Author:
Myler Heather,Pedras-Vasconcelos João,Lester Todd,Civoli Francesca,Xu Weifeng,Wu Bonnie,Vainshtein Inna,Luo Linlin,Hassanein Mohamed,Liu Susana,Ramaswamy Swarna Suba,Mora Johanna,Pennucci Jason,McCush Fred,Lavelle Amy,Jani Darshana,Ambakhutwala Angela,Baltrukonis Daniel,Barker Breann,Carmean Rebecca,Chung Shan,Dai Sheng,DeWall Stephen,Dholakiya Sanjay L.,Dodge Robert,Finco Deborah,Yan Haoheng,Hays Amanda,Hu Zheng,Inzano Cynthia,Kamen Lynn,Lai Ching-Ha,Meyer Erik,Nelson Robert,Paudel Amrit,Phillips Kelli,Poupart Marie-Eve,Qu Qiang,Abhari Mohsen Rajabi,Ryding Janka,Sheldon Curtis,Spriggs Franklin,Warrino Dominic,Wu Yuling,Yang Lin,Pasas-Farmer Stephanie
Abstract
Abstract
Evolving immunogenicity assay performance expectations and a lack of harmonized neutralizing antibody validation testing and reporting tools have resulted in significant time spent by health authorities and sponsors on resolving filing queries. A team of experts within the American Association of Pharmaceutical Scientists’ Therapeutic Product Immunogenicity Community across industry and the Food and Drug Administration addressed challenges unique to cell-based and non-cell-based neutralizing antibody assays. Harmonization of validation expectations and data reporting will facilitate filings to health authorities and are described in this manuscript. This team provides validation testing and reporting strategies and tools for the following assessments: (1) format selection; (2) cut point; (3) assay acceptance criteria; (4) control precision; (5) sensitivity including positive control selection and performance tracking; (6) negative control selection; (7) selectivity/specificity including matrix interference, hemolysis, lipemia, bilirubin, concomitant medications, and structurally similar analytes; (8) drug tolerance; (9) target tolerance; (10) sample stability; and (11) assay robustness.
Graphical Abstract
Publisher
Springer Science and Business Media LLC
Reference60 articles.
1. Mire-Sluis AR, Barrett YC, Devanarayan V, Koren E, Liu H, Maia M, et al. Recommendations for the design and optimization of immunoassays used in the detection of host antibodies against biotechnology products. J Immunol Methods. 2004;289(1–2):1–16.
2. Koren E, Smith HW, Shores E, Shankar G, Finco-Kent D, Rup B, et al. Recommendations on risk-based strategies for detection and characterization of antibodies against biotechnology products. J Immunol Methods. 2008;333(1–2):1–9.
3. Draft Guidance for Industry. Immunogenicity assessment for therapeutic protein products. US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER); 2013.
4. Assay Development and Validation for Immunogenicity Testing of Therapeutic Protein Products Guidance for Industry, Draft Guidance. US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Devices and Radiological Health (CDRH). 2016.
5. Immunogenicity Testing of Therapeutic Protein Products —Developing and Validating Assays for Anti-Drug Antibody Detection. US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER); 2019.