Revisiting ICH S7A after 25 years: Outcomes of a multi-stakeholder workshop and strategic pillars for modernizing...

The International Council for Harmonization (ICH) S7A guideline on safety pharmacology studies, finalized in 2000, has been pivotal in protecting clinical trial participants and patients from adverse effects of pharmaceuticals. Over the past 25 years, scientific advances, evolving drug development paradigms, and increasing diversity in therapeutic modalities have substantially changed the landscape in which safety pharmacology is applied. In parallel, technological innovations with the emergence of New Approach Methodologies, have expanded opportunities to enhance human-relevant risk assessment and reduce reliance on animal testing. To explore priorities for modernizing the guideline, a multi-stakeholder workshop was convened in Brussels in February 2026, bringing together representatives from industry, trade associations, regulatory agencies, contract research organizations, and non-governmental organizations. Discussions focused on identifying strategic scientific pillars that could inform an ICH S7A revision. Key themes included adoption of a modality- and technology-agnostic framework, greater integration of secondary pharmacology, use of state-of-the-art functional in vivo approaches, application of weight-of-evidence decision frameworks, and clearer interpretation of functional findings, including the concept of adversity. Collectively, these discussions support the development of a modernized, risk-based framework for safety pharmacology that maintains robust protection of human subjects while enabling innovation, global regulatory harmonization, and implementation of the 3Rs principles.