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

The Food and Drug Administration is seeking applications to develop physiologically based pharmacokinetic (PBPK) model-based mechanistic in vitro in vivo correlations (IVIVCs) for long acting injectable suspensions and implants. The goal of the project is to develop a bottom-up mechanistic PBPK model for these two types of long acting injectables by accounting for the influence of critical formulation attributes. The model formulation parameters and relevant physiology should be informed with suitable in vitro and in vivo experiments. • The use of PBPK modelling provides a unique opportunity to understand how the physicochemical properties of drug molecules/polymer, implant specific properties, critical formulation attributes, and physiology influence the in vivo release mechanisms of long acting injectable drug products and their disposition characteristics. • The project aims to define the 'safe space' for critical formulation attributes relevant to the reference listed drug product, explain sources of PK variability, and extrapolate predictions to human subjects by leveraging animal model data and accounting for species-specific physiological differences. • The award will be in the form of a cooperative agreement. • Eligible applicants include independent school districts, public housing authorities, Native American tribal organizations, faith-based or community-based organizations, and non-domestic entities.