Abstract

Rita Mourya, Shweta Gogate, Murtuza Zaki, Neeraj Mourya

ABSTRACT

Background. Biosimilars are biological medicines demonstrated to be highly similar to an already-licensed reference biologic, offering a route to lower-cost access to biologic therapy. Because these molecules are large, heterogeneous and manufactured in living systems, they cannot be shown to be identical to the originator; regulators therefore rely on a stepwise, comparability-based 'totality-of-evidence' paradigm rather than on the abbreviated bioequivalence pathway used for small-molecule generics. Objective. To systematically compare the regulatory requirements for biosimilar approval across the principal frameworks—the US FDA, the European Medicines Agency (EMA), the World Health Organization (WHO) and India's CDSCO—and to characterise the convergent 2022–2026 shift toward reduced, analytically-driven ('tailored') clinical data packages. Methods. A structured literature and regulatory-document search (PubMed, Scopus, Embase, Web of Science and the FDA, EMA, WHO and CDSCO repositories) was conducted following PRISMA 2020 principles. Guidance documents, primary regulatory texts and peer-reviewed analyses published up to mid-2026 were screened against pre-specified eligibility criteria and synthesised qualitatively across eight comparative domains. Results. All four frameworks share a common scientific core—comparative analytical characterisation as the foundation, supported by in vitro pharmacology, comparative pharmacokinetics and case-by-case clinical evaluation—but differ in legal basis, terminology, reference-product sourcing, interchangeability policy and post-marketing obligations. As of December 2025 the FDA had approved roughly 90 biosimilars (18 in 2025 alone) and the EMA more than 85 since 2006. A marked regulatory convergence occurred in 2022–2026: WHO (2022), the EMA reflection paper (adopted March 2026), the FDA draft guidance (October 2025) and India's 2025 draft all move to make comparative efficacy studies the exception rather than the default, relying instead on state-of-the-art analytical comparability plus a comparative pharmacokinetic study. Conclusion. Global biosimilar regulation is converging on a leaner, science-driven model that preserves rigorous quality and pharmacovigilance standards while lowering development cost and time. Remaining divergence—chiefly around the US 'interchangeability' designation and national substitution rules—represents the principal frontier for further harmonisation.