Developing PBPK Model-Based Mechanistic IVIVCs for Long Acting Injectable Suspensions and Implants (U01) Clinical Trial Optional

The contract aims to advance the development of physiologically based pharmacokinetic PBPK model-based mechanistic in vitro in vivo correlations for two prominent types of long acting injectables crystalline suspensions and polymer based implants by integrating their distinct formulation characteristics into a unified predictive framework. The project seeks to build a bottom up mechanistic PBPK model that accurately captures how drug molecule and polymer physicochemical properties implant design and critical formulation attributes influence in vivo release patterns and systemic disposition. This requires close alignment between in vitro experiments and in vivo data to inform model parameters and ensure biological relevance with validation supported by appropriate preclinical animal models that reflect human physiological differences. Once established the PBPK model will serve as a tool to define the safe space for key formulation variables tied to the reference listed drug enabling better understanding of pharmacokinetic variability and improving predictability across human populations by leveraging animal derived data adjusted for species specific physiology. The approach emphasizes mechanistic insight over empirical fitting allowing for robust extrapolation and regulatory decision making. The initiative is funded by the Food and Drug Administration under the Department of Health and Human Services with Terrin Brown serving as the primary point of contact for grants management and can be accessed through the official grants portal.