Guideline for Designing and Interpreting DDI Studies

“This guideline provides recommendations for designing, conducting, and interpreting enzyme- or transporter-mediated Drug-drug Interaction (DDI) studies during the development of therapeutic products. Key points include:

1. Guideline Overview:

• Published by ICH on 21-May-2024.
• Adopted by the European Union on 30-May-2024 (effective 30-Nov-2024) and by the US FDA on 02-Aug-2024

1. Evaluating DDI Potential:

• Investigational drugs should be evaluated both as an object (affected by other drugs) and as a precipitant (affecting other drugs).
• The primary elimination routes of the investigational drug must be identified.

1. In Vitro Studies:

• Before clinical phases, in vitro data on the drug as a substrate of metabolic enzymes should be obtained to assess metabolic stability.
• Data on the investigational drug’s effect as a precipitant on major cytochrome P450 (CYP) enzymes and transporters should also be gathered.

1. Clinical DDI Studies:

• Clinical studies should follow mechanistic knowledge and provide recommendations for managing DDIs.
• Study design and data analysis must be justified based on DDI mechanisms and pharmacokinetic properties.

1. DDI Management:

• Risk assessment should guide DDI prevention and risk minimization strategies.
• Management should ensure substrate drug concentrations stay within the no-effect boundaries.

Source:https://www.ich.org/news/ich-m12-guideline-reaches-step-4-ich-process##~https://database.ich.org/sites/default/files/ICH_M12_Step4_Guideline_2024_0521_0.pdf##~https://www.ema.europa.eu/en/documents/scientific-guideline/ich-m12-guideline-drug-interaction-studies-step-5_en.pdf##~https://www.ema.europa.eu/en/ich-m12-drug-interaction-studies-scientific-guideline##~https://www.fda.gov/media/161199/download##~https://www.regulations.gov/docket/FDA-2022-D-1527/document##~https://www.fda.gov/regulatory-information/search-fda-guidance-documents/m12-drug-interaction-studies

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