - Ricardo Alves
A1  - Mariana Lopes
JF  - International Journal of Pharmaceutical Research and Allied Sciences
JO  - Int J Pharm Res Allied Sci
SN  - 2277-3657
Y1  - 2025
VL  - 14
IS  - 3
DO  - 10.51847/0LDc77Lo94
SP  - 73
EP  - 82
N2  - 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 functional evidence, indication-specific mechanisms of action, target-expression and disease-pathway context, exposure and regimen bridging, population and immunogenicity modifiers, residual scientific uncertainty, evidence coherence, and post-authorization evidence updating. The framework treats residual uncertainty as an explicit scientific object whose source, potential consequence, affected scope, and feasible resolution strategy must be documented. It distinguishes conditionally supported extrapolation from situations requiring targeted additional evidence or leaving the extrapolation claim unsupported under the current evidence package. Immunogenicity is framed as a context-dependent interaction among product attributes, patient characteristics, disease state, concomitant treatment, route, treatment duration, prior exposure, and assay performance. Clinical communication, traceability, and post-authorization monitoring are included because evidentiary adequacy does not guarantee correct interpretation or implementation. The principal contribution is a transparent, non-empirical architecture connecting product comparison to indication-, population-, and regimen-specific decision boundaries. The framework does not constitute a validated predictive model, clinical recommendation, regulatory determination, or universal development standard. Prospective operationalization, inter-rater reproducibility testing, product-class adaptation, and empirical validation are required before formal use.
UR  - https://ijpras.com/article/mechanism-based-extrapolation-across-biosimilar-indications-patient-populations-dosing-regimens-a-luqmfqbqkgkr2m5
ER  -