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. 2023 Jul 8;25(4):69.
doi: 10.1208/s12248-023-00830-5.

Neutralizing Antibody Validation Testing and Reporting Harmonization

Heather Myler  1   2 , João Pedras-Vasconcelos  3 , Todd Lester  4 , Francesca Civoli  5 , Weifeng Xu  6 , Bonnie Wu  7 , Inna Vainshtein  8 , Linlin Luo  6 , Mohamed Hassanein  9 , Susana Liu  10 , Swarna Suba Ramaswamy  11 , Johanna Mora  12 , Jason Pennucci  13 , Fred McCush  14 , Amy Lavelle  15 , Darshana Jani  16 , Angela Ambakhutwala  17 , Daniel Baltrukonis  14 , Breann Barker  18 , Rebecca Carmean  15 , Shan Chung  19 , Sheng Dai  20 , Stephen DeWall  21 , Sanjay L Dholakiya  12 , Robert Dodge  22 , Deborah Finco  23 , Haoheng Yan  24 , Amanda Hays  4 , Zheng Hu  25 , Cynthia Inzano  12 , Lynn Kamen  4 , Ching-Ha Lai  26 , Erik Meyer  27 , Robert Nelson  28 , Amrit Paudel  29 , Kelli Phillips  14 , Marie-Eve Poupart  30 , Qiang Qu  13 , Mohsen Rajabi Abhari  31 , Janka Ryding  32 , Curtis Sheldon  33 , Franklin Spriggs  34 , Dominic Warrino  35 , Yuling Wu  36 , Lin Yang  37 , Stephanie Pasas-Farmer  38
Affiliations

Neutralizing Antibody Validation Testing and Reporting Harmonization

Heather Myler et al. AAPS J. .

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.

Keywords: FDA; anti-drug antibodies (ADA); immunogenicity; neutralizing antibodies (NAb); regulatory guidance; validation.

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