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Re-thinking the current paradigm for clinical immunogenicity assessment: an update from the discussion in the
Joanne Goodman1, Kyra J Cowan2, Michaela Golob3
1Bioanalytical Services, Celerion, Lincoln, NE 68502, USA employed by AstraZeneca, Cambridge, CB21 6GH, United Kingdom during the writing of the manuscript.
Bioanalysis
|August 9, 2024
Summary
Regulatory guidance for biotherapeutic immunogenicity testing is evolving. A new paradigm proposes treating immunogenicity as a pharmacodynamic biomarker, focusing resources on patient-relevant strategies based on risk assessment and context of use.
Area of Science:
- Biopharmaceutical Development
- Immunology
- Regulatory Science
Background:
- Immunogenicity testing guidelines evolved following adverse events with erythropoietin.
- Current practices often apply high-risk molecule thinking to all biotherapeutics, irrespective of risk.
- Over 20 years of experience highlight limitations in the traditional immunogenicity testing paradigm.
Purpose of the Study:
- To challenge the existing immunogenicity testing paradigm based on accumulated industry experience.
- To propose a new framework for immunogenicity assessment and testing strategies.
- To advocate for a context-of-use-driven approach to biotherapeutic immunogenicity.
Main Methods:
- A European Bioanalysis Forum Focus Workshop in September 2023.
- Discussion and analysis of 20+ years of immunogenicity strategies and data.
- Development of recommendations for a revised immunogenicity testing paradigm.
Main Results:
- The current multi-tiered testing paradigm was challenged.
- A shift towards treating immunogenicity as a pharmacodynamic biomarker was proposed.
- Recommendations emphasize risk assessment and context of use for efficient resource allocation.
Conclusions:
- A new paradigm for immunogenicity testing is needed, moving beyond a one-size-fits-all approach.
- Context-specific immunogenicity testing strategies are crucial for patient benefit.
- Implementing informative, risk-based testing will optimize biotherapeutic development and monitoring.
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