certara-logoCertara, the leading provider of decision support technology and consulting services for optimising drug development and improving health outcomes, has released version 16 of its Simcyp Population-based Simulator.

The Simcyp Simulator is the pharmaceutical industry’s most sophisticated platform for determining first-in-human dose selection, designing more efficient and effective clinical studies, evaluating new drug formulations, and predicting drug-drug interactions (DDIs) and pharmacokinetic (PK) outcomes in clinical populations. These include vulnerable populations such as paediatric patients, pregnant women and patients with impaired organ function.

The Simcyp Simulator is also frequently used to inform drug label language and has regulatory acceptance from the US Food and Drug Administration (FDA), the European Medicines Agency and the Japanese Pharmaceuticals and Medical Devices Agency. For example, the Simcyp Simulator has been leveraged to inform more than 100 label claims for new drug approvals from FDA in the past few years. These label additions include potential DDIs, dosing regimens and data about new populations.

“The Simcyp Simulator is playing such a pivotal role at all stages of the drug development and regulatory process that our annual system update has become a major event,” said Simcyp President Steve Toon, PhD. “We are proud to introduce significant enhancements to our lung, skin and gastrointestinal (GI) tract models this year as well as time-saving administrative tools such as the Simcyp Report Assistant.”

Most of the top-40 pharma companies (including all of the top 10) are members of the Simcyp Consortium, which requested these new product developments.

Simcyp’s whole body simulation methodology can predict the PK and pharmacodynamics (PD) 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 with different demographics and ethnicities.

The Simcyp Simulator v16 offers several new features, including the following

  • Enhanced lung model: A mechanistic, multi-compartment granuloma model, consisting of macrophage, interstitial fluid, caseum and blood, has been added to the permeability limited lung model. Development of this PK/PD model, which can predict how drugs will be dispersed in the lungs at different stages of tuberculosis (TB) infection, was partly supported by the Critical Path to TB Drug Regimens initiative. This model permits four drugs, with different dosing regimen, to be studied concurrently. This is especially important as the most common dosing regimen for TB uses four drugs.

 According to the World Health Organization (WHO), TB is one of the top 10 causes of death worldwide and is the leading killer of HIV-positive people. In 2015, 10.4 million people fell ill with TB. Ending the TB epidemic by 2030 is among the health targets of the newly-adopted WHO Sustainable Development Goals.

  • New dermal absorption model: This new multiphase, multilayer skin model, which is supported by an FDA GDUFAR grant, will enable the virtual bioequivalence assessment of two drug formulations such as cream versus gel or the same formulation type with a different pH, viscosity or base. The model takes into account a range of mechanisms that play an important role in dermal absorption, such as skin surface pH, dermal hydration, skin appendages, binding to keratin, and drug-physiology interactions. Additionally, the model is further being developed to identify drug dermal absorption responses in a range of new populations, including pediatric and geriatric, additional ethnic groups, and specific diseases.
  • Enhanced GI transit model: The Simcyp Simulator’s ADAM (Advanced Dissolution Absorption Metabolism) model can now simulate a drug’s transit through the GI tract even more accurately using the new Segregated Transit Model. Certara has collected and analysed the available data in the literature on transit times in the GI tract and small intestine and entered it into the simulator. PBPK enables improved understanding and decision making around the issue of drug absorption, supporting drug development, formulation optimisation and regulatory approval.
  • Enhanced paediatric model: Users can now enter their own model for renal function and include the liver transporter’s ontogeny in this model. The paediatric biologics module also allows user-defined IgG catabolic and systemic clearance ontogeny profiles for large molecules. Simcyp’s paediatric module allows PK behaviour to be modeled in neonates, infants and children. PBPK is now considered to be a key component of paediatric drug development, especially for infants and neonates.
  • New Report Assistant: The new Simcyp Report Assistant streamlines reporting of PBPK analyses for regulatory submission or internal use. It compiles the appropriate PK/PD data and generates the necessary reports in Word automatically.

In addition, the Simcyp Simulator parameter estimation and sensitivity analysis capabilities are extensively expanded and it now provides biologics models and a biologics database for its Monkey Simulator.