Tools for Functional Assessment of Biotherapeutics

Biologically derived therapeutics, such as monoclonal antibodies (mAbs), are playing an increasingly important role in revolutionizing modern medicine for treating cancer and many autoimmune disorders. They have significantly improved health care outcomes for patients because of their superior target specificity. Because the function of the drug is impacted via multiple pathways and perturbations at various levels of the protein architecture, a detailed study of functional assessment by using orthogonal tools has become a necessary part of their characterization. In the case of biosimilars, demonstration of biological comparability to the originator is an essential component of the comparability package that the manufacturer submits to the regulatory authorities. In this article, we present many of the various tools that are routinely used for performing such functional characterization of biotherapeutic products. Traditional cell-based approaches include measurement of the antibody-dependant cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and antibody-dependent cellular phagocytosis (ADCP). More recently, approaches based on ligand binding, including fluorescence-activated cell sorting (FACS), surface plasmon resonance (SPR), and biolayer interferometry (BLI) are commonly used as well. Current understanding of the role these approaches can play in a functional assessment has been elucidated.