ICH adopts M12 guideline on drug interaction studies, releases draft M14 guidance on RWD

The International Council for Harmonisation (ICH) has adopted its M12 guidance, which promotes a harmonized approach in conducting and interpreting enzyme- or transporter-mediated in vitro and clinical drug-drug interaction (DDI) studies during the development of an investigational therapeutic drug. Step 4 means the document is ready for regulators to adopt in their jurisdictions.

ICH also announced the availability of the ICH M14 guidance on use of real-world data (RWD) to support drug development on 24 May.

The ICH M12 DDI guidance was released for public consultation in May 2022. (RELATED: EMA consults on ICH M12 guideline for drug-drug interaction studies, Regulatory Focus 25 July 2022)

The M12 guidance generated over 1,000 comments from 20 pharmaceutical companies; the industry said it wanted more clarity on the timing of DDI studies as well as the scope of these studies. (RELATED: ICH to adopt final guideline on drug interaction studies early next year, Regulatory Focus 27 February 2023).

The guideline “provides general recommendations for DDI evaluation due to the many possible combinations of drugs, patient populations and therapeutic contexts, but also contains specific recommendations in well-established areas.”

Currently, the regional differences in conducting these studies lead to increased drug development costs and delayed patient access to new drugs.

The revised guidance has an expanded new section on evaluating metabolism-mediated interactions for in vitro evaluation. There is new text on DDI studies for drugs as an inhibitor of Uridine 5’-diphospho- glucuronosyltransferases (UGTs), as well as DDI studies for major cytochrome P450 (CYP) enzymes.

There is also an expanded section on study planning in clinical DDI studies that addresses study populations and selecting the number of subjects, how to choose the proper dose, whether to use single or multiple doses, the choice of the route of administration, the timing of drug administrations, and the collection of samples to interpret the results of DDI studies.

ICH also released a supporting question and answer document to clarify points raised about drug interaction assessments as well as a training presentation to help with the guide’s implementation.

ICH releases Step 2 M14 guideline

ICH also announced that its M14 guideline on the principles for planning, designing and analyzing pharmacoepidemiologic studies that use RWD for assessing medicines is now available for public consultation. The guidance aims to provide a multidisciplinary guideline to harmonize post-approval non-interventional studies on drugs, vaccines, and other biologics using real-word data.

Last February, a Health Canada official announced plans to release the guidance this year at an ICH regional meeting. (RELATED: ICH targets cell and gene therapies, real-world data as topics ripe for harmonization, Regulatory Focus 23 February 2023)

The guidance provides recommendations and “high-level best practices” for conducting RWD studies.

The guidance includes a framework for generating adequate evidence using RWD, the research question to be addressed by these studies, the use of feasibility assessments to identify fit-for-purpose data to address a specific research question, and the development of a protocol to address the design and conduct of pharmacoepidemiological safety studies using subject matter experts.

ICH M12, ICH M14

ICH adopts M12 guideline on drug interaction studies, releases draft M14 guidance on RWD

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