Back to: ICH M12 Drug-Drug Interaction Studies Final Guidance
🔔 Note: Stop playback at 1:19:32 to complete this lesson.
Presenter
Kellie Reynolds, PharmD
Director
Division of Infectious Disease Pharmacology (DIDP)
Office of Clinical Pharmacology (OCP)
Office of Translational Sciences (OTS)
Center for Drug Evaluation and Research (CDER)
US Food and Drug Administration (FDA)
Abstract
This presentation, led by Kellie Reynolds, offers a comprehensive overview of clinical drug-drug interaction (DDI) information included in the new ICH M12 final guidance. It emphasizes that DDI evaluation is tailored to the specific drug, patient population, and therapeutic context, with the ultimate goal of providing useful information for healthcare providers and patients regarding DDI liability and management. The guidance outlines various study types, including standalone, nested, index precipitant/substrate, and expected concomitant drug studies, and highlights the increasing importance of endogenous biomarkers in assessing DDI potential. Key updates include refined considerations for CYP-mediated interactions, with flexibility to use moderate inhibitors/inducers in specific scenarios, and a case-by-case approach for UGT-mediated DDIs, particularly when a drug significantly reduces a sensitive CYP3A substrate. The presentation also addresses transporter-mediated interactions, noting the current absence of index inhibitors or a classification system. Furthermore, it details the utility of mechanistic static and PBPK modeling to characterize DDI potential, predict interactions, and support extrapolation, acknowledging areas for further research to enhance the efficiency of DDI assessments.