• Yow-Ming C Wang, Vibha Jawa, and Mark Ma.
• Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation & Research, US FDA, MD 20993, USA.
• Bioanalysis. 2014 Jan 1;6(1):79-87.

AbstractWith the advent of novel technologies, considerable advances have been made in the evaluation of the relationship between PK and PD. Ligand-binding assays have been the primary assay format supporting PK and immunogenicity assessments. Critical and in-depth characterizations of the ligand-binding assay of interest can provide valuable understanding of the limitations, for interpreting PK/PD and immunogenicity results. This review illustrates key challenges with regard to understanding the relationship between anti-drug antibody and PK/PD, including confounding factors associated with the development and validation of ligand-binding assays, mechanisms by which anti-drug antibody impacts PK/PD, factors to consider during data analyses and interpretation, and a perspective on integrating immunogenicity data into the well-established quantitative modeling approach. Through recognizing these challenges, we propose some opportunities for improvements in the development and validation of fit-for-purpose bioanalytical methods.

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