학술논문
Neutralizing Antibody Validation Testing and Reporting Harmonization
Document Type
Original Paper
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
Source
The AAPS Journal: An Official Journal of the American Association of Pharmaceutical Scientists. 25(4)
Subject
Language
English
ISSN
1550-7416
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: