USA – In Vitro Drug Interaction Studies — Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions

This final guidance is intended to help drug developers plan and evaluate studies to determine the drug-drug interaction (DDI) potential of an investigational drug product. The final guidance focuses on in vitro approaches to evaluate the interaction potential between investigational drugs with cytochrome P450 enzymes (CYPs) and transporters as well as how in vitro results can inform future clinical DDI studies. The appendices of this guidance include considerations when choosing in vitro experimental systems, key issues regarding in vitro experimental conditions, and more detailed explanations regarding model-based DDI prediction strategies. See section VIII for a list of terms used in this guidance and their definitions. Note that at this time, the in vitro methods to evaluate the induction of P-gp and other transporters are not well established; therefore, recommendations for the in vitro evaluation of investigational drugs as transporter inducers are not provided.

If an in vitro assessment suggests that the sponsor should conduct a clinical DDI study, the
sponsor should refer to the January 2020 final FDA guidance for industry entitled Clinical Drug Interaction Studies —Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions. Together, these two final guidances describe a systematic, risk-based approach to assessing the DDI potential of investigational drugs and making recommendations to mitigate DDIs…