ABSTRACT
Reporting of unwanted immunogenicity to biotherapeutics is a regulatory expectation. Currently, the practice is to use a “risk-based approach” with the goal of minimizing any safety consequences due to an immune response. In this section, we address the factors to be considered when conducting a risk assessment and categorization of the risk based on safety sequelae and, which in turn, drive the monitoring and testing strategy for antidrug antibodies (ADAs). This section also discusses aspects of the assays used to monitor for antidrug antibodies: in particular, generation of the positive control, cut point setting, and other aspects of assay validation. This section also discusses additional characterization that could be done based on risk: neutralizing antibodies, isotyping, and epitope mapping. The section then concludes with some considerations for the interpretation of ADA, data including integration of PK and PD data to understand the clinical relevance and impact of the antidrug antibodies.
