Certara Supported Risk Assessment Research Wins Outstanding Paper Award

PRINCETON, NJ - Mar 27, 2015 - Certara®, the global biosimulation technology-enabled drug development and drug safety consulting company, today announced that the Toxicological Sciences article, entitled “Incorporating Population Variability and Susceptible Subpopulations into Dosimetry for High-throughput Toxicity Testing,” using its Simcyp® Simulator, has been selected by the Risk Assessment Specialty Section (RASS) of the Society of Toxicology (SOT) as its “Best Published Paper Advancing the Science of Risk Assessment.” This award was presented during the SOT 54th Annual Meeting and ToxExpo™, which was held from March 22-26 in San Diego, CA.

There are more than 84,000 chemical substances that are manufactured or processed in the U.S. included in the U.S. Environmental Protection Agency (EPA) Toxic Substances Control Act Inventory. That list does not include items such as pesticides, drugs, tobacco and nuclear material, which are subject to other U.S statutes. The EPA's Integrated Risk Information System, which evaluates information on health effects that may result from exposure to environmental contaminants, contains only 558 chemical substances. Therefore, there is a large unmet need for efficient toxicology testing strategies. But this is a complex field as chemical exposure effects can vary by age, gender, ethnicity, and a person’s liver/kidney function.

“There is a growing desire to use in vitro high-throughput screening (HTS) to evaluate the impact of certain chemicals on human health. It’s an efficient, economical, and humane alternative to animal tests,” said Certara Consultant and Scientific Advisor, Dr. Lisa Almond. “But to be able to produce an accurate risk assessment, we need to integrate dosimetry into the HTS assays and factor in population variability. This paper describes how the Hamner Institutes applied the Simcyp Simulator to help achieve these goals.”

This study measured the in vitro clearance rates for nine chemicals metabolized by 18 chemical-metabolizing enzymes (13 cytochrome P450 and five uridine 5'-diphospho-glucuronysyltransferase). The resulting clearance rates were then incorporated into an in vitro in vivo extrapolation computer model, which used Certara’s Simcyp Simulator to account for known differences in enzyme expression for several different age groups and ethnicities.

When median readings from a healthy population were compared with more sensitive populations, it revealed 1.3- to 4.3-fold or 3.1- to 13.1-fold differences compared to the median and 95th percentiles, respectively. This research could be used to determine chemical-specific human toxicokinetic adjustment factors for different populations. Thus, it could help ensure that adequate protection is provided for sensitive populations such as young children, the elderly, and people with liver and renal impairment.

This project was led by Dr. Barbara Wetmore of the Hamner Institutes for Health Sciences in partnership with colleagues at the EPA and Dr. Almond from Certara’s Simcyp consulting group.

About Certara
Certara is the global biosimulation technology-enabled drug development and drug safety consulting company. Its customers include hundreds of biopharmaceutical companies around the globe, together with several regulatory agencies. Certara’s solutions, which span the discovery, preclinical and clinical stages of drug development, enable data-driven decisions, leading to more precisely designed trials with a reduced risk of failure and improved subject safety. For more information, visit www.certara.com.