Overcoming disease-specific matrix effect in a clinical pharmacokinetic assay using a microfluidic immunoassay technology. (August 2017)

• Record Type: Journal Article
• Authors: Williams, Kathi; Erickson, Rich; Fischer, Saloumeh Kadkhodayan
• Is Part Of: Bioanalysis. Volume 9:Number 16(2017)
• Page Start: 1207
• Page End: 1216
• Publication Date: 2017-08
• Subjects: ELISA -- etrolizumab -- Gyros technology -- immunoassay -- matrix interference -- microfluidic -- pharmacokinetic; Drugs -- Analysis -- Periodicals; 615.19005
• DOI: 10.4155/bio-2017-0102
• Languages: English
• ISSNs: 1757-6180

Abstract

Aim: Etrolizumab, a humanized monoclonal antibody, has demonstrated clinical remission in a Phase II study of ulcerative colitis patients. In the Phase III program, a second indication, Crohn's disease was added. The pharmacokinetic ELISA used in the Phase I/II studies in normal human and ulcerative colitis sera exhibited matrix interference in the Crohn's disease population, necessitating implementation of a new technology.Methodology & results: Optimization of the original ELISA and assay redevelopment using different antibody pairs did not result in substantive improvements, necessitating implementation of an alternative technology for assay development.Conclusion: We highlight the challenges encountered with optimization/redevelopment of the original ELISA and discuss results of the new assay on the Gyros platform.