On 30 May 2025, VPH presented its formal comments and suggestions on the European Medicines Agency's (EMA) proposed guideline for assessing and reporting mechanistic models in the context of model informed drug development (EMA 2025).
In its comments to the EMA's concept paper (EMA/5875/2025), VPH supported the EMA's Modelling and Working Party (MWP) for this proactive step, which aligns with the MWP's 2025-2027 workplan and acknowledges the need to advance mechanistic modelling across the EU regulatory network. VPH expresses strong endorsement for the EMA's initiative, viewing it as a crucial step in advancing the use of computational modelling within regulatory science framework. Of specific note, prof. Liesbet Geris, VPH Executive Director (University of Ku Leuven, U. Liege), joining with prof. Francesco Pappalardo (University of Catania) and prof. Marco Viceconti (University of Bologna) of the VPH community, called for a broader scope for the guideline, suggesting the explicit inclusion of model types such as agent-based, multi-physics and multi-scale models, beyond those initially (PBPK, QSP) listed.
VPH fully agrees with the EMA's problem statement regarding the crucial need for regulators to confidently assess and quantify risks associated with decisions based on mechanistic models, recognizing Uncertainty Quantification (UQ) of integrated evidences from multiple sources, as a critical pillar for advancing regulatory science. VPH highlighted its active engagement with colleagues across pharmaceutical and devices sectors, regulatory geographies (EMA, FDA), and standardisation bodies (ASME, ISO). Through this, VPH expressed its commitment to share collective learnings and latest advancements to support the guideline authors, to best address the UQ needs.
Furthermore, VPH highlighted the importance of virtual populations and digital twins in enhancing risk assessment and supporting drug development for specific patient groups, while also emphasising the need for robust uncertainty quantification of computational models. To this end, VPH expressed its readiness to actively participate in future stakeholder outreach and consultation events, committing to gather necessary feedback and scientific evidence to assist both developers and regulators.
To conclude, VPH offered it’s support the EMA’s vision to consider Computational Modelling and Simulation (CM&S) technology as a key enabler for Model Informed Drug Development initiatives. By embedding scientifically sound and operationally feasible standards in this guideline, VPH believes EMA can position the EU as a global leader in the regulatory use of mechanistic models.
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