ICH Announces the Availability of a Final Guideline and Questions and Answers Document on Drug Interaction Studies (M12)

https://database.ich.org/sites/default/files/ICH_M12_Step4_Q%26As_2023_0521.pdf?utm_medium=email&utm_source=govdelivery On May 22, 2024, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) announced the availability of a final guideline on Drug Interaction Studies (M12) as well as an M12 Question and Answers document (M12 Q&A). The guideline provides recommendations to promote a consistent approach in designing, conducting, and interpreting enzyme- or transporter-mediated in vitro and clinical drug-drug interaction (DDI) studies during the development of a therapeutic product. In response to questions posted during the ICH M12 comment period, the M12 Q&A was developed to provide clarity around some of the concepts related to evaluation of drug interaction covered in the M12 guideline. In clinical practice, patients are often prescribed more than one drug, which can result in a DDI. Some patients, in particular fragile older patients or patients with serious or multiple health issues, can be prescribed a large number of different drugs (i.e., polypharmacy). Hence, it is important to consider an investigational drug’s potential to interact with other drugs. While regional guidelines for investigations of DDIs have been available for decades, some differences have remained despite harmonization initiatives. This ICH guideline aims to harmonize recommendations for in vitro and clinical evaluation of DDIs. The scope of the guideline is limited to pharmacokinetic interactions, with a focus on metabolic enzyme- and transporter-mediated interactions. These aspects in general apply to the development of small chemical molecules. DDI evaluation of biologics is covered briefly, with focus on monoclonal antibodies and antibody-drug conjugates. Recommendations are 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 evaluations and DDI predictions are also covered. https://database.ich.org/sites/default/files/ICH_M12_Step4_Guideline_2024_0521_0.pdf?utm_medium=email&utm_source=govdelivery ICH’s goal is to foster development of uniform, scientifically driven, international standards to improve the efficiency of new drug development and promote public health by, among other things, preventing duplication of clinical trials and minimizing the use of animal testing. To learn more about ICH, visit the organization’s website, and to learn more about ICH’s published and working-in-progress guidelines, visit the Guideline Database. https://www.ich.org/page/ich-guidelines?utm_medium=email&utm_source=govdelivery