The Implementation of the Three Rs in Regulatory Toxicity and Biosafety Assessment: The Indian Perspective

Abstract

Animal models have long served as a basis for scientific experimentation, biomedical research, drug development and testing, disease modelling and toxicity studies, as they are widely thought to provide meaningful, human-relevant predictions. However, many of these systems are resource intensive and time-consuming, have low predictive value and are associated with great social and ethical dilemmas. Often drugs appear to be effective and safe in these classical animal models, but later prove to be ineffective and/or unsafe in clinical trials. These issues have paved the way for a paradigm shift from the use of in vivo approaches, toward the ‘science of alternatives’. This has fuelled several research and regulatory initiatives, including the ban on the testing of cosmetics on animals. The new paradigm has been shifted toward increasing the relevance of the models for human predictivity and translational efficacy, and this has resulted in the recent development of many new methodologies, from 3-D bio-organoids to bioengineered ‘human-on-a-chip’ models. These improvements have the potential to significantly advance medical research globally. This paper offers a stance on the existing strategies and practices that utilise alternatives to animals, and outlines progress on the incorporation of these models into basic and applied research and education, specifically in India. It also seeks to provide a strategic roadmap to streamline the future directions for the country’s policy changes and investments. This strategic roadmap could be a useful resource to guide research institutions, industries, regulatory agencies, contract research organisations and other stakeholders in transitioning toward modern approaches to safety and risk assessment that could replace or reduce the use of animals without compromising the safety of humans or the environment.