Redefining Regulatory Strategy with MIDD: Insights from the Draft ICH M15 Guidance

The M15 guidance consolidates years of modeling experience and regulatory review into a globally harmonized framework. Its goal is to standardize MIDD methodology and regulatory requirements, promote transparency, and accelerate innovation.

The document outlines a totality-of-evidence approach, calls for clarity in modeling context, and emphasizes transparent communication of assumptions, risks, and impact. It also introduces a structured framework to assess model credibility and regulatory influence.

The panel highlighted case studies showing how MIDD impacts regulatory decisions:

• PBPK modeling replaced certain drug-drug interaction (DDI) studies, reducing clinical burden.
• QSP modeling guided first-in-human and dose escalation strategies in oncology.
• Exposure-response analyses supported label claims and late-stage dose modifications.

These examples underscore MIDD’s ability to provide substantive and critical support in regulatory decisions in addition to the impact it has in drug development decision making

As expectations rise, early strategic planning is essential. Certara’s experts recommend five best practices:

1. Start Early – Align on key questions and modeling plans well ahead of doing the actual modeling analyses’
2. Pilot Programs – Test MIDD planning in line with the M15 framework on a focused project before scaling across the portfolio.
3. Cross-Functional Collaboration – Integrate pharmacometrics, regulatory, clinical pharmacology and clinical expertise for a joint model-informed development strategy.
4. Engage Regulators Early – Use modeling concepts and insights to foster proactive dialogue.
5. Upskill and Invest – Equip teams with tools and training to lead with confidence.

The ICH M15 guidance is more than a regulatory milestone—it’s a strategic framework for the future. It calls on drug developers to treat MIDD not as a one-off solution, but as a foundational capability that accelerates approvals, reduces risk, and delivers better outcomes.