Clinical Testing

Programs designed to inspire confidence

Our data packages provide further evidence of our strengths. Amgen generates robust and rigorous data on each of our biosimilar medicines. These data packages1:

  • Use sensitive endpoints and patient populations
  • Ensure no clinically meaningful differences in:
    • Efficacy
    • Safety
    • Immunogenicity

This data is needed for approval, and importantly, equips clinicians and patients with information they need to make confident treatment decisions.

Analytical, nonclinical, and clinical data

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 similarity and obtain approval.

  • A comprehensive comparison of the attributes of the biosimilar molecule with the reference product using state-of-the-art methods ensures there are no clinically meaningful differences.1,2
  • Even with robust analytical data, the biosimilar can be approved only with additional nonclinical and clinical data.2
BioEngage
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 similarity and obtain approval.

  • A comprehensive comparison of the attributes of the biosimilar molecule with the reference product using state-of-the-art methods ensures there are no clinically meaningful differences.1,2
  • Even with robust analytical data, the biosimilar can be approved only with additional nonclinical and clinical data.2

Biosimilar development1,3

Demonstrate safety, purity, and potency in one or more appropriate conditions of use for which the reference product is licensed.

Reference product development3

Demonstrate safety and effectiveness with adequate, well-controlled, substantial evidence for a new product.

Totality of evidence determines similarity

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

Clinical data

Clinical requirements for biosimilar development differ by regulatory agency. In general, phase 1 and phase 3 trials are required.6,8 Phase 2 trials are not typically required because the reference product’s dosing has already been established.

BioEngage
Phase 1 and Phase 3 trials
Phase 1

Phase 1 trials use healthy volunteers or patients to collect pharmacokinetic (PK) and pharmacodynamic (PD) data. They are conducted in one of two ways6,7:

  • Parallel group: healthy subjects 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
Phase 3 trials

Phase 3 trials demonstrate the biosimilar medicine has similar efficacy, safety, and immunogenicity to the reference product. These trials should be performed in a population that is sensitive enough to detect clinically meaningful differences between the biosimilar and the reference product. A phase 3 trial will demonstrate2:

  • Efficacy that is neither inferior nor superior to the reference product
  • Equivalent safety and immunogenicity

Clinical requirements for biosimilar development differ by regulatory agency. In general, phase 1 and phase 3 trials are required.6,8 Phase 2 trials are not typically required because the reference product’s dosing has already been established.

References: 1. US Food and Drug Administration. Scientific Considerations in Demonstrating Biosimilarity to a Reference Product: Guidance for Industry. www.fda.gov/downloads/drugs/guidances/ucm291128.pdf. Published April 2015. Accessed April 25, 2018. 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. Kozlowski S. US FDA perspectives on biosimilar biological products. Presented at: 2014 Biotechnology Technology Summit; June 13, 2014; Rockville, MD. www.ibbr.umd.edu/sites/default/files/public_page/Kozlowski%20-%20Biomanufacturing%20Summit.pdf. Accessed April 24, 2018. 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. www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2014/10/WC500176768.pdf. Published October 23, 2014. Accessed April 25, 2018. 6. US Federal Trade Commission. Emerging Health Care Issues: Follow-On Biologic Drug Competition. www.ftc.gov/sites/default/files/documents/reports/emerging-health-­care-issues-follow-biologic-drug-competition-federal-trade-commission-report/ p083901biologicsreport.pdf. Published June 2009. Accessed April 25, 2018. 7. Alten R, Cronstein BN. Clinical trial development for biosimilars. Semin Arthritis Rheum. 2015;44:S2-S8. 8. Lai Z, La Noce A. Key design considerations on comparative clinical efficacy studies for biosimilars: adalimumab as an example. RMD Open. 2016;2:e000154. doi:10.1136/rmdopen-2015-000154

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