Extrapolation
CLEAR

Extrapolation of Indications

What is Extrapolation of Indications?

  • Indication extrapolation means that a proposed biosimilar product may be licensed in one or more additional conditions for which the reference product is licensed, but for which the biosimilar itself has not been studied in clinical trials1,2

Regulatory Guidance Describes the Requirements for Extrapolation1,2

  • While extrapolation is not automatic, it may be accepted provided the totality of evidence coupled with scientific justification and knowledge of the reference product can address any identified differences1,2
1
Is the mechanism of action expected to differ across indications?

Example of data considered for extrapolation

Functional similarity is demonstrated in all mechanisms of action
ADCC, antibody-dependent cell-mediated cytotoxicity; CDC, complement-dependent cytotoxicity Data are for illustrative purposes only and do not represent actual data for a biologic medicinal product
2
Do the pharmacokinetics and pharmacodynamics vary across patient populations?

Example analysis of data

Steady state trough concentration of the reference product is similar across indications
3
Is the immunogenicity expected to vary in different patient populations?

Example analysis of data

Immunogenicity remains consistent between a biosimilar and its reference product in different conditions of use
ADA, anti-drug antibody; RP, reference product
Data are for illustrative purposes only and do not represent actual data for a biologic medicinal product
4
Are there differences in expected toxicities in different indications and patient populations?

Example analysis of data

Toxicities of the reference product are similar across indications
AE, adverse event
Data are for illustrative purposes only and do not represent actual data for a biologic medicinal product
Indication extrapolation is an essential biosimilar regulatory concept that reduces or eliminates the requirement to study a proposed biosimilar with clinical trials in every indication of the reference product3

References: 1. FDA. Scientific considerations in demonstrating biosimilarity to a reference product. Guidance for industry, 2015. Available at: https://www.fda.gov/downloads/drugs/guidances/ucm291128.pdf; 2. EMA. Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues, 2015. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2015/01/WC500180219.pdf; 3. Tesser JRP, et al. Biologics: Targets and Therapy 2017:11 5–11. All links accessed March 2018.

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