New Approach Methodologies (NAMs): Rethinking preclinical evaluation of pharmaceuticals and medical devices beyond animal models

With the expansion of research and development in pharmaceutical and medical device sector, the demand for experimental animals is predicted to increase manyfold. However, animals' suffering and mortality during scientific studies have long been a topic of controversy. In addition, the use of animals for experiments has a few other limitations, such as the need for trained labor, lengthy protocols, high expense, and most importantly, concerns about physiological relevance. "New Approach Methodologies" (NAMs) refers to a set of innovative techniques and strategies that are used in various scientific disciplines, particularly in the fields of toxicology and risk assessment. NAMs are designed to replace, refine, or reduce the use of animals in experimentation, aligning with ethical concerns and the 3Rs principles (Replacement, Reduction, Refinement). They include strategies that range from in silico to in chemico, in vitro, and ex vivo, with every strategy having respective benefits and limitations. In this chapter, we describe the state-of-the-art of various NAMs, with a note on prospects.