Certara, a global provider in model-informed drug development and regulatory science, has launched version 17 of its Simcyp Population-based Simulator.

“We are proud to introduce several significant advances in Simcyp Simulator v17, including new in silico cancer patient and premature baby populations, enhanced skin and gut transporter models, and additional compound qualification summaries. These enhancements will further improve drug development decision making and expedite regulatory submissions,” said Stephen Toon, BPharm, PhD, President and Managing Director of Certara’s Simcyp division. “It is a testament to our strong partnership with the Simcyp Consortium – 36 leading biopharmaceutical member companies, and numerous global regulatory agency and academic center affiliates – that we continue to make these major strides forward.”

Certara’s Simcyp Simulator is the 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 pediatric patients, pregnant women, and patients with impaired organ function.

The Simcyp Simulator links in vitro data to in vivo absorption, distribution, metabolism, and excretion (ADME) data and pharmacokinetic/pharmacodynamic (PK/PD) outcomes, allowing potential clinical issues to be explored prior to human studies. It provides crucial support for drug development decisions and is frequently used to inform drug labels.

Certara’s Simcyp Simulator v17 advances include the following:

Added an Oncology Population

The Simulator now includes a virtual oncology population that can be employed to model physiologically-based PK (PBPK) in cancer patients. This is an important addition to the Simulator because cancer patients are physiologically different from healthy volunteers. For example, cancer patients have different levels of blood and plasma binding proteins and hepatic transporters. As a result, a compound that could cause a DDI in a healthy population, might not in an oncology population and vice versa.

Added a Pediatric Population

Certara scientists have also added a premature child population, ranging in age from 28 postmenstrual weeks until one month after birth, to the Simcyp Simulator. It joins existing pediatric and pregnancy modules. In addition, they have included transporter ontogeny in the pediatric population. This is particularly important because transporter abundance and expression can change significantly in early life.

Enhanced the MechDermA Dermal Model

This multi-phase, multi-layer mechanistic dermal (MPML MechDermA) Simcyp Simulator model, which mimics a drug’s diffusion from the epidermis into deep tissue, is significantly expanded. The MPML MechDermA model was enhanced to include pediatric and geriatric populations, additional ethnic groups, and specific skin diseases such as psoriasis. The pediatric population is an important addition because as children grow, the thickness, hydration, and composition of their skin change.

Funded by a multi-year FDA grant, the MechDermA model allows researchers to estimate local and systemic exposure stemming from the topical or transdermal absorption of a medication or commercial chemical. It will be an asset for pharmaceutical or cosmetic companies developing patches, gels, creams or ointments and needing to conduct toxicology testing. The MechDermA model can also identify clinically-relevant product quality attributes, aiding in product specification.

Expanded the Gut Transporters and IVIVE Techniques in the ADAM/M-ADAM Models

Drug transporters can play a pivotal role in determining drug concentrations in the blood, liver, brain, intestine, lung, and kidney. As a result, transporter-mediated DDIs can affect the drug effectiveness and toxicity.

Certara scientists have included 14 more gut transporters in the Simcyp Simulator Advanced Dissolution, Absorption and Metabolism (ADAM) and Multi-layer ADAM (M-ADAM) models. They have also collated and analyzed transporter abundance values from the literature and incorporated them into both models.

Expanded the Qualified Compound Library

Certara has also expanded its compound database and significantly increased the number of compound qualification summaries (now more than 80) available in its library. These summaries provide background to the compounds’ parameters and demonstrate the Simcyp Simulator’s capability in mimicking clinical studies and support clients in their regulatory interactions with health authorities.

Enhanced the Animal Models

Certara has also added PD modeling capability to its Simcyp Rat, Mouse, Dog and Monkey Simulators, helping with preclinical species translation and supporting the industry in optimizing and reducing animal testing.

Incorporation of Enzyme Inter-correlations in Virtual Populations

Recent literature data have demonstrated significant inter-correlation in expression of liver enzymes. Accounting for such relationships is essential when generating virtual populations. The methodology, framework, and database have been provided to allow incorporation of the inter-correlations in absolute abundance values for 13 CYP450 hepatic enzymes.