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

Area of Science:

• Biopharmaceutical Analysis
• Immunology
• Regulatory Science

Background:

• Traditional 3-Tier immunogenicity testing for biotherapeutics is widely used.
• Concerns exist regarding the efficiency and clinical relevance of the 3-Tier approach.
• The European Bioanalysis Forum (EBF) has evaluated current immunogenicity testing paradigms.

Purpose of the Study:

• To propose a shift from the traditional 3-Tier immunogenicity testing strategy to a more adaptive approach.
• To emphasize clinical relevance, risk-based considerations, and assay performance in immunogenicity testing.
• To foster collaboration with regulatory authorities for improved anti-drug antibody assessment.

Main Methods:

• Review and discussion of the traditional 3-Tier immunogenicity testing approach.
• Development of recommendations for adaptive immunogenicity testing strategies (1-Tier or 2-Tier).
• Focus on tailoring strategies to the specific biotherapeutic molecule and its context-of-use.

Main Results:

• Advocacy for adaptive immunogenicity testing strategies, including 1-Tier or 2-Tier combined approaches.
• Prioritization of the clinical impact of anti-drug antibodies (ADAs) over their mere incidence.
• Emphasis on careful consideration of assay characteristics during development.

Conclusions:

• The traditional 3-Tier approach should be challenged in favor of adaptive strategies.
• Adaptive immunogenicity testing enhances the assessment of ADAs in therapeutic contexts.
• Continued industry cooperation, case studies, and dialogue with regulatory bodies are crucial for implementing these recommendations.