BRAIN Initiative: Next-Generation Invasive Devices for Recording and Modulation in the Human Central Nervous System (UG3/UH3 Clinical Trial Optional) | RFA NS 21 023

Opportunity Information: Apply for RFA NS 21 023

The NIH BRAIN Initiative funding opportunity titled "Next-Generation Invasive Devices for Recording and Modulation in the Human Central Nervous System (UG3/UH3 Clinical Trial Optional)" (RFA-NS-21-023) is designed to push promising invasive neurotechnology closer to real-world use in people. The central goal is to support translational work that advances therapeutic and diagnostic devices for conditions affecting the nervous system or neuromuscular system, especially where the technology is novel enough that key questions about performance, function, or final design cannot realistically be answered through additional benchtop testing or animal studies alone. In practice, this program is meant to help teams bridge the gap between an advanced prototype and early clinical experience in humans, with a strong focus on evidence, safety, and practical readiness for clinical use.

The scope of supported work covers the kinds of activities that typically sit between academic proof-of-concept and broader clinical adoption. Projects can include building and implementing clinical prototype devices, running non-clinical safety and efficacy studies, and completing design verification and validation steps that regulators and clinical partners expect before a device is tested in people. The FOA also supports the process of obtaining an Investigational Device Exemption (IDE) for a Significant Risk study, which is a key FDA regulatory pathway when a device poses potential serious risk and is being studied in humans. Importantly, the FOA anticipates that many projects will culminate in a small clinical study, not necessarily to prove definitive clinical benefit, but to generate practical, decision-driving information about device performance, usability, recording/modulation capabilities, safety signals, or design refinements that are difficult to obtain non-clinically due to the device's novelty or intended use. The "Clinical Trial Optional" framing signals that a clinical study may be included when justified, but the program is fundamentally structured around translation and readiness milestones, not purely exploratory research.

This is a milestone-driven cooperative agreement using the UG3/UH3 phased award mechanism. The UG3 phase typically functions as an initial, time-limited stage focused on completing defined preparatory and risk-reduction activities, such as finalizing the prototype for clinical use, completing required non-clinical testing, establishing manufacturing/quality or reliability processes as needed, and preparing the IDE package. If the UG3 milestones are met, the project can transition to the UH3 phase, which commonly supports execution of the next stage, often including the small clinical study and any remaining validation activities. Because this is a cooperative agreement, NIH program staff are expected to play an active role beyond standard grant administration. That includes negotiating the final project plan before award, agreeing on milestones and go/no-go criteria, and monitoring progress closely during the project to ensure that deliverables align with the translational intent of the program.

Eligibility is broad across many U.S.-based organization types, reflecting NIH's interest in supporting cross-sector device development teams. Eligible applicants include state, county, and local governments; special districts; independent school districts; public and state-controlled colleges and universities; private institutions of higher education; federally recognized tribal governments; tribal organizations that are not federally recognized; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status; for-profit organizations (other than small businesses) as well as small businesses; and other categories. The FOA also explicitly notes additional eligible applicant types such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), faith-based or community-based organizations, eligible federal agencies, regional organizations, tribal governments that are not federally recognized, and U.S. territories or possessions. Foreign institutions are not eligible to apply, and non-U.S. components of U.S. organizations are not eligible to apply. However, foreign components, as defined in the NIH Grants Policy Statement, are allowed, which typically means certain discrete international elements can be included when well-justified and compliant with NIH policy, even though the applicant organization itself must be domestic.

From an administrative standpoint, the funding instrument is a cooperative agreement under a discretionary opportunity category, and it falls under health-related federal assistance (with multiple CFDA/assistance listing numbers associated with NIH neuroscience and related programs). The listed award ceiling is $1,000,000, and the original closing date for the referenced competition was February 20, 2024. Overall, this FOA is best understood as a structured, NIH-partnered pathway for teams working on invasive human CNS recording and modulation devices to complete the last major preclinical-to-clinical steps, secure the regulatory groundwork for a significant risk study when applicable, and generate early human data that meaningfully informs device design and function.

• The National Institutes of Health in the education, health, income security and social services sector is offering a public funding opportunity titled "BRAIN Initiative: Next-Generation Invasive Devices for Recording and Modulation in the Human Central Nervous System (UG3/UH3 Clinical Trial Optional)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.173, 93.213, 93.242, 93.273, 93.279, 93.286, 93.853, 93.865, 93.866, 93.867.
• This funding opportunity was created on 2021-05-07.
• Applicants must submit their applications by 2024-02-20. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $1,000,000.00 in funding.
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for RFA NS 21 023

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