Development of PBPK simulation for long-acting injectable microspheres - LAI Microspheres Abstract
The Office of Generic Drugs (OGD) is tasked, among other things, with reviewing sponsor applications for
long-acting injectable microsphere-based dosage forms that purport to be bioequivalent to approved
formulations for the same drug. Sponsor companies want to have high confidence that applications they
submit for dosage forms thought to be bioequivalent will receive favorable reviews. Software that embodies
physiologically based pharmacokinetics (PBPK) can be a useful tool to reduce the time and expense
involved in determining the likelihood that a new formulation will be bioequivalent to an approved dosage
form for both industry scientists and regulators.
Developing a state-of-the-art capability for LAI microsphere PBPK software requires an extensive
knowledge base to serve as the scientific foundation, talented scientists to apply the knowledge base in the
development of useful equations and logic suitable for software, high-level computer programming skills to
encode the equations and logic into user-friendly software, and experienced scientists to test, validate,
document, and support the software for use by others not involved in its development.
This proposed project will develop PBPK software for LAI microspheres through a combination of
expanding the existing knowledge base, development and implementation of enhanced physiological
models for human and animal dosing tissues in the existing GastroPlus™ software program, and validation
and documentation of the resulting software for use by others. By basing the final software program on the
well-established and validated GastroPlus PBPK model, which is in wide use in the pharmaceutical
industry today, we will be able to focus project resources entirely on advancing the capabilities of the model
rather than having to develop new code for the core program and its many support capabilities (e.g.,
integration, plotting, Parameter Sensitivity Analysis, Population Simulations, and drug-drug interactions).
Throughout the effort, we will maintain close contact with the FDA program manager and the Consortium
for LAI Microspheres (CLAIM) that we propose to form with our collaboration partners and the FDA to
ensure the project team focuses on software developments and new experimental work that will result in
developing the optimum software capabilities for LAI microsphere dosage form development and
comparison, within the scope of the project.
