New grants support FDA’s GDUFA priorities of expanding bioequivalence methods for topical dermatological products and improving PBPK models of drug absorption via complex delivery routes
Certara, the global leader in model-informed drug development, regulatory science, real-world evidence and market access, has been awarded two new dermal virtual bioequivalence grants by the US Food and Drug Administration (FDA).
Bioequivalence studies are vitally important to ensure that the absorption rate and extent of test drug products are not significantly different to that of the comparable reference drug products. They are also used to verify that changes in manufacturing site, raw material suppliers or minor adjustments to a drug’s formulation do not substantially change its in vivo performance.
“We are delighted to receive additional US FDA support for the continuing development of our dermal physiologically based pharmacokinetic (PBPK) modelling and simulation program to conduct virtual bioequivalence studies. Virtual bioequivalence represents an ideal application for Simcyp’s PBPK modelling and simulation capabilities."
"In addition to providing additional insight into drug performance, these in silico studies are safer, faster and less expensive to conduct than clinical bioequivalence studies. As a result, these new grants represent an important advance for generic and innovator drug companies alike. We look forward to partnering with the US FDA to advance this field,” said Certara’s Simcyp President and Managing Director, Steve Toon, PhD.
Certara’s Simcyp Division will lead the project, entitled “Characterize Skin Physiology Parameters Utilized in Dermal PBPK Model Development Across Different Skin Disease States.”
This grant will fund enhancements to Certara’s PBPK multiphase, multilayer (MPML) MechDermA skin model to include the quantitative description of disease-triggered histological and functional modifications to the skin.
The resulting models will be able to factor in the thickness of various skin layers, presence of cracks, dryness, modification of blood flow and skin temperature, sebaceous gland infection and inflammation, flaking and the presence of pustules, comedones, vacuoles, cysts, and pseudocysts.
Histopathological modifications to Simcyp’s healthy skin model will permit development of models for specific skin diseases. The resulting disease models will all be verified using clinical data from the literature.
The inclusion of skin disease states in PBPK models will help pharma companies to develop non-Q1/Q2/Q3 formulations and simulate their in vivo performance in patient populations to further support their substitutability in diseased skin.
In evaluating bioequivalence, the FDA uses Q1 to define qualitative equivalence (test and reference products contain the same active and inactive ingredients), Q2 for quantitative equivalence (test and reference products contain the same amounts of active and inactive ingredients) and Q3 for physicochemical attributes of a specific dosage form.