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.

Public Health Relevance

The goal of this project is to develop and validate general physiologically based pharmacokinetic (PBPK) software for long-acting injectable (LAI) microspheres including both microsphere and active pharmaceutical ingredient (API) to relate critical quality attributes to in vitro and in vivo performance and to evaluate bioequivalence criteria for LAI microspheres. This will be done by building on the existing GastroPlus? PBPK in vivo software platform and on the existing DDDPlus? in vitro dissolution/release simulation platform.

National Institute of Health (NIH)
Food and Drug Administration (FDA)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZFD1-SRC (99))
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Simulations Plus, Inc.
United States
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