Opportunities and insights from pharmaceutical companies on the current use of new approach methodologies in nonclinical safety assessment
Jacintha Shenton, Imein Bousnina, Michael Oropallo, Rhiannon David, Lucinda Weir, Thomas K. Baker, Helen-Marie Dunmore, Rémi Villenave, Mary McElroy, Betty Pettersen, Tushar G. Kokate, Claudette L. Fuller, Kimberly A. Homan, Eloïse Hudry, Charles A. Wood, Sam Gunter
Abstract
• Scientifically justified NAM-based regulatory submissions are accepted globally. • Key justifications are no relevant species, prior experience with the target, and disease severity. • Opportunity exists to scientifically justify NAM-based approaches in broader settings. • Knowledge sharing on suitable scenarios for NAM-based filings is a general need. • Updated regulatory guidance (e.g., ICH S6) would enable increased application and adoption. Sharing New Approach Methodology (NAM)-based regulatory experiences is crucial for improving human risk assessment and reducing animal use in drug safety testing. To foster broader adoption, the Biotechnology Innovation Organization surveyed companies about NAM usage and collected case studies showcasing NAM-based regulatory filings for biotherapeutics, where NAMs replaced large animal studies for safety assessment. These scientifically justified approaches were generally accepted by global health authorities, particularly in the context of species relevance limitations, prior target modulation experience, and/or when addressing severe disease. Despite successes with NAM-based global regulatory filings, there are concerns from companies about global regulatory harmonization and clinical translatability. NAMs have the potential for greater uptake with enhanced guidance and industry–regulatory agency collaboration being key to their adoption.