Simcyp™ PBPK Simulator

In the last decade, PBPK modeling and simulation has soared in its use and applicability—Simcyp, working with its industry, academic and regulatory partners has led the way. The Simcyp Simulator is employed across the drug development cycle:

• For early pharmacokinetic determination of first-in-human dosing and to answer other translational questions;
• Leveraged to support strategic decision-making, the Simulator provides valuable information for designing clinical trials, to reduce trial size and complexity and to obtain clinical trial waivers;
• The Simulator quantitatively evaluates and predicts drug-drug interactions (DDIs) involving drug-metabolizing enzymes and membrane transporters, to evaluate PK variability as a function of ethnicity, organ impairment, and pharmacogenomics;
• It predicts dosing recommendations for different populations of patients, including pediatrics, geriatrics, ethnicities, organ impairment.

Adopted by 11 global regulatory agencies including the US FDA, Japan’s PMDA, UK’s MHRA and others, the Simcyp Simulator has been used to inform scores of drugs, replacing the need for clinical trials and providing prescribing information for approximately 300 label claims.

Beyond the work within the Consortium, the Simcyp team has collaborated with other organizations and funded its own research to develop unique modules.  While connected to the Simulator, they require additional and optional licensing.

Specialized modules are:

• Simcyp Pediatric
  Simcyp® Pediatric Simulator is the industry’s most sophisticated technology for modeling drug performance and determining dosing in neonates, infants, and children.  The Simulator contains extensive libraries on demographics, developmental physiology, and the ontogeny of drug elimination pathways.
• Simcyp Cardiac Safety Simulator (CSS)
  CSS is a systems biology-driven modeling and simulation-based platform for the assessment of the pro-arrhythmic potency of drugs, new chemical entities, and other xenobiotics within the targeted clinical population.  It enables early assessment of cardiac liability and is used for both pre-clinical and clinical assessment of cardiac risk.

• Simcyp Long Acting Injectable (LAI)
  LAI drug delivery provides advantages for specific drugs and patient types, including reduced toxicity, reduced dosing frequency and enhanced compliance. Simcyp’s LAI module is used to design experiments, narrow down promising formulation candidates, determine animal studies or clinical trials and fine-tune formulation based on study details.

• Simcyp Lactation
  Unfortunately, dosing information for pregnant and lactating women is generally not available on the drug label. Simcyp has been focused on this topic, looking at women’s health across the gestational cycle.  Simcyp lactation module predicts drug exposure in the mother and the milk to be given to the child, allowing for proper dosing of this fragile population.
• Simcyp Designer
  Simcyp Designer is a user friendly environment to quickly develop pharmacodynamic and/or quantitative systems pharmacology models and link them the Simcyp PBPK model and modify or expand those models.
• Virtual Bioequivalence
  The Virtual Bioequivalence (VBE) module facilitates running a range of common BE studies incorporating within and between subjects variability and batch to batch formulation changes. It also allows conducting BE statistical analysis, assess power of virtual BE studies and determine clinically relevant dissolution safe space.