Strategies for preclinical immunogenicity assessment of protein therapeutics.

The immunogenicity assessment of protein therapeutics has received significant attention, both from regulatory bodies and industry. With the advent of several industry white papers and the EMEA guidance on the clinical assessment of antidrug antibodies (ADAs), the immunogenicity screening framework has become better defined. Immunogenicity in many cases leads to the loss of efficacy of a drug, but can also lead to the production of severe adverse effects. A risk assessment should be conducted for every biotherapeutic under development to address the incidence rate of immunogenicity, as well as the severity of the adverse effects caused. Typically, immunogenicity is characterized by measuring the ADAs that occur in individuals exposed to a drug. Industry and academic research efforts are geared toward the assessment of potential immunogenicity in a preclinical setting, with the aim of predicting immunogenicity prior to clinical trials, and thereby reducing the attrition rate of drugs in clinical development. This article addresses the current status, strategies and challenges related to the predictive immunogenicity assessment of protein therapeutics.