Nonclinical Drug Development: Pharmacology, Drug Metabolism, and Toxicology
INTRODUCTION The discovery and development of a novel therapeutic agent, whether a small organic molecule (novel chemical entity or NCE) or a macromolecule such as a protein and oligonucleotide, require scientific expertise from a number of different disciplines and an enormous amount of time and money. While humans may be the ultimate test species to ascertain the safety and efficacy of a potential new therapeutic agent, research studies in animal models are necessary to determine whether a drug candidate has a pharmacological property that might mediate a human disease process or disorder and that the test article does not have a toxicity profile that could cause adverse experiences in humans at pharmacological doses. Present estimates suggest that about 10 to 12 years and more than $1000 million or $1 billion (with this cost including the amount expended on drug candidates that “died” during development) are needed to successfully discover and develop a novel therapeutic agent. Figure 1 presents the relationship between the dollars spent and time of development. As shown, the drug discovery and preclinical phases are relatively inexpensive compared to that for the clinical and nonclinical phases of development.