Applications of Toxicogenomics to Nonclinical Drug Development: Regulatory Science Considerations

  • Frank D. Sistare
  • Joseph J. DeGeorge
Part of the Methods in Molecular Biology™ book series (MIMB, volume 460)


Scientists in the pharmaceutical industry have ready access to samples from animal toxicology studies carefully designed to test the safety characteristics of a steady pipeline of agents advancing toward clinical testing. Applications of toxicogenomics to the evaluation of compounds could best be realized if this promising technology could be implemented in these studies fully anchored in the traditional study end points currently used to characterize phenotypic outcome and to support the safe conduct of clinical testing. Regulatory authorities worldwide have declared their support for toxicogenomics and related technological tools to positively impact drug development, and guidance has been published. However, applications of exploratory “omics” technologies to compounds undergoing safety testing remain inhibited due to two core data submission responsibility implications and ambiguities: (1) constraints arising from continual literature surveillance and data reanalysis burdens, under the shadow of looming subsequent reporting requirements to regulatory authorities as gene expression end points loosely linked to safety gain attention in the published literature, and (2) ambiguities in interpretation of validation stature remain between exploratory, probable valid, and known valid safety biomarkers. A proposal is offered to address these regulatory implementation barriers to open access for exploring this technology in prospective drug development animal toxicology studies.

Key Words

biomarker critical path drug development drug safety testing genomics guidance investigative toxicology lead optimization metabolomics proteomics qualification regulation toxicogenomics validation 


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Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Frank D. Sistare
    • 1
  • Joseph J. DeGeorge
    • 1
  1. 1.Laboratory Sciences and Investigative Toxicology, Merck & Co Inc.West Point

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