A Strategic Approach to Nonclinical Immunogenicity Assessment: Recommendations from the European Bioanalysis Forum
Regulatory guidelines focus on clinical requirements for evaluating anti-drug antibody (ADA) responses against biotherapeutics, but industry has disproportionately applied these to nonclinical studies. ADA responses in animals rarely predict immunogenicity in humans. The ICH S6 guidance recommends assessing immunogenicity only when there is evidence of altered pharmacodynamics, changes in exposure without pharmacodynamic markers, or immuno-mediated reactions. The European Bioanalytical Forum reached a consensus on a minimal strategic approach for nonclinical immunogenicity assessments, including when and what to assess. Additionally, they recommend an ADA assay validation and analysis strategy for when immunogenicity assessment is necessary in nonclinical toxicology studies.
Coauthor
John Cook
Senior Principal Research Scientist, Immunology, Bioanalysis and Biomarkers
Charles River