Abstract
Background: Anti-Drug Antibody assays (ADA) are developed and constructed with biological and chemical reagents. Capture and detector reagents as well as ADA standard are considered critical for the performance’s characteristics of a bridging assay. Current literature well describes theoretical considerations to manage critical reagents (CR) life cycle management. Nevertheless, those recommendations must be completed by a pragmatic approach which have to be exemplified. Methodology: This article intends to present and describe two study cases of bioanalytical challenge coming from the practical experience of dealing with ADA CR and offers a concrete explanation of how to solve issues. Conclusion: An appropriate management of ADA CR goes through availability anticipation, characterization and by a scientific understanding process of assay and reagents inconsistency.
References
- 1. European Medicines Agency. Guideline on Immunogenicity Assessment of Therapeutic Proteins (EMEA/CHMP/BMWP/14327/2006 rev 1) (2017). https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-immunogenicity-assessment-therapeutic-proteins-revision-1 en.pdf
- 2. US FDA. Immunogenicity Testing of Therapeutic Protein Products – Developing and Validating Assays for Anti-Drug Antibody Detection (Guidance for Industry) (2019). https://www.fda.gov/regulatory-information/search-fda-guidance-documents/immunogenicity-testing-therapeutic-protein-products-developing-and-validating-assays-anti-drug
- 3. White Paper on recent issues in bioanalysis: FDA immunogenicity guidance, gene therapy, critical reagents, biomarkers and flow cytometry validation (Part 3 – recommendations on 2019 FDA immunogenicity guidance, gene therapy bioanalytical challenges, strategies for critical reagent management, biomarker assay validation, flow cytometry validation & CLSI H62). Bioanalysis 11(24), 2207–2244 (2019).
- 4. Ligand binding assay critical reagents and their stability: recommendations and best practices from the global bioanalysis consortium harmonization team. AAPS J. 16(3), 504–515 (2014).
- 5. 2018 white paper on recent issues in bioanalysis: focus on flow cytometry, gene therapy, cut points and key clarifications on bav (Part 3 – LBA/cell-based assays: immunogenicity, biomarkers and PK assays). Bioanalysis 10(24), 1973–2001 (2018).
- 6. . The Decennial Index of the white paper in bioanalysis. Bioanalysis 9(21), 1681–1704 (2017).
- 7. 2015 white paper on recent issues in bioanalysis: focus on new technologies and biomarkers (Part 3 – LBA, biomarkers and immunogenicity). Bioanalysis 7(24), 3107–3124 (2015).
- 8. EBF recommendation on practical management of critical reagents for antidrug antibody ligand-binding assays. Bioanalysis 11(19), 1787–1798 (2019).
- 9. . How to systematically evaluate immunogenicity of therapeutic proteins – regulatory considerations. New Biotechnol. 25(5), 280–286 (2009).
- 10. Strategies to determine assay format for the assessment of neutralizing antibody responses to biotherapeutics. AAPS J. 18(6), 1335–1350 (2016).
