Measuring biotherapeutics with endogenous counterparts and pre-existing antibodies: an interferon case study. (April 2014)

• Record Type: Journal Article
• Authors: Myler, Heather; Felix, Tonya; Zhu, Jie; Hruska, Matt; Piccoli, Steven P
• Is Part Of: Bioanalysis. Volume 6:Number 8(2014)
• Page Start: 1113
• Page End: 1122
• Publication Date: 2014-04
• Subjects: Drugs -- Analysis -- Periodicals; 615.19005
• DOI: 10.4155/bio.14.37
• Languages: English
• ISSNs: 1757-6180

Abstract

Background: This article presents case study data demonstrating the importance of having a thorough understanding of matrix-interference in support of global clinical trials.Methods/Results: A ligand-binding assay used in the measurement of interferon lambda in human serum was transferred from the reference laboratory to a US-based comparator laboratory and then to a China-based comparator laboratory. The method was successfully validated at each laboratory, however, during cross-validation, there were notable differences, including 30–60% difference in incurred study sample results. The differences were attributed to matrix factors included in the serum pool used to prepare standards and quality controls. Newly procured serum (n = 75 individuals) was tested for assay interference. 12% contained either pre-existing antibodies (auto-antibodies) or were identified as pharmacokinetic assay outliers.Conclusion: Prescreening of serum to exclude reactive individuals resulted in successful cross-validation and the establishment of a high integrity pharmacokinetic assay in support of global clinical trials.