EMA ICH M12 on drug interaction studies (Draft Guidance)

Draft Guidance

July 2022

This guideline provides recommendation 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.

Keywords: Interaction, metabolism, inhibition, induction, transport, enzyme, transport protein, transporter, absorption, physiologically based pharmacokinetic (PBPK), DDI; drug-drug interactions; pharmacokinetics; PK

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