Translational Centers for Microphysiological Systems (TraCe MPS) (U2C Clinical Trials Not Allowed)

Background
The purpose of this funding opportunity announcement (FOA) is to establish Centers to support research that will accelerate the translational use of Microphysiological Systems (MPS) in drug development through regulatory acceptance and adoption for industrial use, by establishing MPS that are fit-for-purpose for industry needs and have specific defined contexts of use (CoUs). These Centers will further the development of MPS as drug development tools (DDTs) that, once qualified, will be made publicly and commercially available to fill unmet needs in drug development.

Grant Details
More than 90% of the drugs being developed fail due to unpredicted clinical toxicity or lack of efficacy in the clinic. While current approaches using in vitro 2-D cell assays and/or in vivo animal models during pre-clinical drug development have established value to biomedical research, they also have limitations in being able to reliably predict human physiological responses to various perturbations, contributing to the high attrition rate in drug development. Microphysiological systems (MPS) hold promise to overcome some of these limitations as one of the New Approach Methodologies (NAMs). The NIH, led by NCATS, developed the MPS or Tissue Chips for Drug Screening program to address translational problems in drug development through a series of proof-of concept initiatives aimed at use of MPS for improving safety pharmacology studies, developing MPS as disease models for efficacy studies, and paving the way towards precision medicine using MPS to inform clinical studies and trial designs. The initial MPS program was a five-year partnership among NIH, DARPA and FDA, to support the development and integration of bioengineered multi-organ systems, and the generation of renewable human cell resources for predictive assessment of drug safety and toxicity. MPS disease models established the use of MPS to recreate disease phenotypes and test candidate therapeutics on them. More recently, RFA-TR-19-014 was aimed towards use of MPS in precision medicine to provide empirical support regarding the intervention's safety and efficacy, and the mechanism that underlies clinical benefit. The technology development path, including for MPS, is commonly non-linear, and many programs stop at the proof-of-concept stage. A key factor to a linear technology development pathway is to define the value proposition, to promptly transition from an R&D-only stage to the qualification phase, and finally move to optimization and scale-up for rapid adoption.

Eligibility Requirements
Eligible applicants include higher education institutions, nonprofits with 501(c)(3) IRS status (other than institutions of higher education), for-profit organizations (including small businesses), state governments, county governments, city or township governments, special district governments, Indian/Native American tribal governments (federally recognized), Indian/Native American tribal governments (other than federally recognized), U.S. territory or possession agencies or other components as specified in Section III. Eligibility Information.

Period of Performance
The period of performance is expected to be 5 years.

Grant Value
The National Center for Advancing Translational Sciences (NCATS) intends to commit $4M per year to fund 2-4 awards. The National Cancer Institute (NCI) intends to commit $12M per year to fund 5-8 awards. The National Institute on Aging (NIA) intends to commit $3.5M in FY24 to fund 2 awards.