Certara, the leading global technology-enabled drug development and drug safety consultancy, has received a Food and Drug Administration (FDA) Office of Generic Drugs grant (#1 U01 FD005225-01) to further develop and validate its Simcyp Simulator’s mechanistic dermal absorption model, MechDermA. Certara will enhance its physiologically-based pharmacokinetic (PBPK) modelling and simulation platform to assess the bioequivalence of drugs absorbed through the skin, while also factoring in variability in specific populations.

The current model’s capabilities first attracted the scientific community’s attention when they were outlined in a Journal of Pharmaceutical Science paper published in July 2012 that received “Editor’s Pick” status. That abstract is available here.

“We are delighted to receive this FDA grant, which further validates our stance that PBPK modeling is an indispensable tool in a cost-effective and efficient drug development programme,” said Certara chief executive officer, Edmundo Muniz, M.D., Ph.D.

Certara will use this FDA grant to further develop its Simcyp Population-Based ADME Simulator, which currently offers flexible and scientifically-validated algorithms for several PBPK models, including dermal absorption. This platform was originally created to simulate clinical trials and already factors variability between individuals into its simulations instead of just modelling an “average person.” It is already being used by most of the big pharmaceutical companies, regulatory agencies, academic, and not-for-profit organisations around the world.

“Our current dermal model on the Simcyp Population-Based ADME Simulator is based on the skin physiology of healthy male and female Caucasian subjects. This FDA grant will enable us to enhance that model to include paediatric and geriatric populations, additional ethnic groups, and specific diseases,” said Dr. Sebastian Polak, principal scientist in Certara’s Simcyp Business Unit and associate professor at the Jagiellonian University in Cracow, Poland.

“Our new model will also take into account other mechanisms that play an important role in dermal absorption, such as skin surface pH, dermal hydration, skin appendages, binding to keratin, and the effect of permeability-modifying formulation ingredients and drug-physiology interactions,” added Certara senior research scientist Nikunj Patel, who is co-lead on this project.

PBPK models offer a unique advantage over other approaches; they not only factor in the drug and its formulation characteristics but also the underlying human physiology and its variability when predicting drug absorption, distribution and elimination. As a result, these models are better predictors of population kinetics, including variability between individuals, making them a powerful assessment tool from a product development and regulatory perspective.

This three-year grant has a potential value of nearly $400,000, providing that specific conditions are met.

Views expressed here do not necessarily reflect the official policies of the FDA, nor does any mention of trade names, commercial practices, or organisation imply endorsement by the United States Government.