Recent discussions and proposals on challenging the 3-tier immunogenicity testing strategies from the European bioanalysis forum.

Abstract

The European Bioanalysis Forum, in discussions with cross-industry experts from pharmaceutical, biotech, and contract research organizations, is continuing the challenge of the traditional 3-Tier immunogenicity testing strategy, proposing a simpler, context-driven 1-Tier approach, a recent paradigm shift that emphasizes clinical relevance and the impact of anti-drug antibodies over mere incidence. In a workshop at the 17^th annual Open Symposium, the meeting highlighted using signal-to-noise ratios to assess low-level ADA responses and addressed challenges such as nonspecific binding and assay reliability. Participants debated the need for continued confirmatory testing, and that it should be performed on a case-by-case basis. The shift aims to improve clinical testing strategies while reducing complexity, promoting data-driven decisions. Case studies, particularly from high-risk molecules, will guide implementation. Overall, there's strong support for the 1-Tier approach, but its success depends on robust data, industry collaboration, and regulatory approval.