Proposal for a new protein therapeutic immunogenicity titer assay cutpoint. (December 2011)

• Record Type: Journal Article
• Authors: Wakshull, Eric; Hendricks, Robert; Amaya, Caroline; Coleman, Daniel
• Is Part Of: Bioanalysis. Volume 3:Number 23(2011)
• Page Start: 2627
• Page End: 2636
• Publication Date: 2011-12
• Subjects: Drugs -- Analysis -- Periodicals; 615.19005
• DOI: 10.4155/bio.11.273
• Languages: English
• ISSNs: 1757-6180

Abstract

Background: Generally, immunogenicity assessment strategies follow this assay triage schema: screen→confirm→titer. Each requires the determination of a threshold value (cutpoint) for decision making. No guidance documents exist for the determination of a specific titration assay cutpoint. The default practice is to use the screening assay cutpoint, frequently leading to controls or samples not reaching this cutpoint. We propose a method for determination of a titration cutpoint based upon the variance of the negative-control sample.Results: Positive-control samples that did not cross a screening cutpoint did cross the titer cutpoint, albeit generating slightly lower titer values.Conclusion: Our approach is consistent with the statistical methods currently recommended for the screening and confirmatory assay cutpoints and is operationally simple and efficient.