Most of the top 35 pharmaceutical companies are members of the Simcyp™ Consortium. The FDA, EMA, PMDA and other regulators use the Simcyp Simulator.
Predict Drug Performance from Virtual Populations
The Simcyp Simulator is the pharmaceutical industry’s most sophisticated physiologically based pharmacokinetics (PBPK) platform for determining first-in-human dosing, optimizing clinical study design, evaluating new drug formulations, setting the dose in untested populations, performing virtual bioequivalence analyses, and predicting drug-drug interactions (DDIs). Simcyp is being applied to small molecules, biologics, ADCs, generics, and new modality drugs.
- The Simulator includes extensive libraries on demographics, developmental physiology and the ontogeny of drug elimination pathways;
- An unmatched body of science, the Simulator includes 10 advanced mechanistic organs, 29 sub-populations, and 115+ compound files for use by member companies;
- Links in vitro data to in vivo absorption, distribution, metabolism, and excretion (ADME) and pharmacokinetic / pharmacodynamic (PK/PD) outcomes to explore clinical scenarios and support drug development decisions;
Simcyp PBPK models describe the behavior of drugs in relevant body tissues and organs. Each organ may be described by one or several physiological compartments. The concentration of the drug in each compartment is determined by combining systems data, drug data, and trial design information. The Simulator includes a unique set of genetic, physiological and epidemiological databases that facilitate simulating virtual populations with different demographics, ethnicities, and disease states.
New capabilities in Version 22 include:
- Expansion of compound library which expedites assessment of DDIs for a wider variety of therapeutic compounds
- Additional populations allows simulation of the increasingly diverse North American patient populations
- Enhancement of subcutaneous dosing capabilities improves bioavailability predictions after sub-cutaneous dosing
- Improved flexibility in simultaneous fitting facilitates integration of data from multiple sources
Version 22 also features updates to Simcyp modules for pediatric populations, pregnancy and lactation, dermal absorption, long acting injectibles (LAI), virtual bioequivalence and in vitro to in vivo extrapolation (IVIVE), mechanism-based inhibition (MBI) of metabolism, and oral absorption.
Analyze complex in vitro data using whole cell, tissue samples and solid dosage samples to assess the exposure, metabolism, transport, and dissolution/solubility of drugs
Simcyp™ Animal is a PBPK modeling platform for rat, dog, mouse and monkey, used to explain drug behavior that would be difficult to obtain via in vivo experimentation.
Delivering on the promise of PBPK
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.
Unique Capabilities—Specialized Modules
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.
Gaining the Simcyp Advantage through Consultancy
Innovative mid and smaller biopharmaceutical companies can gain the advantages of the Simcyp PBPK Simulator outside of joining the Simcyp Consortium or attaining licenses. Simcyp has a team of experienced and highly credentialed individuals that support smaller organizations on a per-project basis via consultancy. Generally, we begin with a feasibility assessment to determine if the appropriate data is available to conduct the modeling & simulation with a full project to follow.
Example projects include:
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Drug-drug interaction simulations – perpetrator and victim
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Absorption modelling – formulation effects/bioequivalence, food effect
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Dosing for special populations – pediatrics, elderly, organ impairment, disease conditions, ethnic differences
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Evaluation of drug performance from extrinsic factors – smoking, alcohol
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Novel routes of administration – dermal, inhalation, long-acting injectable, rectal, intravaginal
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Biologics – mAbs, ADCs, other proteins, cytokine mediated DDIs
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Virtual bioequivalence and formulations for complex generics
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Early PK prediction, FIH dosing
