Guideline for Biosimilar Drug Development in 2026

What are biosimilar drugs?

Biosimilar drugs are biological medicines developed to be highly similar to an already approved biologic drug, known as the reference product. Because biologics are large, structurally complex molecules produced in living systems, biosimilar drugs cannot be exact molecular copies in the way small-molecule generics are.

The scientific and regulatory goal of biosimilar drugs development is to demonstrate that any observed differences do not result in clinically meaningful differences in safety, purity, or potency.
 
Key takeaway: Biosimilar drugs are approved by proving similarity through analytical evidence, not by duplicating a molecule.

Regulatory momentum toward analytical evidence for biosimilar drugs

 

Regulators are changing how they evaluate biosimilar drugs. Both U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) agencies clearly signal a move toward analytically driven biosimilar approval, with increasing alignment across regions.

 

In April 2025, the EMA released a draft reflection paper (for public consultation) to explore when clinical efficacy data may be de-emphasized in favor of analytical and PK evidence. The paper does not create a formal guideline with regulatory force yet, but it signals EMA’s intent.

 

Similarly, in October 2025, the FDA released a draft guidance proposes that for many biosimilars, especially well-characterized proteins, the agency may no longer routinely require comparative clinical efficacy studies (CES) if robust analytical and pharmacokinetic data sufficiently demonstrate similarity to the reference product. The draft replaces older expectations by emphasizing comparative analytical assessment (CAA) and targeted PK data, and was published to reduce time/cost burdens on biosimilar developers.

 

Additionally, in 2025, the FDA finalized a guidance on therapeutic protein biosimilars (focused on comparative analytical studies), which further clarifies current expectations for demonstrating analytical similarity.

 

 

 

 

Interchangeability is a regulatory designation used in the United States that applies to certain biosimilar drugs.

If a biosimilar is designated as interchangeable by the FDA:

• A pharmacist may substitute it for the reference biologic without contacting the prescriber, depending on state law

• The patient should expect the same clinical outcome, even if switched back and forth

 

 

A clear trend toward regulatory harmonization

Global regulators are converging on analytical excellence as the basis for reducing clinical study requirements for biosimilar drugs. When analytical characterization is deep, orthogonal, and scientifically rigorous, the need for large comparative clinical trials can be significantly reduced without compromising regulatory confidence.

What this means for biosimilar drugs developers

 

FDA and EMA evidence requirements for biosimilar drug development in 2026 now depends primarily on analytical strength rather than clinical scale. Consequently, developers must invest early in analytical strategies capable of detecting and justifying subtle structural and functional differences. Analytical gaps that were previously compensated by clinical data now represent program-level risk, often leading to delayed timelines, additional regulatory questions, or the need for late-stage study redesigns.

 

Why biosimilar drugs development is becoming an analytical challenge in 2026

In 2025, biosimilar drugs development has shifted toward an analytically driven regulatory model. Instead of relying heavily on large clinical efficacy studies, they are placing more weight on strong analytical and pharmacokinetic evidence.. The consequences are that in 2026 scientific risk in biosimilar drugs programs has moved upstream into analytical development.

 

Read more: The 6 Most Common Analytical Gaps in Biosimilar Programs (and how to fix them)

How biosimilar drugs development works

 

This model applies to therapeutic protein biosimilar drugs intended for regulated markets such as the United States and Europe

 

Extensive characterization of the approved reference biologic is performed to establish a detailed quality target profile.

 

High-resolution analytical methods compare the biosimilar drug and reference product across critical quality attributes, including:

 

• Primary and higher-order structure
• Post-translational modifications
• Charge and size variants
• Biological and functional activity

Targeted in vitro and, when required, in vivo studies confirm that observed analytical differences do not affect biological function.

 

Pharmacokinetic and pharmacodynamic studies compare in vivo behavior between the biosimilar drug and the reference product and are often the primary clinical requirement.

 

Step 5. Limited clinical confirmation when required

Depending on molecule complexity and analytical strength, regulators may require reduced or no comparative clinical efficacy studies.

Key takeaway: Modern biosimilar drugs programs are built analytically first, clinically second.