title: Immunogenicity and PK/PD evaluation in biotherapeutic drug development: scientific considerations for bioanalytical methods and data analysis.
abstract: With 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.
authors.affiliation: Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation & Research, US FDA, MD 20993, USA.
authors.forename: Yow-Ming C
authors.initials: YM
authors.lastname: Wang
authors.forename: Vibha
authors.initials: V
authors.lastname: Jawa
authors.forename: Mark
authors.initials: M
authors.lastname: Ma
mesh_terms: D000818:Animals; D001681:Biological Assay / Q000592:standards; D001688:Biological Products / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D018796:Immunoconjugates / Q000493:pharmacokinetics / Q000494:pharmacology*; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007155:Immunologic Factors / Q000493:pharmacokinetics / Q000494:pharmacology*; D017452:Receptors, IgG / Q000276:immunology; D014614:Vaccines, Synthetic / Q000494:pharmacology
chemical_list: D001688:Biological Products; D018796:Immunoconjugates; D007140:Immunoglobulin Fab Fragments; D007155:Immunologic Factors; D017452:Receptors, IgG; D014614:Vaccines, Synthetic