ABSTRACT
SUMMARY Nonclinical studies with and without the use of animal testing methods have the purpose of limiting risks whenever a new substance is to be tested or used therapeutically in a medicinal product inhumans. Such studies shouldbedesignedandapplied strategically in such awayas to achieve early, (almost) risk-free, and ethically unproblematic transition from nonclinical testing to clinical use under economically feasible conditions. For this purpose, the legitimate interests of trial subjects, patients, pharmaceutical manufacturers (usually the sponsors), the scientific community, as well as competent regulatory authorities have to be understood and harmonized to achieve a course of action that is medically and ethically correct (with respect to animal testing and use in humans), and to adhere to legal requirements. The development of a new medicinal product is thus guided and restricted: its progress depends on the outcome of various nonclinical and clinical investigations. The sequential order, the test details and their logic, and thedurationof testingneed tobe agreedamongall parties concernedwithproductdevelopment. Chronological overlaps rather than shortcuts need to be planned carefully. As pharmaceutical developments are moving toward “personalized medicines,” it becomes clear that each new active substance is a separate entity, whose investigations have to be strategically designed. The “flowcharts” described in this chapter support the development and application of productspecific testing strategies. They provide a platform for transparent use of decision-treemethods. The “flowchart” system allows for a structured and science-based discussion among nonclinical and clinical investigators as well as between sponsor and competent authority. Each test system available can be probed in principle to determine whether or not it is required.
