ABSTRACT
This chapter offers conceptual and practical consideration on the process of identification of biomarker needs and on the development and application of biomarker platforms for the preclinical assessment of potential safety issues. It focuses on pharmaceutical drug discovery and early development phases, which encompass target identification and validation, compound lead optimization, and preclinical development studies. The chapter considers the use and integration of biomarker data with traditional toxicology endpoints in the development of a risk assessment recommendation. In general, the predominant preclinical applications of toxicity biomarker data include compound lead optimization, the development of a therapeutic index using pharmacodynamic markers and toxicity biomarkers, risk assessment interpretation and recommendations using biomarker data, and the identification of the relevant toxicity biomarkers and assay platforms that will be useful during in-life toxicity studies as well as clinically. Compound-induced mutagenicity and clastogenicity are significant barriers to compound development.
