FDA says the guidances, which will replace 2012 draft guidance entitled “Drug Interaction Studies – Study Design, Data Analysis, Implications for Dosing, and Labeling Recommendations,” reflect the agency’s efforts to help drug developers design DDI studies that provide meaningful clinical information on how to manage risks when a patient is taking more than one medication. “These complementary guidances have been updated to reflect our current thinking and create some alignment among international regulatory agencies, in particular with the European Medicines Agency and Japan’s Pharmaceutical and Medical Devices Agency,” Issam Zineh, director of the Office of Clinical Pharmacology at FDA, said. Clinical Drug Interaction Studies In this 32-page draft guidance document, FDA spells out its recommendations on the timing of clinical DDI studies, the design and conduct of such studies and the reporting and interpreting of such study results, as well as labeling recommendations. “After conducting in vitro drug metabolism and drug transporter studies, sponsors should determine the need for and timing of clinical DDI studies with respect to other studies in their clinical development program,” the draft says. In terms of the types of DDI studies, FDA explains prospective studies and retrospective evaluations, DDI studies with index perpetrators and index substrates, DDI studies with expected concomitant drugs and in silico DDI studies. In Vitro Metabolism- and Transporter-Mediated DDI Studies In this 47-page draft guidance document, FDA focuses on in vitro approaches to investigating interaction potential between investigational drugs that involve metabolizing enzymes and/or transporters. It also discusses how in vitro results can help inform future clinical DDI studies. In subsections of the draft, FDA explains the evaluation of metabolism-mediated drug interactions, transporter-mediated drug interactions, DDI potential of metabolites and labeling recommendations. Comments on both draft guidances are due by 28 January 2018. More Information On RAPS
In Vitro Metabolism- and Transporter-Mediated Drug-Drug Interaction Studies Guidance for Industry