Certara, a global biosimulation technology-enabled drug development company, announced the release of version 15 of its Simcyp population-based simulator. The Simcyp simulator is the pharmaceutical industry’s most sophisticated physiologically-based pharmacokinetic (PBPK) modeling and simulation platform for determining first-in-human dose selection, predicting drug-drug interactions (DDIs), understanding drug disposition in special populations, including paediatrics, and bridging to virtual ethnic populations.

The Simcyp simulator has increasingly been used to inform drug label language, with regulatory acceptance from the US Food and Drug Administration, the European Medicines Agency, and the Japanese Pharmaceuticals and Medical Devices Agency.

“Our work provides a framework for assessing inter-individual variability in pharmacokinetics and pharmacodynamics using virtual human populations and integrating general knowledge of the physical chemistry of a drug with human biology, anatomy, physiology and genetics,” said Simcyp president Steve Toon, PhD.

“The Simcyp simulator allows us to accurately model drug disposition within human and various animal species so that we can inform on dose and dose regimen selection, DDIs, assess the impact of food effect on orally-administered medicines and evaluate impacts of disease and lifestyle factors.”

The Simcyp whole body simulation methodology can predict the pharmacokinetics and pharmacodynamics of small molecule and biological medicines using laboratory-derived data. The simulator includes a unique set of genetic, physiological and epidemiological databases that facilitate the simulation of virtual populations of differing demographies and ethnicities.

The majority of the top-40 pharma companies (including all of the top 10) are members of the Simcyp Consortium. The Simcyp simulator v15 contains several new models and features requested by the Simcyp Consortium, including:

Simcyp simulator v15 now offers a physiologically-based pharmacokinetic model for antibody drug conjugates (ADCs). ADCs are a new class of targeted therapies for oncology. They combine the ability of monoclonal antibodies to target cancer cells with the tumor cell killing ability of chemotherapy drugs. This new, scientifically complex therapeutic approach can have a breakthrough impact on the oncology market. According to the report “Global Antibody Drug Conjugate Market Outlook 2020,” the ADC market is anticipated to reach around $12.7 billion by 2020. This new Simcyp Simulator model enables mechanism-driven studies of ADCs and DDIs.

Certara has also enhanced Simcyp simulator’s ADAM (Advanced Dissolution Absorption Metabolism) model. ADAM now adjusts for factors such as particle shape. ADAM also now contains a new precipitation model that includes lag time. In addition, the multi-layer gut wall within ADAM (M-ADAM) can model drug concentrations within the unstirred boundary layer, enterocyte compartments, active and passive drug permeation, transporter DDIs at both the apical and basolateral membranes, and lymphatic absorption from the intestinal interstitial fluid to the systemic circulation. The enhanced ADAM model helps sponsors develop more physiologically accurate and flexible models of drug disposition in the gut. These improvements also facilitate understanding the role of transporters in influencing bi-directional drug distribution across the gut wall.

Certara is a trailblazer in modeling pediatric patient populations and biologics. The latest version of the Simcyp simulator facilitates modeling of biologics in pediatric populations. It incorporates age-related changes in system parameters such as IgG and IgE levels. Researchers can use this model to define population age, weight and height relationships. This new model provides unique insight into understanding the disposition of biologics in young children, an especially sensitive patient population.

Certara has also added a multiple-compartment permeability-limited lung model to the Simcyp simulator. It models active and passive drug disposition in the lungs. This model helps sponsors gain a better understanding of drug absorption and metabolism in the lung. This development is partly supported by the Critical Path to TB Drug Regimens initiative. The lung model complements the previously developed models of the brain, liver, and kidney.

The Simcyp simulator now comes bundled with a command line console which supports the Innovative Medicines Initiative’s DDMoRe Project Interoperability Framework. This new functionality will allow DDMoRe partners with a Simcyp simulator license to run simulations in scripted workflows with other software such as NONMEM and PSN, Monolix, PFIM, and PopED. The console may be used independently of DDMoRe facilities, and users will benefit from the Simulator’s vast databases of populations, compounds and PBPK models through other platforms such as Matlab and R.