Bioanalysis of target biomarker and PK/PD relevancy during the development of biotherapeutics.

The majority of biotherapeutic drugs act on specific targets, which may serve as biomarkers to be evaluated for target engagement and validation. Together with subsequent pathway biomarkers, these data can provide proof-of-mechanism and understanding of the biological drug affect. A major task during early development is to predict, for the first first time in human clinical trials, the starting dose and simulate the PK/PD relationship. However, determinations of the biotherapeutic drug and target concentrations are not straightforward due to temporal changes of drug-target binding and challenges in developing reliable methods to measure the free and total drug and target. Herein, the bioanalysis of the target biomarker and the biotherapeutics in the context of PK/PD relevancy during drug development is reviewed. Binding of the target to the biotherapeutic will affect target clearance and drug disposition, resulting in nonlinear PK. Reliable and specific methods are crucial for the correct PK/PD modeling and interpretation.