Certara awarded $400,000 by FDA

ST. LOUIS—A grant from the U.S. Food and Drug Administration (FDA) will support the enhancement of a technology that is playing an increasingly important role in the drug development process. The Office of Generic Drugs has awarded Certara a three-year grant valued at up to $400,000 to support expanded capabilities for its Simcyp Simulator, a physiologically based pharmacokinetic (PBPK) modeling platform. The platform, which is used by most major pharmaceutical companies and regulatory agencies, is used to analyze dosing regimens, determine drug-drug interactions, inform study design and guide appropriate labeling language.

The grant will fund Certara’s efforts to enhance the Simcyp Simulator’s dermal absorption model, called MechDermA. The improved platform will provide a greater ability to assess the bioequivalence of drugs absorbed through the skin and to account for variability among individuals.

In recent years, PBPK models have been used with increasing frequency in the review process at the FDA’s Office of Clinical Pharmacology, with at least 136 drug submissions in the last seven years having relied on such modeling. Certara’s grant reflects the potential for PBPK models to also play an important role in the review of new generic drugs.

Amin Rostami, vice president of research and development at Certara, tells DDNews that these new capabilities will prove especially valuable for companies attempting to receive regulatory approval for new generic drugs that are absorbed through the skin. Due to the challenges involved in assessing the bioequivalence of such drugs, it can be particularly difficult and costly for generic drug companies to achieve regulatory approval. The enhanced MechDermA is expected to streamline and improve this process of determining bioequivalence by providing the ability to conduct a virtual assessment.

Most new capabilities and features developed for the Simcyp Simulator are designed to serve the needs of major pharmaceutical companies and other current users of the platform. Many of these current clients are members of the Simcyp Consortium, a group that guides scientific development of the platform so that it meets the needs of its current users. The newly released version 14 of the simulator, for instance, includes a range of new capabilities that were identified as important by members of the consortium, such as enhanced oral absorption modeling and improved gut wall modeling. The FDA grant, however, provided Certara an opportunity to develop new capabilities for the simulator beyond what the consortium has identified as priorities.

“These enhancements allow us to take our platform beyond its current use into the generic area,” says Rostami. “This is one of the ways that Simcyp is being recognized by regulatory agencies and researchers as a valuable tool with great potential for a diverse range of uses.”

Although the enhanced MechDermA may be especially useful for generic drug companies, Rostami says it could also serve important purposes for pharmaceutical companies with proprietary drugs under current patents.

“If they change the location where they produce a drug or change the materials involved, they are required to show the bioequivalence of the new product,” he explains. “The new capabilities we will develop with this grant could streamline that process.” Rostami also sees the potential for the platform to serve purposes beyond modeling drugs, such as providing cosmetics or chemicals companies new ways of assessing how their products are absorbed through the skin.

One potential advantage of PBPK models such as the Simcyp system is their ability to account for variability in human physiology when predicting drug absorption, distribution and elimination. The Simcyp platform was originally created to simulate clinical trials by accounting for the variability between individuals in its simulations instead of simply basing its modeling on an supposedly average person. The FDA grant will enable Certara to further develop the capability of the platform to incorporate such variability.

“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 pediatric 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 Jagiellonian University in Krakow, Poland.

The new model is also expected to 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.