ICH M12 DDI consultant: regulatory drug interaction support

ICH M12, finalised in 2024, harmonises how the FDA, EMA, PMDA and other regulators expect drug–drug interaction (DDI) risk to be assessed. Getting the in vitro package right first time avoids repeat studies, unnecessary clinical DDI trials and delays to your IND, CTA or marketing application. I design, oversee and interpret ICH M12-compliant DDI programmes for biotech and pharma sponsors.

What ICH M12 expects

• Reaction phenotyping: identifying the CYP and non-CYP enzymes (including UGTs) responsible for clearance, to judge victim DDI risk.
• Enzyme inhibition: reversible and time-dependent inhibition of the major CYPs, and UGTs where relevant.
• Enzyme induction: mRNA-based induction studies in human hepatocytes from multiple donors.
• Transporters: substrate and inhibitor assessment for P-gp, BCRP, OATP1B1/1B3, OAT1/3, OCT2 and MATEs.
• Metabolites: deciding which circulating metabolites also need DDI evaluation.
• Risk prediction: basic static, mechanistic static and PBPK models to decide whether, and which, clinical DDI studies are needed.

How I can help

• Gap analysis of existing DDI data against ICH M12
• Designing a fit-for-purpose in vitro DDI package for IND or CTA
• Accounting for protein binding, non-specific binding and solubility in assay design
• Selecting CROs and reviewing protocols, data and reports
• Interpreting results and recommending clinical DDI strategy
• Writing the DDI sections of IND Modules 2.6.4/2.6.5, Investigator’s Brochures and briefing books

Experience

I have more than 30 years in DMPK and have led metabolism and DDI groups in both CRO and pharma settings, including as Scientific Manager for Metabolism and DDI at Envigo. My teams provided DMPK and DDI support to four successful NDAs, including Epidiolex, and I speak regularly at scientific meetings and webinars on regulatory DDI. I also have particular expertise in cannabinoid DMPK, where DDI risk is a key regulatory focus.