The Role of Model Master Files for Sharing, Acceptance, and Communication with FDA

Area of Science:

• Pharmacometrics and Computational Toxicology
• Drug Development and Regulatory Science
• Quantitative Pharmacology

Background:

• The increasing use of Model Integrated Evidence (MIE) in generic drug development necessitates standardized approaches for model sharing and regulatory acceptance.
• Model Master File (MMF) is proposed as a framework for sharable, validated quantitative models suitable for regulatory submissions.
• Industry and regulatory bodies, including the U.S. Food and Drug Administration (FDA), recognize the potential benefits of MMFs.

Purpose of the Study:

• To summarize discussions from a 2022 FDA and CRCG workshop on best practices for utilizing modeling in generic drug development.
• To initiate dialogue on the further utility and best practices for applying MMFs in drug development and regulatory processes.
• To highlight the acknowledged advantages of MMFs and the need for stakeholder collaboration.

Main Methods:

• A virtual public workshop was convened by the FDA and the Center for Research on Complex Generics (CRCG) in 2022.
• Presentations and panel discussions focused on model sharing, acceptance, and communication with the FDA.
• This report synthesizes the key takeaways and outcomes from the workshop.

Main Results:

• Stakeholders, including model developers, industry, and the FDA, acknowledged the potential advantages of MMFs.
• The workshop served as a foundational discussion for establishing best practices in MMF utilization.
• There is a clear need for continued dialogue and cooperation to foster a unified understanding of MMFs.

Conclusions:

• MMFs offer a promising framework for regulatory acceptance of quantitative models in MIE.
• Further collaboration among stakeholders is imperative to establish standardized best practices for MMF application.
• A follow-up workshop is planned for May 2-3, 2024, to address practical aspects of MMFs in regulatory submissions.