Chapter 6 - Reproductive and Developmental Safety Evaluation of New Pharmaceutical Compounds

Abstract

The term “Pharmaceuticals” usually implies (1) innovative small-molecule drugs, their therapeutic equivalents, or generic medicinal products; (2) innovative biopharmaceutical medicinal products of biotechnology origin and their biosimilar, follow-on biologics or biogeneric medicinal products; and (3) veterinary pharmaceuticals. This chapter outlines the identification, interpretation, and communication of potential reproductive and developmental toxicity hazard/risks that are usually characterized for new pharmaceutical compounds. These compounds if approved by appropriate regulatory body for marketing could then be prescribed as drugs for men and women of various age groups to treat or manage specific ailment(s). When prescribed to men and women of reproductive age or to women during pregnancy, the reproductive safety information included on the product label is the primary source for reproductive safety available to physicians and patients. Reproductive safety data based on actual human experiences are always considered more relevant and preferred over data from animals but for newer pharmaceuticals, such information is usually not available or is rare. The initial label information is mainly based on animal studies performed according to internationally recognized guidelines for Developmental and Reproductive Toxicity (DART) studies in animals. Performing studies to evaluate the reproductive and developmental effects of a test article in healthy men or women would be unethical as consent of the unborn (for use during pregnancy) can never be obtained. This information can only be generated in animals. The health care professionals usually know that a drug has undergone an approval process by an appropriate regulatory body such as the Food and Drug Administration in the United States but very few really know or are familiar with the extent of nonclinical testing that is undertaken by the drug's manufacturer. The nonclinical set of toxicology studies usually includes DART studies to help assure reproductive safety by identifying reproductive hazards for a New Molecular Entity or a drug. This is considered important unless the drug is intended for subjects where effects on reproductive functions are not a consideration (e.g., postmenopausal women). As the predictive value of findings observed in animal toxicity studies for use in humans is not always consistent, and at the time of drug approval, information relating to effects of an NME in pregnant women is not or rarely available, most drugs are not labeled for use during pregnancy and carry a statement “Use in pregnancy is not recommended unless the potential benefits justify the potential risks to the fetus.” The purpose of animal toxicity studies including the DART studies is to identify safety hazards and to limit the risks related to adverse or harmful effects when a new drug is used in human subjects at recommended therapeutic dosages. This information is intended to help the prescribing physician in making the best medical decision for the patient, particularly for using a drug in women of childbearing potential or in women who may become or are already pregnant.