Drug development today is hindered by unreliable preclinical models, leading to high failure rates, escalating costs, and a substantial burden of human ill-health, due to adverse effects of prescription drugs and inadequate treatment options for many major diseases.

Significant progress has now been made in developing human-relevant New Approach Methodologies (NAMs) demonstrating predictive power that either matches or exceeds that of animal studies. These advances were discussed and highlighted at a recent Royal Society Science+ meeting titled “A human focus for 21st century life sciences“.

Numerous participants at the meeting described devising human NAMs that have enabled the development of medicines with equal or greater efficacy and safety than animal studies. An important insight emerged: while animal studies have reached a ceiling in their ability to predict human outcomes, NAMs offer significant potential for continuous improvement through evolving technology. It was agreed that a realistic and achievable goal is to develop and implement human NAM-based workflows that can replace animal studies in many areas, thereby improving the efficiency and safety of drug development. Moreover, integrating in vitro and advanced human based AI driven in silico NAMs will provide a robust foundation for next generation medicines with improved safety and efficacy. Additionally, implementing pre-emptive pharmacogenomics will further enhance the safety of marketed drugs.

The use of NAMs outside the regulatory arena, such as in academia and investigative toxicology can and must be prioritised. Funding bodies should invest in NAMs in preference to animals, and compliance with the UK’s Animals (Scientific Procedures) Act 1986 must be enforced regarding the use of available ‘alternatives’, with a much greater focus on avoidance of animal use. We need to generate evidence to support claims about NAMs, benchmarking against human data where possible. Moving forward with NAMs also requires a simple, fast and robust validation process, as well as the synthesis of evidence (e.g. using systematic review methods) to evaluate what works and what does not. Much can be learned from the cosmetics industry which has already switched to NAMs, many of which have benefitted the pharmaceutical and industrial chemical sectors for decades, and improved collaboration could be reciprocally beneficial. We now need to build major international and cross-disciplinary partnerships, involve clinicians, policy makers, regulators, social scientists, philosophers and scientists in academia and industry, and engage with and secure support from the public and relevant stakeholder groups.