Analytical, preclinical and clinical pharmacokinetic/ pharmacodynamic (PK/PD) studies demonstrate that the active substance in the biosimilar medicine matches the reference medicine. Final confirmation of biosimilarity requires a clinical Phase III confirmatory safety and efficacy study in a sensitive indication1,2. This is different to development of reference medicines whose focus is on proving clinical effect. Both approaches provide the same level of confidence with regard to safety and efficacy of the biological medicine.
The four stages of the biosimilar development program are2:
Analytical - Extensive physicochemical characterization to establish ‘sameness’ of the biosimilar to the reference molecule e.g. in terms of molecular structure.
Preclinical - Functional studies to confirm biological function, for example mode-of-action, between the biosimilar and the reference molecule.
Clinical PK/PD - 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.
Clinical Phase III - 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.
The totality of evidence is the data package generated from the biosimilar development program to show that the biosimilar matches the reference medicine in terms of structure, function, pharmacokinetic/pharmacodynamic profile, safety and efficacy3.
Understanding biosimilar approval
To be approved for use, a biosimilar has to match the reference medicine in terms of safety and efficacy in patients, demonstrating no clinically meaningful differences. This is done using advanced analytical, preclinical and clinical studies4,5.
Biosimilars are approved via stringent regulatory pathways by the same regulatory authorities, such as the European Medicines Agency (EMA) or the Food and Drug Administration (FDA) that approve reference medicines. They are manufactured with the same quality standards that are used for reference medicines5,6.
Sandoz is the pioneer and global leader in biosimilars and has approved biosimilars in the highly-regulated markets of the US, Canada, EU, Japan and Australia.
Lemery SJ, et al. Clin Cancer Res. 2010; 16(17):4331-4338
McCamish, M and Woollett, G. Clin Pharmacol Ther. 2012; 91(3):405-417
Strand et al. Curr. Med. Res. Opin. 2017; 33(6):993-1003