Clinical Trial Design

Robustly designed clinical trials are important for regulatory approval, to inform treatment decisions, and to help instill confidence.1

Clinical studies should be robustly designed, utilizing sensitive endpoints and patient populations to accurately evaluate any potential clinically meaningful differences in efficacy, safety, and immunogenicity when compared to the reference biologic. These comprehensive designs will not only provide an important component for regulatory approval, but are intended to provide robust information to equip clinicians in making treatment decisions and to help instill patient confidence.2,3

Although clinical requirements for biosimilar development differ by regulatory agency, in general, two phases of clinical studies are required:

  1. Phase 1 study to demonstrate similar pharmacokinetics (how a medicine moves through the body) and pharmacodynamics (effect of the medicine in the body)
  2. Phase 3 pivotal study to demonstrate similar efficacy, safety, and immunogenicity to the reference biologic

Phase 1 Trials

Phase 1 trials performed in either healthy volunteers or patients are used to determine whether the pharmacokinetic and pharmacodynamic profile of the biosimilar is equivalent to the reference biologic.3,4

There are two ways to design phase 1 biosimilar clinical trials: 

  1. In a parallel group study design, enrolled healthy subjects receive either the biosimilar candidate or the reference biologic for the duration of the study

  2. In a cross-over study design, two groups of enrolled subjects first receive either the proposed biosimilar, or the reference biologic, and then are switched to receive the other treatment


The objective of the pivotal trial is to demonstrate that there are no clinically meaningful differences between the proposed biosimilar and the reference biologic in terms of efficacy, safety, and immunogenicity.3

This means that the proposed biosimilar is neither inferior nor superior to the originator biologic medicine with respect to efficacy, and that it is not worse with respect to safety or immunogenicity.1

A biosimilar clinical trial should be performed in a population that is sensitive enough to detect clinically meaningful differences between the proposed biosimilar and the reference product, if differences exist.1


Conceptual Schematic for Clinical Trial Design for Biosimilars4 

PK=pharmacokinetics;  PD=pharmacodynamics.

Amgen biosimilar clinical trials


  1. US Department of Health and Human Services. Scientific considerations in demonstrating biosimilarity to a reference product. Guidance for industry. Accessed November 23, 2016.
  2. Lai Z, La Noce A. Key design considerations on comparative clinical efficacy studies for biosimilars: adalimumab as an example. RMD Open. 2016; 2:e000154.
  3. US Federal Trade Commission. Emerging health care issues: follow-on biologic drug competition. Accessed November 23, 2016.
  4. Alten R, Cronstein BN. Clinical trial development for biosimilars. Semin Arthritis Rheum. 2015;44:S2-S8.