Stuck in the MIDD-le
Why companies want flexibility in guidance on PK modeling tools
An FDA meeting to discuss evidentiary standards for model-informed drug development revealed concerns that rigid regulatory requirements could undermine the utility of the approach. Rather than specifying requirements for qualifying models as EMA has done, panelists suggested FDA should make clear what types of information it needs from sponsors to evaluate models based on the logic that goes into constructing them.
Differences in these approaches represent a trade-off between the amount of data and near-term investment required to qualify a model for repeated use, and the amount of effort required over the long term to validate a model for every application.
Model-informed drug development (MIDD) serves two main purposes: to streamline drug development by replacing some experimental data collection with simulated data, and to generate information that cannot or would not be obtained experimentally.
Companies and regulators have used MIDD to understand target concentrations and therapeutic windows, probe drug-drug interactions, select doses, optimize dosing in difficult-to-test populations such as children, and correlate trial endpoints with clinical outcomes. The approach has allowed some companies to run shorter or smaller trials, and conduct fewer postmarketing studies.
Integrating MIDD into more drug applications is one of FDA’s goals under PDUFA VI.
“If any one agency still requires clinical data to proceed, the benefit of PBPK modeling from the industry perspective will be greatly reduced.”
At the March