Double Duty Bioassays: A Regulatory Perspective on Bispecific Antibody Bioassay Development

Bispecific product submissions to the United States Food and Drug Administration (FDA) have increased over recent years. This may likely be attributed to advanced biotechnologies, enhanced manufacturing knowledge of therapeutic antibody products, and strong scientific rationale for the development of biologics with the ability to engage more than one target. Concurrent to the development of these complex biologic products with multiple modalities comes the need to develop bioassays that are not only accurate and reproducible, but also adequately reflective of the proposed mechanism(s) of action. Well-developed bioassays are critical aspects to the characterization and control of biological products, as well as to the interpretation of clinical study results. Bispecific bioassay development presents a unique set of challenges for assay design, such as the ability to fulfill the desired performance of the assay to capture the dual activities and potential synergist effects of the molecule preferably using a single assay format, and to detect multifaceted structural changes. This presentation will discuss challenges observed and general considerations for bispecific bioassay development from a regulatory perspective.