December 11, 2024
Speakers: Timothy McGovern and Todd Bourcier
Educational Levels: Advanced, Emerging

The S1BR1 addendum expanded the evaluation process for assessing the human carcinogenic risk of pharmaceuticals. The addendum introduced a weight-of-evidence (WoE) approach to determine if a two-year rat study would add value to an assessment based on an integrated review of drug target pharmacology and compound-specific toxicology. Successful implementation of this approach would ideally shift focus toward more mechanism-based carcinogenicity assessments and reduce the use of animals, while continuing to promote the safe development of new pharmaceuticals. To support successful implementation, the FDA arranged a review forum comprised of key review staff and members of the Executive Carcinogenicity Assessment Committee to discuss and provide recommendations on sponsors’ WoE submissions. This approach increases familiarity with these submissions, fosters consistency in review and regulatory decision making, and allows for tracking decisions and lessons learned from each submission. Initial experience with S1BR1 WoE submissions indicates that concordance with the sponsor’s assessments is reasonably consistent with expectations from the prospective evaluation study which supported implementation of the addendum. Sponsor submissions have varied in quality and completeness. This session will provide an overview of the WoE approach described in the ICH S1B Addendum and summarize initial experience with implementation including key strengths and deficiencies of the WoE submissions.