Kimberly Salgado is Head of Centre for Biosimilar Drug Development, ICON plc

Kimberly Salgado

Scientist working in biosimilars development with futuristic medical technology and digital interface elements | Image Credit: ©KHAN VECTOR CO. -stock.adobe.com

Since 2024, new guidance from the FDA and the European Medicines Agency (EMA) has advanced efforts to streamline biosimilar development. Biosimilars—products created to closely emulate the mechanism of action, safety, and efficacy of reference biologic products whose patents have expired—encourage competition and lower prices in the biologics market. Because of this, they are critical to enhancing patient access to biologic therapies and decreasing pressure on healthcare budgets.

Although biosimilars typically cost less to develop than novel biologics, it has historically been challenging for developers to balance return on investment with the lower prices markets expect from biosimilars. As a result, changes to regulatory guidelines that reduce costs and expedite approval processes are invaluable in encouraging the continued development of biosimilars.

While these changes to regulatory approaches will ultimately reduce the time and resources required to develop biosimilars, they also represent a fundamental shift in strategies for biosimilar submissions. Understanding the implications of the new regulatory guidance and publications, including their impact on data generation and the competitive landscape, will be crucial to future success in the biosimilar field.

What Are the Key Changes to EMA and FDA Regulations?

There is a considerable amount of new biosimilar regulatory information to review, both in the European Union or the United States. For the EMA, relevant documents include the recently released 

Reflection Paper on a Tailored Clinical Approach in Biosimilar Development

 and the “Workshop on a Tailored Clinical Approach in Biosimilar Development.”

One of the most important takeaways from these updates is the idea that in certain cases, in which physiochemical and functional properties can be well characterized, such as with state-of-the-art analytical tools, comparative efficacy studies may not be required. Reducing the need for such studies, which typically assess a biosimilar’s efficacy and immunogenicity in humans, would give sponsors the means to eliminate a major time- and resource-consuming element of biosimilar development. However, it is important to note that comparative efficacy studies will still play an important role in biosimilars that are difficult to characterize or have a poorly understood mechanism of action.

The FDA also released multiple documents with guidance intended to encourage biosimilar development, while reducing timelines and cost. These include theBiosimilars Action Plan, as well as the draft guidance documents 

Development of Therapeutic Protein Biosimilars: Comparative Analytical Assessment and Other Quality-Related Considerations

Considerations in Demonstrating Biosimilarity to a Reference Product: Updated Recommendations for Assessing the Need for Comparative Efficacy Studies

Similarly to the EMA, the FDA’s updates reexamine the clinical development pathway required for approval, placing greater weight on pharmacokinetic (PK) similarity studies and suggesting that clinical comparative efficacy studies may not be required. They also increase the emphasis on comparative analytical assessment, which includes a biosimilar’s structure, function, process and product‐related attributes.

New and Revised Draft Q&As on Biosimilar Development and the BPCI Act

 A central change in this guidance is that it is acceptable for clinical studies to compare a biosimilar candidate to a reference product that is approved in another country, but not in the US. This allows developers to avoid the high costs and supply challenges often associated with procuring US-licensed biologics, while facilitating a single global development program. In such cases, the sponsor must prove through robust analytical data that the non-US-licensed comparator product has sufficient similarity to a US-approved biologic product to be relevant.

Previously, sponsors were required to conduct a three-way PK study comparing the biosimilar candidate with both the US-approved reference product and the non-US-approved comparator. This change is likely to streamline the ability of internationally based developers to have their biosimilar approved for use in the US by reducing development costs by an estimated $20 million per program.

What Are Some Considerations for Data Collection?

These regulatory shifts have important implications for how biosimilar developers design and generate evidence. Traditionally, clinical comparative efficacy studies have been a central component of biosimilar development, providing in-human confirmation of similarity. However, waiving comparative efficacy studies, one of the central sources of in-human biosimilar data, has serious ramifications for how sponsors need to collect and prioritize information.

In particular, it means that the information revealed by PK studies will be much more significant. As preclinical and PK data take on a greater role in demonstrating biosimilarity, regulatory authorities have heightened expectations for more sophisticated and sensitive analytical development and testing, as well as robust bioanalytical methodologies and analyses.

With the increased emphasis on analytical comparability, including chemistry, manufacturing and controls, the link between manufacturing processes and analytical attributes becomes more visible. To meet the rising level of scrutiny, developers will need to employ more extensive and in-depth physiochemical characterization, along with stronger process and product-related characterization. In parallel, risk assessments must clearly define which analytical differences between the biosimilar and reference product are acceptable and which are not.

