Complex primary cell assays: strategic tools for biosimilar comparability

The release of a recent EMA reflection paper, aligning with FDA and WHO positions, has resulted in a renewed focus on the central role of pharmacokinetic (PK) data, the primary status of analytical similarity, and the conditions under which a Comparative Efficacy Study (CES) may be waived. A CES, in the context of biosimilars, is a clinical trial designed to directly compare the therapeutic efficacy and safety of a biosimilar to its reference (originator) biologic drug.

Regulators may now be open to taking a "totality of evidence" approach, where a CES may be waived if there exists strong scientific justification to support this. For this to be the case, analytical and functional similarity must be highly robust and supported by PK and immunogenicity data.

It is increasingly recognised that CES offers limited insight into quality attribute (QA) differences between biosimilars and reference products (and can even highlight differences which are later shown to be irrelevant), with analytical data providing the critical “fingerprint-like” foundation for biosimilarity.

This webinar will examine how complex primary cell assays can be strategically leveraged to complement analytical similarity data. These assays, designed to more closely mimic patient biology, offer a powerful means of demonstrating functional similarity, particularly for biologics with complex mechanisms of action.

With complex modalities, the careful planning of each individual in vitro package now does offer the opportunity to streamline biosimilar development. We will discuss how integrating such assays into a predefined similarity assessment protocol can strengthen the overall evidence package and support regulatory confidence in the absence of CES.

Learning Objectives:

• Understand the evolving regulatory landscape for biosimilar development, including when a Comparative Efficacy Study (CES) may be waived.
• Recognise the limitations of Comparative Efficacy Studies (CES) in detecting meaningful differences between biosimilars and reference products.
• Explore the strategic role of complex primary cell assays in demonstrating functional similarity and enhancing analytical comparability for biologics with complex mechanisms of action.