The National Institutes of Health (NIH) announced the launch of the Complement Animal Research In Experimentation program with more than $150 million in research funding to develop and scale research methods that better simulate human biology. The funding marks the first awards under the Complement-ARIE program, an initiative to develop, implement, and standardize lab or computer-based methods, also known as new approach methodologies (NAMs). Research teams across the United States will lead projects designed to produce more predictive models of human disease.

The program will establish technology development centers (TDCs) to facilitate NAM development in the areas of greatest scientific and regulatory need. Examples include NAMs technologies to study gynecological disorders, cardiac disease, neurological disorders, rare diseases, and more. A NAMs data hub and coordinating center (NDHCC) will facilitate data sharing and standards development, while a validation and qualification network (VQN) will leverage a public-private partnership with industry and regulatory expertise necessary to implement reliable, marketable NAMs.

Technology Development Centers (TDCs): The TDCs aim to support the development of NAMs using multiple methods to address questions about human biology and disease. TDCs will have built-in training and outreach components to ensure that NAMs can be adopted and deployed in the future by an informed and engaged research workforce. While most of the Complement-ARIE program is supported by the NIH Common Fund, other NIH partners like the Division of Program Coordination, Planning, and Strategic Initiatives (DPCPSI) and Office of Research on Women’s Health (ORWH) generously provided additional funding for one of the TDCs.

• A TDC at Massachusetts Institute of Technology, Cambridge, aims to facilitate drug development for gynecological disorders by preparing NAM technologies for rigorous regulatory requirements, increasing their relevance to human physiology with clinical data and deploying them in pre-clinical use cases. This center will be led by Linda Griffith, Ph.D., and has received over $4.7 million in co-funding from ORWH.
• A TDC at Johns Hopkins University, Baltimore, seeks to produce human cell- and electronics-based brain organoids capable of simulating learning and memory processes that will allow for the testing of potential drugs for Alzheimer’s disease and neurodevelopmental disorders on the benchtop. This center will be led by Lena Smirnova, Ph.D.
• A TDC at NIH’s National Center for Advancing Translational Sciences (NCATS) will create several lab and computer-based models to provide a comprehensive, multiorgan model of scarred, or fibrotic, tissue. The models will serve as a platform for studying and exploring therapies for both common and rare diseases wherein fibrosis plays a key role. The center will be led by Marc Ferrer, Ph.D.
• A TDC at Texas A&M AgriLife Research, College Station, means to integrate NAMs into established methods of evaluating the toxicity of similar chemicals in consumer products, accelerating chemical evaluations and reducing reliance on animal testing. This center will be led by Ivan Rusyn, M.D., Ph.D.
• A TDC at Cincinnati Children's Hospital Medical Center will apply its clinical, computational and experimental expertise to develop combinatorial, patient-specific NAMs to model gastrointestinal diseases and facilitate drug discovery. This center will be led by James M. Wells, Ph.D.
• A TDC at Stanford University, Palo Alto, will bring together experts in AI, bioinformatics and biomaterials to develop organoid models for cardiac disease that reproduce conditions unique to specific patients. This center will be led by Joseph C. Wu, M.D., Ph.D.
• A TDC at Brigham and Women’s Hospital, Boston, intends to establish bioengineered systems that replicate musculoskeletal structure, function and pathology to provide an in vitro testbed for musculoskeletal disorders. This center will be led by Shrike Zhang, Ph.D.

NAMs Data Hub and Coordinating Center (NDHCC): The NDHCC will integrate NAMs-relevant data structures via a central data hub and will help to develop and apply standards for data reporting and model credibility. The NDHCC will prioritize adherence to findable, accessible, interoperable, and reusable (FAIR) data principles. 

• An NDHCC at the New York University School of Medicine plans to build an interoperable data ecosystem that will enable dissemination of NAMs information, broadly accelerating the development and adoption of these new technologies. The center will be led by Gustavo Stolovitsky, Ph.D. 

These extensive efforts by the Complement-ARIE program are happening at a time when NIH and other federal agencies have identified the potential of NAMs to improve human health and are moving to accelerate their deployment. The FDA announced a roadmap and draft guidance to reduce animal testing in preclinical safety studies and the EPA is prioritizing ongoing efforts to develop and use NAMs to test chemicals for health effects. Through these combined federal efforts, NAMs are poised to more efficiently support the development and approval of new treatments and catalyze advances in health and disease research through human-based solutions.