Quantify the expression of metabolizing enzymes and transporter proteins in lung, eye and skin tissue in relevant animal models and humans (U01) Clinical Trial Not Allowed | RFA FD 21 018

Opportunity Information: Apply for RFA FD 21 018

This funding opportunity (RFA FD 21 018) is a U01 cooperative agreement from the U.S. Department of Health and Human Services, Food and Drug Administration (FDA), focused on generating high-quality, quantitative tissue data that can strengthen drug development and regulatory decision-making for locally acting drug products. The central goal is to systematically measure, at the protein level, the presence and abundance of drug-metabolizing enzymes and transporter proteins in key barrier and target tissues: eye, lung, and skin. The work is designed to be highly practical and translational, meaning the resulting measurements are not intended to sit in isolation as descriptive biology, but to be built directly into existing mechanistic modeling platforms so that researchers and regulators can better predict drug exposure and support virtual bioequivalence assessments. Clinical trials are not allowed under this announcement, which signals that the program is aimed at laboratory, ex vivo, and modeling work rather than prospective interventional studies in human participants.

Applicants are expected to choose one of three research tracks and focus their proposal accordingly: ophthalmic, dermal, or pulmonary. For the ophthalmic area, the emphasis is on quantifying metabolizing enzymes and transporter proteins in rabbit and human eye tissues. For the pulmonary area, the emphasis is on human lung tissue, and for the dermal area, the emphasis is on human skin tissue. The repeated theme across all three tracks is systematic protein quantification using the most advanced techniques available, which typically implies modern, sensitive proteomics approaches that can provide reproducible absolute or relative protein abundance across tissue regions and relevant cell types. By focusing on protein expression (rather than only gene expression), the project aims to capture information that is more directly linked to functional metabolism and transport, which is essential for predicting local and systemic drug concentrations.

A major deliverable implied by the announcement is the integration of experimentally generated tissue expression data into modeling tools used for pharmacokinetics and bioequivalence evaluation. The stated intent is to enable virtual bioequivalence assessments both locally (at the site of action, such as ocular tissues, the lung, or the skin) and systemically (circulating exposure), and to do so not only for the parent drug but also for any pharmacologically active metabolite. In practical terms, the program is trying to close a known evidence gap: for many locally acting products, it is difficult to measure drug levels directly at the target site in humans, so regulators and developers rely increasingly on mechanistic models. Those models can only be as credible as the biological parameters they are built on, and enzyme/transporter abundance is a key set of parameters controlling absorption, distribution, metabolism, and clearance in these tissues.

The mechanism is a cooperative agreement (U01), which generally means substantial scientific involvement from the FDA beyond what is typical for a standard grant. That often includes coordination on technical approaches, harmonization of methods so data can be compared across projects, and alignment on how outputs should be formatted or incorporated into agency-relevant modeling frameworks. The announcement anticipates up to five awards, with an award ceiling of $850,000, indicating support for multiple groups working in parallel, likely one or more per tissue area, to produce a broader data resource rather than a single isolated dataset.

Eligibility is broad and includes many types of domestic entities such as state, local, and tribal governments; public and private institutions of higher education; nonprofits (with or without 501(c)(3) status); for-profit organizations (including small businesses); and other categories as clarified in the full eligibility text. The program sits within FDA-related research and development priorities under CFDA 93.103, and is categorized under science and technology as well as consumer protection/food and nutrition, reflecting FDA's mission to ensure safe and effective medical products and to modernize the scientific standards used in product evaluation.

Key administrative details from the notice include a creation date of January 7, 2021, and an original closing date of March 15, 2021. Overall, the opportunity is best understood as an effort to build foundational quantitative biology datasets for eye, lung, or skin that can be plugged into computational pharmacokinetic and bioequivalence models, improving the credibility of virtual BE approaches for locally acting products and supporting evaluation of both parent drugs and active metabolites without conducting clinical trials.

• 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 "Quantify the expression of metabolizing enzymes and transporter proteins in lung, eye and skin tissue in relevant animal models and humans (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 Jan 07, 2021.
• Applicants must submit their applications by Mar 15, 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 $850,000.00 in funding.
• The number of recipients for this funding is limited to 5 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 21 018

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