Considerations from the IQ Induction Working Group in Response to Drug-Drug Interaction Guidance from Regulatory Agencies: Focus on Downregulation, CYP2C Induction, and CYP2B6 Positive Control

• DOI: 10.1124/dmd.116.074567
• Publication Date: 2017-06-24T00:55:30Z
• Authors: Niresh Hariparsad; Diane Ramsden; Jairam Palamanda; Joshua G. Dekeyser; Odette A. Fahmi; Jane R. Kenny; Heidi Einolf; Michael Mohutsky; Magalie Pardon; Y. Amy Siu; Liangfu Chen; Michael Sinz; Barry Jones; Robert Walsky; Shannon Dallas; Suresh K. Balani; George Zhang; David Buckley; Donald Tweedie
• Keywords: 0301 basic medicine; Cytochrome P-450 CYP2B6; 03 medical and health sciences; Cytochrome P-450 Enzyme System; Drug Industry; Pharmaceutical Preparations; United States Food and Drug Administration; Down-Regulation; Humans; Drug Interactions; United States; 3. Good health

The European Medicines Agency (EMA), the Pharmaceutical and Medical Devices (PMDA), Food Drug Administration (FDA) have issued guidelines for conduct of drug-drug interaction studies. To examine applicability these regulatory recommendations specifically induction, a group scientists, under auspices Metabolism Leadership Group Innovation Quality (IQ) Consortium, formed Induction Working (IWG). A team 19 from 16 39 pharmaceutical companies that are members IQ Consortium two Contract Research Organizations reviewed recommendations, focusing initially on current EMA guidelines. Questions were collated member as to which aspects require further evaluation. was then approached provide insights into their following: 1) evaluation downregulation, 2) in vitro assessment CYP2C 3) use CITCO positive control CYP2B6 induction by CAR, 4) data interpretation (a 2-fold increase mRNA evidence induction), 5) duration incubation hepatocytes with test article. IWG conducted an anonymous survey among query practices, aforementioned key points. Responses received companies. All information blinded before being shared IWG. results presented, together consensus control. Results related time course will be reported subsequent articles.