The Better Way - Virtual Bioequivalence

Demonstrating bioequivalence (BE) remains the key regulatory hurdle for generic drug approval.  The high cost of running clinical BE trials is also a challenge.

As a result, some branded drugs remain on the market past the originator’s patent expiration, without cost-effective generic alternatives that could benefit patients.

In silico modeling & simulation, specifically physiologically-based pharmacokinetics (PBPK) leveraging in vitro data, could be a cost-effective option in lieu of running an in vivo comparative clinical BE endpoint study.

Simcyp™ MechDermA Model

Our mechanistic MPML-MechDermA model of the skin absorption accounts for the active pharmaceutical ingredient (API), formulation, physiology, and environmental parameters, enabling the simulation of complex diffusion through the SC for drugs with different physicochemical properties as well as different formulations, namely gels, emulsions, patches, suspensions, and pastes.

The model can also simulate drug partitioning and absorption through the hair follicular pathway with blood flow to the dermis modeled as a function of cardiac output, body weight, and body surface area.

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First FDA approval of complex generic with virtual bioequivalence (VBE)

The FDA’s approval of a generic version of diclofenac sodium topical gel leveraging the Simcyp MechDermA PPBK model sets the stage for increased use of M&S to speed the approval of complex generics.

Certara’s VBE uses advanced modeling and simulation to demonstrate BE and provide additional insight into drug performance.

These in silico studies are safer (removing the need for drug administration to often young, healthy volunteers), faster and less expensive to conduct than clinical BE studies.

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Advancing new drug development with MechDermA Model

The use of the Simcyp Simulator allowed Galderma to expedite and inform its drug development program, while providing safety label claim and pediatric dosing information without the need for testing in clinical patients.

“We were pleased to partner with Certara to develop this detailed physiologically-based pharmacokinetic (PBPK) model of trifarotene, which helped to demonstrate the safety of our new drug and also provide additional prescribing information for our new drug label,” said Nathalie Wagner, Senior Clinical PK Manager at Galderma. “As a leader in modern research and development of scientifically-defined and medically-proven solutions for the skin, we embrace new technologies such as modeling and simulation that improve our effectiveness.”

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Sebastian Polak, PhD Senior Scientific Advisor & Head of Mechanistic Dermal Modelling

Bastek leads the development of dermal models at Simcyp and cardiac safety modeling and simulation system – Cardiac Safety Simulator. He is also a tenured Professor in Biopharmaceutics at the Faculty of Pharmacy at Jagiellonian University in Krakow, Poland.

Nikunjkumar Patel, PhD Senior Consultant and Biopharmaceutics Scientific Advisor

Nikunj has more than 11 years of experience in computer aided drug design and PKPD modelling including 8+ years of experience focusing on PBPK modelling. He joined Certara’s Simcyp division in 2011 and worked extensively on oral and dermal absorption PBPK Modelling and mechanistic cardiac safety risk assessment. He has a doctorate degree in Quantitative Systems Toxicology and Safety.