Considerations for Regulatory Reusability of Dynamic Tools in the New Drug Development

Area of Science:

• Pharmacokinetics and Pharmacodynamics
• Computational Biology and Bioinformatics
• Regulatory Science

Background:

• Model-informed drug development (MIDD) is crucial for efficient drug discovery and regulatory submissions.
• Dynamic modeling tools, including population pharmacokinetics (popPK), physiologically-based pharmacokinetics (PBPK), and quantitative systems pharmacology (QSP), are increasingly vital.
• The Fit-for-Purpose (FFP) initiative and Model Master File (MMF) framework are emerging to support model reusability and sharing.

Purpose of the Study:

• To discuss considerations for the regulatory acceptance of dynamic modeling tools in new drug development.
• To share insights from a U.S. Food and Drug Administration (FDA) and Center for Research on Complex Generics (CRCG) workshop on dynamic tools and the MMF.
• To explore pathways for the regulatory acceptance of dynamic tools within the new drug space.

Main Methods:

• Review of presentations and discussions from a workshop focused on dynamic modeling tools and the MMF.
• Exploration of current practices in PBPK model evaluation and the application of popPK models in bioequivalence (BE) assessments.
• Discussion of challenges and opportunities related to model reuse, validation, and regulatory frameworks.

Main Results:

• Emphasis on the need for context-specific validation, version control, and adaptation to scientific advancements for model reuse.
• Highlighting the importance of clear regulatory pathways and structured frameworks for consistent application of reusable models.
• Recognition of the MMF's potential to streamline regulatory reviews and reduce redundancy, pending further operational detail.

Conclusions:

• Continued collaboration among stakeholders is essential for refining model-sharing practices and enhancing validation processes.
• Transparency and robust validation are key to ensuring MIDD approaches remain adaptable and effective for evolving regulatory needs.
• The MMF framework offers a promising avenue for improving the efficiency and consistency of dynamic tool utilization in drug development.