Applied Biosystems and Asuragen collaborate with the Critical Path Institute to improve drug toxicity screening

Drug toxicity accounts for billions of lost dollars to the pharmaceutical industry each year and is a leading cause of pre-clinical drug failures. The US Food and Drug Administration (FDA) and other regulatory organisations have called upon the pharmaceutical industry to develop more effective tools to help avoid these costly failures, reduce the number of failed compounds, and bring better drugs to market sooner.

To help address this challenge, Applied Biosystems Inc. and Asuragen, Inc., a provider of pharmacogenomic services, are collaborating with the Critical Path Institute’s Predictive Safety Testing Consortium to develop a predictive gene signature panel that will allow pharmaceutical companies to screen potential therapeutics quickly and easily for toxic effects in pre-clinical samples.

As part of the collaboration, Critical Path Institute (C-Path), Applied Biosystems and Asuragen will partner to develop a panel of assays with gene targets determined to be associated with carcinogenicity in laboratory rats, a common model organism for pharmaceutical testing. The collaborators will also use the Applied Biosystems assays to determine and differentiate effects that are genotoxic from non-genotoxic modes of action to assist in risk assessment. The new biomarker panel will be based on Applied Biosystems’ TaqMan® Gene Signature Array and real-time PCR technology.

C-Path is a publicly funded, non-profit research and education institute. The institute was established in 2005 to create and support collaborations among industry, academic and governmental scientists that advance the FDA’s Critical Path Initiative, which is an endeavour to modernise the process for the development of medical products, including drugs, diagnostics and medical devices. The Critical Path Opportunities List, published by the FDA in March 2006, presents examples of how new scientific discoveries in genomics and proteomics, imaging and bioinformatics could be applied to improve the accuracy of the tests used to predict the safety and efficacy of investigational medical products.

“The development of robust turnkey assays to speed development of therapeutics for patients is one of the fundamental goals of the Critical Path Initiative, for which we believe we can make a difference working with partners such as Applied Biosystems and Asuragen,” said Dr William B Mattes, director of C-Path’s Predictive Safety Testing Consortium. “We expect this collaboration will facilitate broader utility of genomic biomarkers of toxicity across the industry in order to enable the early prediction and mechanistic understanding of potential carcinogens in pre-clinical research.”

The Predictive Safety Testing Consortium (PSTC) was established by C-Path to bring together major pharmaceutical companies to work in collaboration with C-Path and in coordination with the FDA. Its objective is to enable the exchange of knowledge and resources to speed drug development and improve drug safety. The Consortium currently has 16 members. Scientists from the FDA and its European counterpart, the European Medicines Agency, as well as academic experts also participate as advisors.

Increasingly, researchers are using Applied Biosystems’ comprehensive line of RNA analysis tools based on gold-standard TaqMan chemistry for the development of potential biomarkers. For this project, Applied Biosystems is providing PSTC scientists with its TaqMan Gene Signature Arrays. PSTC scientists will use this collection of RNA expression assays to develop a biomarker panel for use in screening potential therapeutics for carcinogenic effects in pre-clinical samples.

“Biomarkers that allow early prediction of toxicity will enable pharmaceutical companies to make better compound selection decisions and facilitate the early initiation of risk assessment work that would otherwise delay bringing important medicines to market,” said Peter Dansky, president of Applied Biosystems’ functional analysis division. “We are committed to continue expanding our menu of TaqMan Arrays for applications requiring a robust and highly sensitive detection system in an easy-to-use and standardised format, such as in high throughput drug screening.”

The development of tools that improve drug toxicity screening involves the generation and analysis of vast amounts of molecular data. Asuragen is contributing crucial laboratory services, pharmacogenomic expertise, and bioinformatics capabilities for the Predictive Safety Testing Consortium project.

“For this important project, Asuragen is committed to working with the Critical Path Institute and Applied Biosystems to help improve the drug development process,” said Dr Matt Winkler, CEO and CSO of Asuragen.