Biopharmaceuticals have transformed treatment across oncology, immunology, and other therapeutic fields, but their molecular heterogeneity, manufacturing dependence, immunogenic potential, and cost complicate development and access. Biosimilars seek to expand competition without reproducing an originator’s proprietary manufacturing process or exact molecular microheterogeneity. This integrative review examines how evidence from manufacturing knowledge, analytical and functional comparability, comparative pharmacokinetics, residual clinical investigation, immunogenicity assessment, switching studies, pharmacovigilance, and market implementation contributes to biosimilar evaluation. Heterogeneous evidence was compared according to the question it can resolve, its sensitivity, relevance to decision-making, and remaining uncertainty. Analytical and functional comparison carries the greatest discriminatory burden, whereas pharmacokinetic, pharmacodynamic, clinical, and immunogenicity evidence should address defined residual questions rather than repeat information already provided by more sensitive methods. Nevertheless, strong comparability evidence does not automatically establish interchangeability, substitution policy, market uptake, or patient access. Remaining tensions concern the clinical meaning of small quality-attribute differences, circumstances in which confirmatory efficacy studies may be reduced, generalizability of multiple-switch evidence, sufficiency of streamlined immunogenicity assessment, traceability limitations, and sustainability of price-based competition. A molecule-to-market interpretation therefore requires linked but non-interchangeable scientific, clinical, surveillance, and implementation domains. Biosimilar evaluation is best understood as a bounded totality-of-evidence process in which each evidence type has a distinct inferential role and downstream use remains context-dependent.
IJPRAS
