EBF Recommendation on Practical Management of Critical Reagents for Antidrug Antibody Ligand-Binding Assays

Abstract

Immunogenicity (ISI) assays are required to measure antidrug antibodies that are generated against biotherapeutic modalities. As for any ligand-binding assays, critical reagents (CR) play a crucial role in immunogenicity assays, as the robustness and reliability of an assay are defined by the quality and long-term availability of these reagents. The current regulatory guidelines do not provide clear directions on how to implement and verify lot-to-lot changes of CR during an assay life cycle, or the acceptance criteria that should be used when implementing new lots of CR. These aspects were extensively discussed within the European Bioanalysis Forum community. In this paper, CR for immunogenicity assays are identified and the minimum requirements for introducing new lots of CR in immunogenicity assays are described.

Secondary failure: immune responses to approved protein therapeutics

“…The development of fit-for-purpose clinical assays to measure ADA and neutralizing antibody levels in patient plasma samples is no longer technologically challenging. However, real-world challenges impede the widespread clinical use of these assays and limit their utility [64][65][66], and the lack of consistent methodologies, standards, and ADA titers linked to clinical outcomes have been cited as significant challenges. Other nontrivial issues include the responsibilities for ADA testing as well as the unwillingness of insurers (or other payors) to reimburse costs associated with tests that they may view as having limited value [67].…”

A Strategic Approach to Nonclinical Immunogenicity Assessment: A Recommendation from the European Bioanalysis Forum

“…The use of such an assessment for nonclinical methods should be evaluated according to business risk and the length of time that the method will be in operation. Furthermore, changes of critical reagents [27] or minor method parameter adjustments, which may occur during analysis of animal studies with larger sample size, may be included on a case-by-case basis in the validation or as part of a partial or in-study validation to assess assay performance.…”