Using $2.2 million in federal stimulus funds, Arizona is establishing a Biosignatures Laboratory tasked with developing standards for the consistent, reproducible measurement of biomarkers used in drug development.
Led by the Tucson-based Critical Path Institute and Roche's Ventana Medical Systems, the project aims to fill a gap in the current biomarker pipeline by standardizing assays used in their measurement, and will hopefully speed the progression of proposed biomarkers through the US Food and Drug Administration's qualification pipeline, C-Path CEO Raymond Woosley told ProteoMonitor.
C-Path and Ventana are currently negotiating a cooperative research and development agreement with the FDA, under which they will be developing biological standards that could be useful in cancer drug development.
Independently of this CRADA, the laboratory's biomarker assay standardization efforts will be "helpful, not only for the development of biological standards, but also as a resource for the analytical validation of tests used in biomarker qualification," Federico Goodsaid, associate director for operations in genomics at FDA, told ProteoMonitor.
"In the biomarker qualification requests that we've gotten so far, I would say that [assay standardization] is not a problem that can't be addressed, but it's a problem that requires quite a bit of work," he said. "Any way you have to make that … happen very early on in the qualification process obviously is very helpful."
Goodsaid cited as an example the submission of protein biomarkers for nephrotoxicity submitted in 2007 by C-Path's Predictive Safety Testing Consortium, a public-private partnership including sixteen global pharmaceutical companies (PM 05/14/10).
That submission "was a case where the [biomarker] tests were being developed as the platform to run the tests was being developed," he said. "Needless to say, you didn't have 10 different labs running the same platform. So obviously under those conditions it becomes difficult to do an exhaustive analytical validation of the test."
In that example, the nephrotoxicity markers "were all originally developed on ELISA. Then the ELISAs were transferred to multianalyte platforms, and there's always quite a bit of work needed to make that transfer," he said. "We've done quite a number of protein biomarkers, and we've seen some of the issues that come along when you try to establish the analytical performance of the test."
"Science is moving very quickly," Woosley said. "[Biomarker work] is published in medical journals, but then to put it into use in a medical environment or a clinical research environment is often very difficult. So we believe that some of these emerging biomarkers could benefit from a real good look at how you standardize them and implement them across multiple clinical trials."
Through the Biosignatures Laboratory, C-Path hopes to create what Woosley called "one-stop shopping for biomarker evolution." The organization, he said, aims to provide resources at three stages of the biomarker pipeline – the development of standards for data elements, which it does in collaboration with the Clinical Data Interchange Standards Consortium; the development of assay standards, which the new laboratory will provide; and the regulatory qualification process.
Biomarker development is currently being "done in pieces around the country," Woosley said. "For instance, for the [PSTC's nephrotoxicity] biomarkers, industry was willing itself to compare the different measure of those biomarkers to set the analytic standards. But the goal of the grant is to create a resource where people could get all three – they can get the standards, they can get the assay performance, and they can get the qualification if they want."
With regard to protein biomarkers, cerebrospinal fluid markers for Alzheimer's disease will be among the first the laboratory will investigate. Protein biomarkers including amyloid-beta1-42 and total tau have shown utility in diagnosing Alzheimer's disease and predicting progression to the disease in subjects with mild cognitive impairment, but researchers have had some difficulty reproducing CSF protein measurements across laboratories (PM 06/11/2010).
The laboratory will also likely work on assays for additional nephrotoxicity protein biomarkers that are currently being researched, Woosley said. In terms of the assay platforms the laboratory's work will concentrate on, he said that ELISA and mass spec would be primary areas of focus as well as microarrays, due to the fact that most assays will probably involve the measurement of multiple proteins.
In addition to C-Path, Ventana, and the FDA, the Biosignatures Laboratory will involve collaborations with researchers from institutions including the Biodesign Institute at Arizona State University, the Arizona Cancer Center, University of Arizona Health Sciences Center, the International Genomics Consortium, and the Translational Genomics Research Institute.
The project is being funded by Science Foundation Arizona – a non-profit public-private group that promotes development of the state's biotech and other tech industries – with money from the American Recovery and Reinvestment Act. As is required with SFAz grants, the project is also receiving a $2.2 million industry match from several unnamed pharmaceutical companies.
Moving forward, C-Path and its partners at Arizona State, the University of Arizona, and the International Genomics Consortium will be responsible for obtaining funds to keep the project going, Woosley said.
"Part of accepting these funds is a commitment to finding [additional] funds going forward," he said. "Hopefully the four of us as a group can sustain this effort."