New approach methodologies (NAMs) in drug safety assessment: A vision of the future

Abstract

Much progress has been made in reducing and refining animal use in toxicology testing, but progress in the use of new approach methodologies (NAMs) to replace animals is disappointing. There are many highly sophisticated NAMs available, but societal, regulatory and political barriers to their implementation remain. Change requires vision, starting with imagining a future where we are successful. Specifically, this would comprise the registration of safe and effective medicines without animal tests. How do we achieve this vision? Thinking differently, in silico methods could be used to provide a detailed assessment of target- and modality-related toxicological risks, coupled with modelling of exposure. In vitro NAMs such as microphysiological systems, microelectrode array and ion channel panels could then be employed to address hypothetical risks. Finally, the safety of first time in human trials could be assessed and assured using circulating nanobots that measure conventional clinical pathology parameters alongside new biomarkers such as circulating tissue DNA. This may seem the stuff of fantasy, but imagination is key to shaping a better future and all change starts with a vision, however far-fetched it may seem today.