Bioanalysis. 2025 May 13:1-12. doi: 10.1080/17576180.2025.2501934. Online ahead of print.
ABSTRACT
Assessing the performance of an immunogenicity assay before using it to support vaccine clinical trials is mandatory. Further validation of assay performance is even requested to support Phase III studies. While assay validation requires adherence to predefined acceptance criteria, there is no universal stringency level for earlier phases of assay development. Setting scientifically sound criteria for success is about finding the right balance between unavoidable assay limitations and ensuring the assay is fit-for-purpose. In this paper, we focus on the evaluation of linearity for immunogenicity assays and its use as surrogate for accuracy evaluation in the absence of reference material. We propose a simple method for evaluating assay linearity and understanding the impact of a linearity deviation on the evaluation of the response increase in clinical trial. Assessment is reliable in absence of known concentration samples, unlike methods in industry guidance, making the proposed method more versatile. Method is illustrated by two case studies, representative of the assays used in the vaccine field. Making the link between assay linearity and clinical endpoints provides a simple and clear framework to support the definition of assay validation criteria, applicable to a variety of immunogenicity assays.
PMID:40357562 | DOI:10.1080/17576180.2025.2501934
