Safety assessment of pharmaceuticals: examples of inadequate assessments and a mechanistic approach to assuring adequate assessment.

For a conventional organic new chemical entity (NCE) being developed as a pharmaceutical, standard regulatory safety assessment studies are required. Early in development, an NCE should undergo a safety/benefit analysis to justify further development. This analysis is made easier and more effective when comprehensive nonclinical data are available. One of the most important aspects of nonclinical toxicologic studies is to provide information on absence of potential carcinogenicity in humans. To avoid human exposures to potentially carcinogenic agents, even in early development of an NCE, the Decision Point Approach to carcinogen testing provides a useful guide to acquisition of mechanistically relevant data for risk assessment.