ICH M12 on drug interaction studies - Scientific guideline
HumanScientific guidelines
This guideline provides recommendations to promote a consistent approach in designing, conducting, and interpreting enzyme- or transporter-mediated in vitro and clinical pharmacokinetic drug-drug interaction (DDI) studies during the development of a therapeutic product. These aspects in general apply to the development of small chemical molecules. DDI evaluation of biologics is only covered briefly, with focus on monoclonal antibodies and antibody-drug conjugates. Guidance is provided on how to investigate interactions mediated by inhibition or induction of enzymes or transporters, both in vitro and in vivo, and on how to translate the results to appropriate treatment recommendations.
The guideline also includes recommendations on how to address metabolite-mediated interactions. The use of model-based data evaluation and DDI predictions are also covered.
On the date of its coming into effect, ICH M12 will supersede the EMA Guideline on the investigation of drug interactions – Revision 1. Of particular note, ICH M12, unlike the existing EMA guideline, does not address drug interactions in the gastro-intestinal tract to the same extent. This will be addressed by the development of accompanying EMA guidance, anticipated to take the form of a Questions and Answers document.
Keywords: Interaction, metabolism, inhibition, induction, transport, enzyme, transport protein, transporter, absorption, physiologically based pharmacokinetic (PBPK), DDI; drug-drug interactions; pharmacokinetics; PK