FDA exploring model master files to expedite generic drug development
The US Food and Drug Administration (FDA) is exploring the use of model master files (MMFs) to enable sponsors to use the same modeling approach to support different generic drug development programs, potentially from different sponsors, in lieu of conducting clinical studies, according to officials who spoke at a 3 May workshop.FDA officials also provided an update on different modeling approaches used in new drug applications and generic drug applications at the workshop, which was sponsored by FDA and the Center for Research on Complex Generics (CRCG).
In its announcement of the workshop FDA stated that the MMF “is a framework aimed at model-sharing and model-reusability. Like drug master files, MMFs can be referenced by multiple applications for a similar purpose of use, thus improving model sharing, model standardization, and regulatory consistency and efficiency.”
The idea for a MMF was proposed at a 2022 FDA/CRCG virtual public workshop on best practices for using modeling approaches to support generic product development.
A MMF can use any type of model informed drug development (MIDD) approach, including real world data (RWD) and real-world evidence (RWE), fit-for-purpose, and physiologically-based pharmacokinetic models (PBPK) models. According to FDA, this shared modeling tool can be used to develop solid oral dosage forms, long-acting injectables, and others.
At the workshop, Shiew-Mei Huang, deputy director of the Office of Clinical Pharmacology (OCP) at FDA’s Center for Drug Evaluation and Research (CDER) pointed out that some of the advantages of the MMF is that it can simplify drug development if different sponsors are using the same model for drug development and this can eliminate duplicative reviews.
The drawback is that sponsors may be unwilling to share an MMF; in addition, the model may not work for highly-variable drugs.
Hao Zhu, division director for the division of pharmacometrics within OCP, noted parallels to FDA’s Fit-for-Purpose Initiative. The agency has so far signed off on the use of four models as drug development tools by drugmakers, such as Janssen, Novartis, and Pfizer, and other researchers. Three of these tools pertain to dose-finding studies for various diseases, while one is a simulation tool for planning Alzheimer’s disease trials.
Yuching Yang, team lead for the division of pharmacometrics in CDER, said she has no knowledge of the MMFs being used in the PBPK space, yet indicated that the number of NDA and BLAs submission containing PBPK analyses continues to grow: the number of applications containing these elements grew from five in 2011 to 33 in 2023. She added that this model is primarily used for drug-drug interaction studies.
A PBPK analysis uses models and simulations combining physiology, population, and drug substance and product characteristics to describe the pharmacokinetic or pharmacodynamic behaviors of a particular drug product; the idea behind using this technique is that it helps predict systemic drug exposure from oral drug products.
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