Recent Advances in Computational Toxicology and Regulatory Applications
Joseph F. Contrera, Ph.D. and Edwin J. Matthews, Ph.D., Center for Drug Evaluation and Research, Office of Testing and Research, Food and Drug Administration, Rockville, MD 20857
There is an urgent and growing need to develop and apply better, more efficient and scientifically defensible methods to meet regulatory mandates, prioritize research and reduce unnecessary testing and animal use. CDER is a unique resource of scientific information from both clinical and animal studies that has applicability beyond the area of pharmaceuticals. Toxicology and clinical adverse event databases have been created at CDER and the challenge now is developing effective ways to convert this information into useful knowledge to advance the science of risk and hazard assessment. Computational toxicology offers a means of rapidly analyzing large databases and identifying relationships and patterns which are especially useful to support regulatory and product discovery decisions. Computational toxicology software modules to evaluate carcinogenic potential were developed and validated at the CDER Office of Testing and Research under a Cooperative Research and Development Agreement, and others are in development. Computational toxicology modules operate as "virtual experts" assessing the potential toxicological properties of compounds by evaluating their degree of similarity to compounds with known chemical, physical and biological properties in the CDER database. As a result of collaboration with CFSAN, computational toxicology software was developed and is being used to support regulatory decisions related to new FDAMA requirements for food contact substances. At CDER, computational toxicology is being used to support regulatory decisions on the necessity, nature and extent of testing for excipients, contaminants or degredants that are identified late in the NDA process. The knowledge derived from the extensive resource of scientific information from both clinical and animal studies at CDER is being applied to improve the scientific basis of regulatory decisions and to facilitate the development of safe products.