From 3-Tier to adaptive immunogenicity testing strategies: recommendations from the European Bioanalysis Forum

The European Bioanalysis Forum discusses a recommended shift from the traditional 3-Tier immunogenicity testing approach to a more adaptive immunogenicity testing strategy for biotherapeutics, emphasizing clinical relevance, risk-based considerations, assay performance, and collaboration with regulatory authorities to improve the assessment of anti-drug antibodies in therapeutic contexts. The recommendations encourage transitioning toward adaptive 1-Tier or 2-Tier combined approaches tailored to the molecule context-of-use. The new strategy prioritizes the clinical impact of anti-drug antibodies over mere incidence, advocating careful consideration of assay characteristics during assay development. The European Bioanalysis Forum continues to call for published case studies, industry cooperation, and proactive dialogue with regulatory authorities to challenge the traditional 3-Tier approach.