Population Pharmacokinetic Modeling of Systemic Pharmacokinetic Data to Inform Bioequivalence in Regional Lung Exposure (U01) Clinical Trial Not Allowed | RFA FD 23 017

Opportunity Information: Apply for RFA FD 23 017

The Food and Drug Administration (FDA) offered this cooperative agreement opportunity, titled "Population Pharmacokinetic Modeling of Systemic Pharmacokinetic Data to Inform Bioequivalence in Regional Lung Exposure (U01) Clinical Trial Not Allowed" (RFA-FD-23-017), to support research that could improve how bioequivalence (BE) is demonstrated for orally inhaled drug products (OIDPs). OIDPs are not just drugs; they are drug-device combination products, which makes them harder to evaluate than many traditional dosage forms. For locally acting inhaled products, the key scientific problem is that the therapeutic effect is intended to occur primarily in the lungs, yet it is often difficult to directly measure local lung exposure in a way that is practical, sensitive, and acceptable for routine BE assessments.

The grant focuses on a specific regulatory and scientific gap: the current FDA "weight-of-evidence" approach for establishing BE for locally acting OIDPs typically combines multiple lines of evidence, including in vitro BE testing, in vivo systemic pharmacokinetic (PK) studies, and either comparative clinical endpoint (CCEP) studies or pharmacodynamic (PD) studies, alongside expectations around formulation sameness and device similarity. However, for some inhaled products, CCEP and PD studies can be problematic because they may not be sensitive enough to detect meaningful formulation differences. In other words, even if two products differ in ways that could matter for performance in the lungs, a clinical endpoint study or available PD measure may fail to reliably pick up those differences, making such studies costly and burdensome without necessarily improving decision-making.

The purpose of this funding opportunity is to back modeling and simulation research that tests whether systemic PK concentration data, when analyzed using population pharmacokinetic (PopPK) approaches, can be leveraged to infer or help assess formulation differences in regional lung exposure. The core idea is to investigate feasibility: can researchers use information in the systemic concentration-time profile, together with mechanistic or semi-mechanistic PK models and population-level variability modeling, to distinguish differences in where and how much drug deposits in the lung (for example, different lung regions) for OIDPs with varying drug and product characteristics? The opportunity is aimed at exploring this question across different types of inhaled drugs and device/product properties, rather than assuming one method will work universally.

This is a U01 cooperative agreement, meaning FDA expects to have substantial involvement in the project compared with a standard grant mechanism. The opportunity is explicitly "Clinical Trial Not Allowed," signaling that the supported work should not be structured as a clinical trial as defined by NIH/FDA grant policy; instead, the emphasis is on modeling, simulation, and analysis of systemic PK data (which may involve secondary data use or non-trial study designs consistent with the funding rules). The activity category is listed broadly under consumer protection and science/technology research and development, reflecting FDA's mission to support regulatory science that can lead to better, more efficient standards for product evaluation.

In terms of who could apply, eligibility was broad and included higher education institutions (public/state and private), nonprofits (with or without 501(c)(3) status), for-profit organizations (including small businesses and other for-profits), and a wide range of government entities (state, county, city/township, special districts, independent school districts), as well as tribal governments and tribal organizations, U.S. territories/possessions, public housing authorities/Indian housing authorities, faith-based/community-based organizations, regional organizations, and non-U.S. (foreign) entities. The announcement also noted that certain institution types were encouraged to apply, including Hispanic-serving institutions, HBCUs, tribally controlled colleges and universities, Alaska Native and Native Hawaiian-serving institutions, and AANAPISIs, consistent with FDA's interest in broad participation across the research community.

Key administrative details from the source information include: the agency is the FDA; the funding instrument is a cooperative agreement; the CFDA number is 93.103; the opportunity category is discretionary; and the original closing date was February 28, 2023 (with a creation date of December 1, 2022). The listed award ceiling was $500,000. The number of expected awards was not clearly specified in the provided text (it appears blank), so applicants would have needed to consult the full notice for any clarifications on anticipated funding volume or number of projects.

Overall, this opportunity is best understood as a targeted regulatory-science effort to see whether advanced PopPK modeling of systemic PK data can help bridge a longstanding challenge in inhalation product equivalence: demonstrating that two locally acting inhaled products deliver similar drug exposure to relevant regions of the lung, especially in cases where traditional clinical endpoint or PD approaches are insensitive, impractical, or inefficient. The long-term regulatory value, if the research is successful, would be to strengthen or possibly streamline BE strategies for certain OIDPs by providing evidence-based modeling frameworks that connect systemic PK measurements to conclusions about regional lung exposure and formulation performance.

• The Food and Drug Administration in the consumer protection, science and technology and other research and development sector is offering a public funding opportunity titled "Population Pharmacokinetic Modeling of Systemic Pharmacokinetic Data to Inform Bioequivalence in Regional Lung Exposure (U01) Clinical Trial Not Allowed" 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 2022-12-01.
• Applicants must submit their applications by 2023-02-28. (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 $500,000.00 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.

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