Dermal Formulation Quality by Design Project Abstract
The Office of Generic Drugs (OGD) is tasked, among other things, with reviewing sponsor applications for
dermal dosage forms that purport to be bioequivalent to the 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) and mechanistic absorption model (MAM) and accounts for formulation effects in
predicting the local drug concentration in the skin as well as concentration in systemic circulation can be a
useful tool to reduce the time and expense involved in designing new generic formulations and assessing
their potential to be bioequivalent to approved dosage forms by industry and regulatory scientists.
Developing a state-of-the-art capability for dermal MAM/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 advance the state-of-the-art for dermal MAM/PBPK modeling to include the
ability to identify and quantify drug-product-specific critical quality and performance attributes of
transdermal dosage forms. This will be achieved through a combination of expanding the existing
knowledge base and compiling a database of critical product quality and performance attributes for
transdermal formulations, as well as enhancing the models in the Transdermal Compartmental Absorption
and Transit™ (TCAT™) MAM/PBPK model within the GastroPlus™ software program to account for these
formulation attributes in the assessment of virtual bioequivalence between brand and generic drug
products. By basing the final software program on the well-established and validated TCAT model, which
is in use at the FDA and within the pharmaceutical innovator and generic industries 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).
Throughout the effort, we will maintain close contact with the FDA program manager and the Consortium
for Dermal Absorption Modeling (CDAM) that we will form with our collaboration partners and the FDA
to ensure the project team focuses on model development and new experimental work. This will result in
developing the optimum software capabilities to implement dermal product Quality by Design (QbD) and
virtual bioequivalence assessment, within the scope of the project.