Background: In January 2020, the US FDA published two final guidelines, one entitled “In vitro Drug
Interaction Studies - Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions Guidance for Industry”
and the other entitled “Clinical Drug Interaction Studies - Cytochrome P450 Enzyme- and Transporter-Mediated
Drug Interactions Guidance for Industry”. These were updated from the 2017 draft in vitro and clinical DDI
Methods: This study is aimed to provide an analysis of the updates along with a comparison of the DDI guidelines
published by the European Medicines Agency (EMA) and Japanese Pharmaceuticals and Medical Devices Agency
(PMDA) along with the current literature.
Results: The updates were provided in the final FDA DDI guidelines and explained the rationale of those changes
based on the understanding from research and literature. Furthermore, a comparison among the FDA, EMA, and
PMDA DDI guidelines are presented in Tables 1, 2 and 3.
Conclusion: The new 2020 clinical DDI guidance from the FDA now has even higher harmonization with the
guidance (or guidelines) from the EMA and PMDA. A comparison of DDI guidance from the FDA 2017, 2020,
EMA, and PMDA on CYP and transporter based DDI, mathematical models, PBPK, and clinical evaluation of DDI
is presented in this review.