For bioanalysis, which assesses a drug’s behavior in a biological system, the potential reduction of full comparative efficacy trials places greater weight on assay performance and interpretation. High confidence in assay validity is therefore essential. This includes developing well-validated assays to quantify PK, pharmacodynamic biomarkers, and immunogenicity, such as anti-drug antibodies or neutralizing antibodies. A central focus during development must be on assay reproducibility. And a one-assay approach, designed to assess the biosimilar and its reference product equivalently without introducing bias, can be particularly important in generating high-confidence results.

With regulatory authorities making a concerted effort to streamline biosimilar development, sponsors are poised to benefit. However, companies that have not historically developed biosimilars are also recognizing the opportunity represented by these shifts. The lower barrier to entry presented by shortened timelines and reduced expenses means that more small, agile organizations are entering the market. As a result, biosimilar competition is on the rise.

International developers, such as biotechs based in China, have also contributed to rising competition in European and US markets, partly through partnerships with global pharmaceutical companies. The March 2026 FDA guidance is expected to further accelerate this trend in the US.

Biosimilars developed for non-US markets will be eligible for FDA consideration as long as their non-US reference product is proven to be sufficiently similar to a US-approved biologic. Additionally, clinical studies conducted abroad will no longer need to pay high shipment or import fees, or navigate complex legal processes, to obtain large quantities of a US comparator for submission to the FDA for US approval.

Amidst this influx of competition and regulatory pathways, presenting robust supporting data will be a critical differentiator for sponsors. It will be necessary to pay close attention to regional standards and the regulatory requirements of each intended market to avoid delays associated with data collection, which might give competitors an advantage.

Staying Ready for the Future of Biosimilars

Regulatory authorities have made it clear that streamlining biosimilar development is a priority, with additional countries, such as Canada, poised to follow the EU and US’ example in reducing the requirements for comparative efficacy studies. Although these changes are likely beneficial, they are not without challenges for sponsors seeking to take advantage of them. As the regulatory landscape continues to evolve, sponsors must embrace agility and be prepared to respond dynamically.

Reflection Paper on a Tailored Clinical Approach in Biosimilar Development. EMA. March 16, 2026. Accessed June 3, 2026. 

https://www.ema.europa.eu/en/documents/other/reflection-paper-tailored-clinical-approach-biosimilar-development_en.pdf-0

Workshop on a tailored clinical approach in biosimilar development–Meeting Report. EMA. September 22, 2025. Accessed June 3, 2026. 

https://www.ema.europa.eu/en/documents/report/meeting-report-workshop-tailored-clinical-approach-biosimilar-development_en.pdf

Biosimilars Action Plan. FDA. September 2025. Accessed June 3, 2026. 

https://www.fda.gov/drugs/biosimilars/biosimilars-action-plan

Development of Therapeutic Protein Biosimilars: Comparative Analytical Assessment and Other Quality-Related Considerations, Guidance for Industry

. FDA. September 8, 2025. Accessed June 3, 2026. 

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/development-therapeutic-protein-biosimilars-comparative-analytical-assessment-and-other-quality

Scientific Considerations in Demonstrating Biosimilarity to a Reference Product: Updated Recommendations for Assessing the Need for Comparative Efficacy Studies, Draft Guidance for Industry

. November, 20 2025. Accessed June 3, 2026. 

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/scientific-considerations-demonstrating-biosimilarity-reference-product-updated-recommendations

New and Revised Draft Q&As on Biosimilar Development and the BPCI Act (Revision 4)

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/new-and-revised-draft-qas-biosimilar-development-and-bpci-act-revision-4

FDA Takes Further Steps to Streamline Biosimilar Development and Make Medicines More Affordable. Press release. FDA. March, 9 2026, Accessed June 3, 2026. 

https://www.fda.gov/news-events/press-announcements/fda-takes-further-steps-streamline-biosimilar-development-and-make-medicines-more-affordable

Kimberly Salgado is head of Centre for Biosimilar Drug Development, ICON plc.

Articles

Regulatory evolution since 2024 is materially reshaping biosimilar development in the EU and US by shifting evidentiary weight from clinical comparative efficacy toward state-of-the-art analytics and PK similarity. Both EMA and FDA increasingly support tailored pathways where robust physicochemical and functional characterization can obviate confirmatory efficacy trials, while maintaining their role for complex or poorly characterized products. FDA’s 2026 Q&A revision enables greater reliance on non‑US comparators, lowering program costs and enabling global development strategies amid intensifying competition.

Changes in regulations are reducing costs, expediting approval, and increasing the market for biosimilars.