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Streamlining the biosimilars playbook: What March 2026 FDA and EMA changes mean for developers

Recent years have seen numerous regulatory shifts for biosimilars. Two decades after the first biosimilar was approved by the European Medicines Agency (EMA) in 2006, researchers and regulatory authorities have enhanced understanding of what is necessary to develop safe, effective biosimilars. Combined with the desire to encourage competition and therapeutic access, this knowledge has led to efforts to streamline biosimilar development through updated regulatory policy and guidance.

The resulting changes hold great potential to reduce biosimilar development costs and timelines, however they also necessitate shifts in strategy for developers. Here, we explore two major March 2026 regulatory changes from the EMA and U.S. Food and Drug Administration (FDA) and their potential ramifications.

EMA: Waiving certain comparative efficacy studies

On 16 March 2026, the EMA finalised its “Reflection Paper on a Tailored Clinical Approach in Biosimilar Development.”1 This guidance reflects several years of reassessing the need for comparative efficacy studies (CES), which have traditionally followed pharmacokinetic similarity studies (PKSS) to demonstrate biosimilarity in humans. It clarifies that, when specific criteria are met - particularly when the biosimilar’s structural and functional properties can be well characterised - comparative clinical efficacy studies assessing efficacy and immunogenicity may be waived. This pathway is limited however, as more complex or less well-characterised therapies will likely continue to require CES.

To justify waiving or downscoping CES, developers must generate more robust evidence earlier in development, with greater reliance on analytical comparability and pharmacokinetic data. Detailed physicochemical and functional characterisation of the biosimilar relative to the reference product will be critical for establishing quality, consistency and safety often requiring more advanced analytical approaches. A bioanalysis, particularly the measurement of drug pharmacokinetics and immunogenicity through validated assays, becomes increasingly important, necessitating high confidence in assay performance, reliability and interpretation.

Developers should carefully consider the trial design implications of relying on standalone pharmacokinetic similarity studies (PKSS) to demonstrate bioequivalence. Waiving comparative efficacy studies can increase the required PKSS sample size to achieve statistical equivalence with the reference product. This challenge is amplified for highly bioavailable biologics that must be studied in patients—such as in oncology—where identifying qualified and willing sites and patients for intensive PK studies is already difficult. Increasing patient numbers in studies that require frequent blood sampling further compounds recruitment and operational hurdles.

Participation can also be limited by the availability of established reference products, reducing patient interest in clinical trials, while many sites lack the staffing or infrastructure to support demanding PK protocols. In addition, PKSS are often abbreviated and may not allow patients to receive a full labelled course of therapy, making these studies less attractive to both patients and sites, which may prioritise trials offering access to novel therapies.

To mitigate these risks, developers should design PKSS to minimise patient burden by optimising sampling schedules, using sparse pharmacokinetic designs and considering alternative blood collection methods. Additional measures—such as travel reimbursement, home health services and post‑trial expanded access programs—can further support recruitment, retention and site participation.

The EMA’s regulatory shift away from comparative efficacy studies has taken place in parallel with evolving positions of other regulatory bodies, including those in the US and Canada. It enables developers to avoid the high costs and lengthy timelines associated with these studies, significantly lowering barriers to market entry. While this is likely to be beneficial in the long run, it will also increase competition as smaller, agile biotech companies globally are better able to participate in biosimilar development. As a result, Sponsors will need to start planning and development strategies early, collecting robust comparative analytical and manufacturing data for their initial submission package, garner early regulatory agreement for their product development plan to avoid development delays and to differentiate their biosimilar product in this more competitive landscape.

FDA: Simplifying global logistics

On 09 March 2026, the FDA issued the fourth revision of “New and Revised Draft Q&As on Biosimilar Development and the BPCI Act.”2 A key update simplifies the use of non-US-licensed reference products in global clinical trials. Previously, the FDA required a three-way pharmacokinetic study comparing the biosimilars, a US-licensed reference product and a non-US-licensed comparator. Under this revised guidance, this requirement may now be waived if sufficient evidence demonstrates that the non-US-licensed product is representative of the US-licensed reference product, eliminating the need to include the US comparator in biosimilar clinical trials.

This revision has significant implications for the design and conduct of international biosimilar trials. Sourcing US-licensed reference product for global studies is often costly and logistically complex, with country-specific importation, regulatory and legal hurdles to navigate. Eliminating the need to procure large quantities of a US-licensed product streamlines global development and data collection acceptable for FDA submission. This change is also expected to reduce biosimilar development costs by approximately $20 million per program.3

As with the waiving of comparative efficacy studies, lowering these barriers is likely to encourage greater competition, in the US biosimilars market specifically. In order to remain competitive, biosimilar developers will need to adopt a more strategic approach to study design and commercialisation. 

An evolving field

As the biosimilars landscape continues to evolve, more regulatory shifts are likely. With agencies around the world prioritising streamlined processes, encouraging competition and aligning global standards, this is an area poised for continued change. Biosimilar developers will need to stay alert and agile to respond quickly and effectively to these changes.

To learn more about the shifting biosimilars landscape, including how changing regulations impact development processes and what developers should consider when building a strategy for market entry, download our whitepaper. If you would like to discuss the biosimilars sector with any of our experienced team, please Contact Us.

References

  1. European Medicines Agency. Reflection Paper on a Tailored Clinical Approach in Biosimilar Development. 16 Mar. 2026, https://www.ema.europa.eu/en/documents/other/reflection-paper-tailored-clinical-approach-biosimilar-development_en.pdf-0
  2. Center for Drug Evaluation and Research. New and Revised Draft Q&As on Biosimilar Development and the BPCI Act (Revision 4). 9 Mar. 2026, https://www.fda.gov/regulatory-information/search-fda-guidance-documents/new-and-revised-draft-qas-biosimilar-development-and-bpci-act-revision-4.
  3. Office of the Commissioner. “FDA Takes Further Steps to Streamline Biosimilar Development and Make Medicines More Affordable.” FDA, 9 Mar. 2026, https://www.fda.gov/news-events/press-announcements/fda-takes-further-steps-streamline-biosimilar-development-and-make-medicines-more-affordable
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