Global Biosimilar Rules Diverge Across WHO Regions, Limiting Patient Access

Wide variation in how countries define, evaluate, and approve biosimilar medications may be undermining access to more affordable biological treatments—and a new comparative analysis lays out exactly where those gaps are widest.

Global review reveals uneven biosimilar rules on waivers, interchangeability, and safety tracking—barriers to cheaper biologics and approvals. | Image credit: Tex vector - stock.adobe.com

A scoping review published in JAMA Health Forum examined biosimilar regulatory frameworks across all 6 World Health Organization (WHO) regions, finding persistent inconsistencies in how countries approach comparability requirements, clinical study waivers, interchangeability designation, and pharmacovigilance—differences that may complicate the approval process and limit medication availability.¹

Why Regulatory Divergence Matters for Biosimilar Access

Clinicians and policymakers who review biosimilar data from other countries often assume those data were produced under standards similar to their own. That assumption, the researchers noted, may be incorrect—and acting on it could introduce bias about a biosimilar's validated safety and efficacy profile. Although the WHO, FDA, and European Medicines Agency (EMA) have each issued guidance frameworks, countries have adopted them unevenly. The need to map those differences systematically became the foundation of the review.

That concern is not new to the field. A 2025 descriptive review published in Therapeutic Innovation & Regulatory Science examined individual national regulatory requirements and guidelines for biosimilars in more than 70 countries as of July 2024—including both emerging countries and those with extensive biosimilar experience—and similarly identified key differences that complicate global development efforts.² Together, the 2 analyses paint a consistent picture of a regulatory landscape that has yet to cohere around shared standards.^1,2

Study Design and Countries Examined

The present scoping review followed PRISMA Extension for Scoping Reviews (PRISMA-ScR) methodology, searching CINAHL, PubMed, and Scopus databases through March 1, 2026, and drawing on 37 regulatory guidance documents from 19 countries.¹ Twelve were classified as emerging and developing economies and 7 as advanced economies by the International Monetary Fund. The advanced economies—Canada, France, Germany, Japan, South Korea, the UK, and the US—served as comparators given their longer histories of biosimilar development. Emerging and developing economies spanned all 6 WHO regions, including Brazil, China, Egypt, India, Indonesia, Mexico, Nigeria, the Philippines, Poland, Saudi Arabia, Tanzania, and Turkey. No patient demographic data were collected, as the study examined regulatory documents rather than clinical outcomes.

Where Countries Agreed—and Where They Didn't

Most countries (n = 17 of 19; 89%) had adopted WHO biosimilar terminology, and the same proportion defined biosimilarity as the absence of meaningful differences in quality, safety, and efficacy compared with the reference product. Sixteen countries explicitly required comparability exercises, although Mexico, Indonesia, and China did not clearly include this requirement.

Gaps widened on more complex regulatory questions. All 7 advanced economies allowed waivers of clinical efficacy and immunogenicity testing when sufficient analytical data were available—consistent with updated 2022 WHO guidance. Among emerging and developing economies, only a subset had adopted comparable waiver policies, with Tanzania still requiring clinical efficacy studies in every case.

Interchangeability guidance, which determines whether a biosimilar can be substituted for its reference product, sometimes at the pharmacy level without physician consultation, appeared in the guidance documents of only 2 of the 12 emerging and developing economies studied: Nigeria and Poland. Nigeria's guidance, notably, explicitly discouraged substitution, citing pharmacovigilance concerns.

"These findings highlight areas in which the global regulatory framework requires greater harmonization to optimize access to biosimilar medications and to improve support for policy research and cross-country comparisons," the authors wrote.

Pharmacovigilance and Naming Requirements Add Complexity

Eleven countries required a pharmacovigilance plan as part of a biosimilar application. Japan, the Philippines, and the Republic of Korea were the only countries that explicitly mandated postmarketing pharmacovigilance studies. Guidance on biosimilar naming and labeling—important for adverse event tracking—was present in only 8 of the 19 countries examined.

Some official guidance documents were only available in their country's native language, creating the possibility of translation errors despite the use of DeepL Translate software. The researchers also could not confirm they had captured every official guidance document, as some countries distribute regulatory requirements across multiple publications. Guidance documents drafted but not made publicly available would not have been captured. Additionally, Indonesia was reclassified from the WHO South-East Asia region to the Western Pacific region in mid-2025, although all 6 WHO regions remained represented in the final analysis.

For US payers and managed care organizations tracking global biosimilar pipelines, the findings underscore the risk of equating international biosimilar evidence with FDA-reviewed data. The study also signals opportunity: the FDA's June 2024 draft guidance eliminating the requirement for switching studies, and its November 2025 draft guidance reducing the need for comparative clinical efficacy data in favor of analytical justifications, may position the US as a potential model for streamlined approval that other national regulatory agencies could follow.

References

1. Watanabe JH, Strand MW, Walvekar M, Alfonso-Cristancho R. Regulatory definitions and classification of biosimilar medications across the 6 regions of the World Health Organization: a scoping review. JAMA Health Forum. 2026;7(5):e261642. doi:10.1001/jamahealthforum.2026.1642
2. Kirchlechner TM, Cohen HP. Global harmonization of biosimilar development by overcoming existing differences in regional regulatory requirements — outcomes of a descriptive review. Ther Innov Regul Sci. 2025;59(2):245-255. doi:10.1007/s43441-024-00740-4