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Receptor occupancy assessment by flow cytometry as a pharmacodynamic biomarker in biopharmaceutical development
Author(s) -
Liang Meina,
Schwickart Martin,
Schneider Amy K.,
Vainshtein Inna,
Del Nagro Christopher,
Standifer Nathan,
Roskos Lorin K.
Publication year - 2016
Publication title -
cytometry part b: clinical cytometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.646
H-Index - 61
eISSN - 1552-4957
pISSN - 1552-4949
DOI - 10.1002/cyto.b.21259
Subject(s) - biopharmaceutical , flow cytometry , biomarker , drug development , cytometry , computational biology , pharmacology , medicine , computer science , drug , chemistry , microbiology and biotechnology , biology , immunology , biochemistry
Receptor occupancy (RO) assays are designed to quantify the binding of therapeutics to their targets on the cell surface and are frequently used to generate pharmacodynamic (PD) biomarker data in nonclinical and clinical studies of biopharmaceuticals. When combined with the pharmacokinetic (PK) profile, RO data can establish PKPD relationships, which are crucial for informing dose decisions. RO is commonly measured by flow cytometry on fresh blood specimens and is subject to numerous technical and logistical challenges. To ensure that reliable and high quality results are generated from RO assays, careful assay design, key reagent characterization, data normalization/reporting, and thorough planning for implementation are of critical importance during development. In this article, the authors share their experiences and perspectives in these areas and discuss challenges and potential solutions when developing and implementing a flow cytometry‐based RO method in support of biopharmaceutical drug development. © 2015 The Authors Cytometry Part B: Clinical Cytometry Published by Wiley Periodicals, Inc.