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studies 1 (step 1) is used to determine the extent and type of non-clinical (step 2) and clinical studies 2 (step 3) required in the next step of development, always with the aim of ruling out differences in clinical performance between the biosimilar and the reference medicine. Comparability is a well-established scientific principle of regulatory science: comprehensive comparative quality studies prove that physicochemical properties and biological activity are highly similar. Comparative clinical and non-clinical studies that support the approval of a biosimilar rule out differences which may affect the medicine’s safety and efficacy.

Same pharmaceutical quality standards for all medicines

Companies developing medicines in the EU, including biosimilars, must demonstrate with a large body of data that the medicine is manufactured to agreed standards and that it is suitable for its intended clinical use (what is known as ‘pharmaceutical quality’).

The studies to prove pharmaceutical quality should provide detailed data on:

structural characterisation and other physicochemical properties

purity (traces of residues from the manufacturing process have to be controlled and must not exceed acceptable levels)

biological activity

excipients and starting materials

strength and formulation

the control of the manufacturing process (to ensure that the active substance and finished product conform with the accepted ranges for technical specifications) stability of the active substance and finished product during shelf-life under defined storage conditions

Comparability studies: the cornerstone of biosimilar development

Biosimilar development relies heavily on ‘comparability studies’ to establish biosimilarity to the reference medicine. This involves a comprehensive head-to-head comparison of the biosimilar and the reference medicine (figure 5). Comparability is conceived as a step-wise process that is tailor-made for each product (figure 5); knowledge from the initial quality comparability

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