Biosimilars Clinical Trials | Amgen Biosimilars

Clinical Testing

Programs designed to promote quality

Our data packages provide further evidence of our strengths. Amgen generates robust and rigorous data on each of our biosimilar medicines. These data packages:1
  • Use sensitive endpoints
  • Ensure no clinically meaningful differences in:
    • Efficacy
    • Safety
    • Immunogenicity
These data are needed to demonstrate biosimilarity for regulatory approval for high quality biosimilars.

Analytical, nonclinical, and clinical data

Biosimilar development process

Biosimilar development process1,2
Once we have assessed the reference drug and established its critical quality attributes (CQAs), we design a manufacturing process for the biosimilar. Then, over several years of testing, we collect data needed to prove biosimilarity and obtain approval.
  • A comprehensive comparison of the quality attributes of the biosimilar molecule with the reference product using state-of-the-art methods supports that the products are biosimilar on a structural and functional level.1,2
  • Even with robust analytical data, the biosimilar can be approved only with additional nonclinical and clinical data.1

Biosimilar development1,3

Demonstrate no clinically meaningful differences in safety and effectiveness in one or more appropriate conditions of use for which the reference product is licensed.

Reference product development3
Demonstrate safety and effectiveness in each condition of use with adequate, well-controlled, substantial evidence for a new product.

Totality of evidence determines similarity

Proven biosimilarity requires proven science

Proven biosimilarity requires proven science1,4,5
Together, the above data make up the totality of evidence which is used to assess the level of biosimilarity.1

Clinical data

Comparative pharmacokinetic (PK)/pharmacodynamic (PD) studies

Comparative pharmacokinetic (PK)/pharmacodynamic (PD) studies
Comparative PK/PD studies use healthy volunteers or patients to collect pharmacokinetic (PK) and pharmacodynamic (PD) data in order to demonstrate similarity in drug exposure and response in the body. They are conducted in one of two ways:6,7
  • Parallel group: healthy subjects or patients receive either the biosimilar medicine or the reference biologic
  • Crossover: two groups of subjects first receive either the biosimilar or the reference product, and then the groups are switched to receive the other treatment
Comparative clinical studies
Comparative clinical studies demonstrate the biosimilar medicine has similar efficacy, safety, and immunogenicity with no clinically meaningful differences to the reference product. These studies should be performed in a population that is sensitive enough to detect clinically meaningful differences between the biosimilar and the reference product, should any exist. A comparative clinical study will demonstrate:1
  • That efficacy is neither inferior nor superior to the reference product
  • That there are no clinically meaningful differences in safety and immunogenicity
Clinical requirements for biosimilar development differ by regulatory agency. In general, PK similarity and comparative clinical studies are required. Dose-ranging or -finding studies are not typically required because the reference product’s dosing has already been established.1,8


Regulatory agencies review the totality of evidence to determine whether the biosimilar can be approved for some or all of the indications of the reference product.1

Extrapolation of indications

Regulatory guidance description of the requirements for extrapolation

References: 1. US Food and Drug Administration. Guidance for industry: scientific considerations in demonstrating biosimilarity to a reference product. Accessed October 29, 2019. 2. Conner J, Wuchterl D, Lopez M, et al. The biomanufacturing of biotechnology products. In: Shimasaki C, ed. Biotechnology Entrepreneurship: Starting, Managing, and Leading Biotech Companies. Waltham, MA: Academic Press; 2014:351-385. 3. Blauvelt A, Cohen AD, Puig L, Vender R, van der Walt J, Wu JJ. Biosimilars for psoriasis: preclinical analytical assessment to determine similarity. Br J Dermatol. 2016;174:282-286. 4. Kresse GB. Biosimilars—science, status and strategic perspective. Eur J Pharm Biopharm. 2009;72:479-486. 5. European Medicines Agency. Guideline on similar biological medicinal products. WC500176768.pdf. Accessed October 29, 2019. 6. US Federal Trade Commission. Emerging health care issues: follow-on biologic drug competition. Accessed October 29, 2019. 7. Alten R, Cronstein BN. Clinical trial development for biosimilars. Semin Arthritis Rheum. 2015;44:S2-S8. 8. European Medicines Agency. Biosimilars in the EU: information guide for healthcare professionals. Accessed October 29, 2019.