U.S. Agencies Working Collaboratively to Develop Novel Human Cell Platform for Drug Safety Testing

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U.S. Agencies Working Collaboratively to Develop Novel Human Cell Platform for Drug Safety Testing

Sherry Ward, AltTox Contributing Editor

Published: September 30, 2011

Force protection in the U.S. Department of Defense (DOD) involves much more than providing sophisticated advanced technology for the battlefield. Warfighters are also at risk of being exposed to existing or emerging diseases and bioterrorism agents. To respond to these potential threats, the DOD supports research into the development of safe and effective treatments and preventative measures such as drugs, antitoxins, and vaccines, which they call medical countermeasures.

Part of the DOD’s research to develop new medical countermeasures is conducted by the Defense Advanced Research Projects Agency (DARPA), an agency best known for its involvement in the creation of what we now call the Internet. DARPA was created in 1958 “to formulate and execute R&D projects that would expand the frontiers of technology beyond the immediate and specific requirements of the Military Services and their laboratories.”

DARPA’s Microphysiological Systems (MPS) program was created for the purpose of developing a rapid technology for assessing the human safety and effectiveness of new medical countermeasures so that they can quickly be moved into human trials. This program plans to develop a testing platform using engineered human tissues (3D cell cultures) that replicate human physiological systems and correctly predicts the safety and efficacy of new drugs and vaccines. The goal is to develop a testing platform of interconnected human tissues representing key physiological systems that can be validated for regulatory testing of drugs, vaccines, and biologics.

The development of the new DARPA testing platform “should increase the quality and potentially the number of novel therapies that move through the pipeline and into clinical care.” Drug toxicity, even after regulatory approval and marketing, remains a major cause of new drug attrition. Pharmaceutical companies currently rely on high-content human cell screening assays to weed out a large number of toxic or ineffective drug candidates. The remaining drug candidates are then subjected to a series of animal studies required to satisfy regulatory requirements. Neither the cell-based assays or the animal studies, nor the combined methods, provides a perfect prediction of safety and efficacy, sometimes resulting in previously approved drugs being removed from the market after causing human injuries and deaths.

The MPS program is working collaboratively with the National Institutes of Health (NIH) and the Food and Drug Administration (FDA) to develop this innovative new technology.

On September 16, 2011, President Obama signed new patent reform legislation, the America Invents Act. At the same time he announced additional initiatives to “move ideas from lab to market.” One of these initiatives will be the launch of the NIH National Center for Advancing Translational Sciences (NCATS). NCATS will work with the biotechnology industry and entrepreneurs to develop new tools and methods to reduce the time and costs of getting new drugs and diagnostics from discovery in the laboratory into medical use. However, Congressional funding for NCATS has not been finalized.

One proposed NCATS activity will be coordination of NIH efforts with the DARPA program. The DARPA and NIH programs will work collaboratively, but will remain independent. DARPA research will focus on development of the testing platform and the cell-based models and providing proof-of-concept; NCATS research will develop complementary microphysiological systems. Both will be coordinating their efforts with the FDA to ensure regulatory issues are taken into consideration.

NIH and DARPA will solicit proposals this year from researchers in industry, academia, government, and other research organizations for the development of the proposed technologies. Each organization will commit around $70 million dollars over the next 5 years to their respective programs and funded research.

The DARPA Broad Agency Announcement (DARPA-BAA-11-73) for the development of “innovative research proposals to develop an in vitro platform of human tissue constructs that accurately predicts the safety, efficacy, and pharmacokinetics of drug/vaccine candidates prior to their first use in man” was published on September 15, 2011. Specifically excluded is research that primarily results in evolutionary improvements to the existing state of practice. Multiple awards are anticipated, and all types of organizations, except for government and federally-funded labs, are eligible to apply.

Abstracts are due October 27, 2011

; full proposals due December 12, 2011.

Proposals to the DARPA research program must describe the development of an innovative platform of human tissues based on 3-dimensional cell constructs that accurately replicates human physiological systems, especially with respect to drug and vaccine effects. Specific organs and physiological systems that must be represented on this testing platform include: circulatory, endocrine, gastrointestinal, immune, integumentary, musculoskeletal, nervous, reproductive, respiratory, and urinary. The different tissue systems should be capable of interacting with one another and remain viable for up to four weeks. Certain parameters and data that will be needed to validate the in vitro models and the platform must be described. The use of the platform for in vitro infectious disease detection is an optional component.

NIH funding will be through the NIH Common Fund. Proposals to the 2012 NIH Director’s Transformative Research Awards are due January 12, 2012. This is the same type of award as the $6 million NIH grant recently awarded to Dr. Thomas Hartung of the Johns Hopkins Center for Alternatives to Animal Testing (CAAT) for his proposed research to map cellular toxicity pathways.