Presenter
Eleftheria Tsakalozou, PhD
Lead Pharmacologist
Division of Quantitative Methods and Modeling (DQMM)
Office of Research and Standards (ORS)
Office of Generic Drugs (OGD)
Center for Drug Evaluation and Research (CDER)
US Food and Drug Administration (FDA)
Abstract
Eleftheria Tsakalozou presents on developing and submitting a Model Master File (MMF) during the 2025 Model Master Files Webinar. She defines MMFs as information and data on an in silico quantitative model or modeling platform supported by sufficient verification and validation. MMFs are designed to support model integrated evidence (MIE) approaches, encompassing a range of quantitative methods and advanced data analytics like machine learning and artificial intelligence. The presentation outlines different types of MMFs, such as those specific to a drug product, an in silico framework for a route of administration, or a modeling methodology for a context like bioequivalence assessments. The core content of an MMF submission includes the regulatory context of use, scientific rationale, comprehensive data analysis (with model analysis report and files), and an orientation file. Tsakalozou highlights the benefits of MMFs, including enhanced efficiency, consistency, communication, reduced time and costs for industry, and ensuring confidentiality of proprietary information. Using mock examples, she demonstrates the reusability and shareability of MMFs across multiple products or applicants. Finally, the presentation details the submission process, explaining that MMFs are submitted to the FDA as Type 5 Drug Master Files, which are reviewed in conjunction with pre-market applications, supporting regulatory submissions through validated modeling and simulation.