Chapter 28 - Preclinical Development of Nononcogenic Drugs (Small and Large Molecules)

Abstract

Preclinical or nonclinical regulatory requirements that should be considered for the development of pharmaceuticals and biopharmaceuticals have been outlined in this chapter. Preclinical development encompasses the activities that link drug discovery in the laboratory to initiation of human clinical trials. Preclinical studies are designed to identify a lead candidate from several hits; develop the best procedure for new drug scale-up; select the best formulation; determine the route, frequency, and duration of exposure; and ultimately support the intended clinical trial design. Preclinical regulatory requirements for pharmaceuticals and biopharmaceuticals can vary, but both have some common features. Rodent and nonrodent mammalian species are used to delineate the pharmacokinetic profile and general safety, as well as to identify toxicity patterns of pharmaceuticals. For biopharmaceuticals, appropriate preclinical studies should take into consideration the use of a relevant animal species since the species routinely used for preclinical safety evaluation of pharmaceuticals may not express the epitope for a biopharmaceutical. Preclinical studies identify potential target organs of toxicity and define the therapeutic index to set the initial starting doses in clinical trials. Pivotal preclinical safety studies generally require regulatory oversight as defined by US Food and Drug Administration (FDA) good laboratory practices and the International Conference on Harmonization (ICH) guidelines.