Chapter 8 - Reproductive and developmental safety evaluation of new pharmaceutical compounds

Abstract

This chapter discusses reproductive and developmental safety evaluation of new pharmaceutical compounds. The term “pharmaceuticals” usually implies: innovative small molecules, their therapeutically equivalent or generic medicinal products; Innovative biopharmaceuticals, medicinal products of biotechnology origin and their biosimilar, follow-on biologics or biogeneric medicinal products; and veterinary pharmaceuticals. An overview of human pharmaceutical development is discussed with respect to both innovator (small and large molecule) and generic (or biosimilar) pharmaceutical compounds intended for human use. The drug development process for a new, innovator compound (a small molecule or a biotherapeutic drug product) is a long and expensive undertaking in the USA. Recent data from Centers for Disease Control (CDC, 2009) suggests that about 120,000 babies (1 in 33) in the USA are born each year with birth defects, and that birth defects are the leading cause of death during the first year of life (Mathews and MacDorman, 2008). The fertility study is generally performed in the rodent, but can be evaluated in rabbits or non-human primates (NHPs). The generic drug approval process has been reviewed for scientific issues associated with the approval process. Key differentiating features include higher target (receptor or epitope) specificity in humans for biotherapeutics and limited cross reactivity for traditional toxicology species (rat and rabbit) used for evaluating effects on reproduction and development. The system of using pregnancy categories has not changed in the USA since being established in 1979. The need for in vitro tests for reproductive and developmental toxicity was identified as early as the 1970s.