The main goal in biosimilar development is to confirm biosimilarity, which means to confirm that the proposed biosimilar matches the reference medicine in terms of safety, efficacy, and quality. Therefore, physico-chemical, structural and functional characteristics, the pharmacokinetic profiles, and pharmacological effects are performed to demonstrate that the biosimilar medicine matches the reference medicine, in terms of quality/purity, safety, and efficacy/potency, demonstrating no clinically meaningful differences. This is based on the “totality of evidence concept”.1

Biosimilars are approved via stringent regulatory pathways by the same regulatory authorities, such as the European Medicines Agency (EMA), the US Food and Drug Administration (FDA), or the World Health Organization (WHO), that approve reference medicines. They are manufactured with the same quality standards that are used for reference medicines. 2,3

Stages of biosimilar development

Biosimilar development differs from development of reference medicines, which focuses on establishing and proving clinical benefit. Both approaches provide the same level of confidence with regard to safety and efficacy of the biologic.

Stages of biosimilar development

Find out more about each stage: 

Extensive physicochemical characterization to establish ‘sameness’ of the biosimilar structure to the reference molecule e.g. in terms of molecular structure.​4,5

Extensive in vitro (cell culture) testing and biological characterization to demonstrate functional comparability of the biosimilar with the reference molecule.​4,5

Robust, comparative Clinical Phase I PK/PD studies in humans to determine bioequivalence i.e. that the biosimilar and the reference medicine will work in the body the same way.​4

Clinical Phase III confirmatory safety and efficacy study conducted in a sensitive patient population to confirm that the safety and efficacy of the biosimilar matches the reference medicine.4

To learn more, download our biosimilars development brochure "From concept to reality" (PDF, 1.2 MB) 

Extrapolation: A well-established scientific principle

Extrapolation is the scientific and regulatory process of granting a clinical indication to a medicine without conducting clinical safety and efficacy study in that indication. Extrapolation is an established principle that has been applied over many years to obtain approval after major changes in the manufacturing process, changes to the formulation and/or strength or changing the mode of administration of biologics from intravenous (IV) to subcutaneous (SC).6,7,8

Sandoz is a pioneer and global leader in biosimilars and has approved biosimilars in highly regulated markets of the US, Canada, EU, Japan and Australia.9-13

Variability of biologics

A biological medicine (commonly referred to as a “biologic” or “biopharmaceutical”) is a pharmaceutical drug whose active substance is made by or extracted from living organisms, tissues, or cells.3,15

Due to inherent variability in the biologic system and the manufacturing process, any resulting biologic will display a certain degree of variability (“microheterogeneity”), even within a given batch and between different batches of the same medicine.16, 17

Companies developing biosimilar medicines develop a novel manufacturing process. The quality standards of good manufacturing practices (GMP) apply to the manufacturing of a biosimilar in the same way as for a reference biologic. Compliance with these GMP guidelines is routinely verified during GMP inspections by competent national authorities. 3, 14, 18

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  1. Cohen HP, et al. Chapter 22: Totality of evidence and the role of clinical studies in establishing biosimilarity. In: Gutka HJ, Yang H, Kakar S. (ed) Biosimilars: regulatory, clinical, and biopharmaceutical development. Springer, 2018.
  2. European Medicines Agency (EMA). Biosimilar medicines: Overview. Available from: https://www.ema.europa.eu/en/human-regulatory/overview/biosimilar-medic… [Accessed November 2021]
  3. European Medicines Agency and European Commission. Biosimilars in the EU: Information guide for healthcare professionals. 2019. Available from: Biosimilars in the EU - Information guide for healthcare professionals (europa.eu) [Accessed November 2021].
  4. McCamish, M. et al. The State of the Art in the Development of Biosimilars. Clinical Pharmacology and Therapeutics. 2012;91(3):405–17.​
  5. Kurki, P. et al. Interchangeability of biosimilars: a European perspective. BioDrugs. 2017;31(2):83-91.
  6. Weise M et al. Biosimilars: The Science of Extrapolation, Blood VOLUME 124, NUMBER 22, 2014.
  7. Rojas-Chavarro LF and de Mora F. Extrapolation: Experience gained from original biologics. Drug Discov Today. 2021;26:2003–13
  8. Tu KN, et al. Osteoporosis: a review of treatment options. P T. 2018;43:92–104.
  9. Center for Drug Evaluation and Research. Approval Letter: Omnitrope®. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021426s000_APPR… [Accessed December 2022]. ​
  10. Generics and Biosimilars Initiative. Biosimilars approved in Canada. Available from: https://www.gabionline.net/biosimilars/general/biosimilars-approved-in-… [Accessed December 2022].
  11. European Medicines Agency (EMA). Omnitrope® Summary of Product Characteristics. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Inf…  [Accessed November 2021]
  12. Pharmaceuticals and Medical Devices Agency (PMDA). PMDA Perspective: Recent Trends in the Regulation of Biopharmaceuticals. Available from: Slide 24 (pmda.go.jp) [Accessed November 2021].
  13. Australian Government. Department of Health, Therapeutic Goods Administration. Public Summary for Omnitrope® (Somatropin) 
  14. Weise M, et al. Blood. Biosimilars: what clinicians should know. 2012; 120(26):5111-1117
  15. Heads of Medicines Agencies (HMA). Co-ordination group for mutual recognition and decentralised procedures – human (CMDh). Questions & answers on biologicals, CMDh/269/2012. Rev. 2. 2020. Available at https://www.hma.eu/fileadmin/dateien/Human_Medicines/CMD_h_/Questions_A… Dh_269_2012_Rev._2_2020_02_clean_Q_A_on_biologicals.pdf; accessed November 2022.
  16. Gerrard TL, et al. Biosimilars: extrapolation of clinical use to other indications. GaBI Journal 2015;4:118–24.
  17. McCamish M and Woollett GR. Molecular "sameness" is the key guiding principle for extrapolation to multiple indications. Clin Pharmacol Ther. 2017;101:603–5.
  18. Furrow ME and Isaacson AA. Biosimilars and the Biologics Price Competition and Innovation Act (BPCIA). Practical Guidance. 2021. Available at https://kilpatricktownsend.com/en/Insights/Publications/2021/2/Biosimil…; accessed November 2022