Application of toxicogenomic tools in the drug research and development process.

The cost for the development of new active and safe drugs is higher than ever and continues to increase. At the same time, both the pharmaceutical industry and the Regulatory Authorities are, despite the increasing effort to develop safer drugs, concerned by the risk of unexpected side effects observed in the late steps of the development of new drugs, either in late clinical development or after marketing approval. Then, the early knowledge of any potential toxic effect of a new drug is a key issue to allow adequate decision making. This means that current approaches based on the determination of the No-Adverse-Effect-Level and the Human-Equivalent-Dose are far from being perfect, and fail mainly to detect toxic phenomena of low intensity and/or low frequency. To improve the predictability of the existing experimental models, Toxicogenomics could be included into the in vitro candidate-selection steps and/or during the regulatory preclinical (or clinical) studies. In this communication, the authors present an example of the use of Toxicogenomic data to support decision making when selecting a new candidate to regulatory development. The authors also present a second example of integration of Toxicogenomics with the animal regulatory studies within the preclinical development of a new drug.