Impulse Oscillometry Endpoint Sensitivity to Regional Lung Function Changes using Computational Fluid Dynamics (CFD) (U01) Clinical Trial Required | RFA FD 21 020

Opportunity Information: Apply for RFA FD 21 020

This grant opportunity, titled "Impulse Oscillometry Endpoint Sensitivity to Regional Lung Function Changes using Computational Fluid Dynamics (CFD) (U01) Clinical Trial Required," is a cooperative agreement from the U.S. Department of Health and Human Services, Food and Drug Administration (FDA). It focuses on improving how lung function is measured in studies that compare generic orally inhaled drug products (OIDPs) to their reference (brand) products. The central idea is that standard spirometry endpoints, especially forced expiratory volume in 1 second (FEV1), may not always be sensitive enough to detect meaningful differences in airway function for certain products or patient populations, and that impulse oscillometry (IOS) might provide endpoints that pick up subtler or more region-specific changes.

The scientific premise behind the funding is that IOS measures respiratory mechanics using small pressure oscillations (sound waves) delivered into the airways during normal breathing, which means it does not rely heavily on patient effort or coordination the way spirometry does. Because IOS can capture information about airway resistance and reactance across different frequencies, it has the potential to reflect changes in different airway regions (including smaller or more peripheral airways) that might not be well captured by FEV1. For generic OIDPs, where regulators and developers need robust tools to compare a proposed generic product against a reference product, a more sensitive clinical endpoint could help strengthen or streamline comparative evaluations when traditional spirometric measures are less discriminating.

The project described in the announcement has two linked components that are meant to inform each other. First, the award supports a small in vivo clinical study (a clinical trial is required) in which participants receive an orally inhaled drug product and lung function is assessed using both IOS endpoints and spirometry endpoints. The goal is to quantify treatment effects and directly observe how IOS measurements respond relative to conventional spirometry measures like FEV1. Second, the project requires concurrent development of a computational fluid dynamics (CFD) model. This CFD work is intended to provide a mechanistic framework for interpreting IOS signals by connecting airflow patterns, airway geometry, and regional lung function changes to the IOS endpoints observed in the clinical study. In practical terms, the modeling is meant to help explain when and why IOS may detect differences, and how those differences relate to deposition, airway caliber changes, or other physiologic factors relevant to inhaled therapies.

From a regulatory science perspective, the combined clinical and modeling approach is aimed at determining the applicability and usefulness of IOS endpoints for generic product comparison. If IOS endpoints can be shown to be reliably more sensitive than FEV1 in certain contexts, and if CFD can clarify what those endpoints mean physiologically and regionally, the output could support better study designs and more informative endpoint selection for future generic OIDP assessments. The emphasis is not simply on generating another dataset, but on building evidence and tools that improve interpretation and decision-making around equivalence or comparative performance.

Administratively, this is a discretionary funding opportunity using the cooperative agreement mechanism (U01), which typically implies substantial scientific or programmatic involvement from the funding agency during the project. The funding opportunity number is RFA-FD-21-020 and it is listed under CFDA 93.103. The maximum award amount (ceiling) is $1,000,000, and the FDA anticipated making one award. Eligibility is broad and includes many types of applicants, such as state, county, and local governments; public and private institutions of higher education; tribal governments and tribal organizations; nonprofit organizations (with or without 501(c)(3) status); for-profit organizations (other than small businesses); small businesses; public housing authorities; and other entities as described in the opportunity’s eligibility notes. The opportunity was created on February 22, 2021, with an original closing date of April 26, 2021.

Overall, the opportunity is designed to test whether IOS can serve as a more sensitive, clinically meaningful endpoint than FEV1 for detecting treatment-related differences in lung function, while using CFD modeling to connect those measurements to regional airway and lung mechanics. The intended deliverable is not just a one-off clinical comparison, but a stronger scientific basis for using IOS endpoints in the evaluation of generic inhaled drugs alongside established spirometry measures.

• The Department of Health and Human Services, Food and Drug Administration in the consumer protection, food and nutrition, science and technology and other research and development sector is offering a public funding opportunity titled "Impulse Oscillometry Endpoint Sensitivity to Regional Lung Function Changes using Computational Fluid Dynamics (CFD) (U01) Clinical Trial Required" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.103.
• This funding opportunity was created on Feb 22, 2021.
• Applicants must submit their applications by Apr 26, 2021. (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.
• The number of recipients for this funding is limited to 1 candidate(s).
• 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 (see text field entitled Additional Information on Eligibility for clarification).

Apply for RFA FD 21 020

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