Opportunity Information: Apply for RFA FD 18 012
The FDA funding opportunity "Bioequivalence of Topical Products: Evaluating the Cutaneous Pharmacokinetics of Topical Drug Products Using Non-Invasive Techniques (U01)" is aimed at solving a long-standing problem in generic topical drug development: proving bioequivalence (BE) in a way that is accurate, sensitive, reproducible, and practical. For many drugs that act systemically, BE can be shown by comparing plasma pharmacokinetics (PK), which regulators view as a strong and efficient standard. Topical products are different because the drug is intended to act locally in skin tissue, and measuring drug levels at the site of action (typically the epidermis and sometimes the dermis) is far more difficult than drawing blood and running standard PK analyses. While an in vitro pathway exists through in vitro permeation testing (IVPT) using excised human skin in diffusion cells, there is still no broadly established in vivo cutaneous PK method that regulators can rely on for topical BE, and that gap slows down generic development and keeps clinical endpoint studies in play for many products.
The central objective of this cooperative agreement is to support the development of non-invasive spectroscopic and imaging-based approaches that can monitor and compare how much drug gets into the skin over time after topical application, effectively generating cutaneous PK profiles. The goal is not just to create attractive images, but to build a method that can quantify or at least semi-quantify the rate and extent of drug availability at or near the therapeutic target within skin. The program is meant to advance both the underlying science (how these optical or spectroscopic signals behave in skin, what can realistically be measured, and under what conditions) and the practical study designs needed to evaluate BE between a test generic and a reference listed drug (RLD) or reference standard (RS). The end state the FDA is pushing toward is a technique that could ultimately be used with commercially available topical products in human subjects, without needing invasive sampling or drug modification.
A major theme running through the opportunity is overcoming technical barriers that currently prevent imaging or spectroscopy from serving as dependable PK tools in skin. Skin itself produces signal interference that can mask or distort the signal from a drug, so applicants are expected to develop strategies to separate drug signal from background tissue signal and to calibrate signal intensity in a way that supports comparisons between products. The FDA highlights that approaches relying on chemical modification of the active ingredient, such as deuteration, are generally misaligned with the practical regulatory goal because BE needs to be demonstrated for the marketed, commercially formulated drug products as they are actually sold and used. Another challenge the solicitation calls out is depth: as measurements go deeper into skin, signal attenuation typically increases, so the program seeks methods that can either accurately measure at meaningful depths (epidermis and possibly dermis) or provide correction strategies that account for depth-related signal loss. Related to this is the desire to learn whether a given technology can provide not just total signal but meaningful information about drug distribution and localization within layers of skin, since where the drug resides can matter as much as how much is present.
The research scope is intentionally broad on the technology side, but tightly focused on demonstrating BE-relevant performance. Proposed work is expected to identify or develop non-invasive techniques (for example, spectroscopy, imaging, or tomography-based methods) that are accurate, sensitive, and reproducible for characterizing cutaneous PK after topical dosing. Applicants are expected to think through practical measurement issues such as temporal resolution (how frequently you can measure changes over time), spatial resolution (how finely you can map drug presence across an area), and the orientation and size of the measurement region (since topical application is inherently heterogeneous). The program also expects teams to define the limitations of their selected methods, including which drug chemistries are measurable with a given modality, which formulations might cause interference, and when a method can only provide semi-quantitative rather than fully quantitative outputs. In other words, part of success is clearly delineating what the method can and cannot do, and then building a convincing proof-of-principle around realistic use cases.
A defining feature of the opportunity is that it is a U01 cooperative agreement, meaning substantial FDA scientific involvement is built into the project. The awardee is expected to work collaboratively with FDA scientists to refine the research plan, align study designs and protocols with regulatory needs, coordinate study conduct, analyze the resulting data, and publish findings. The multi-year structure is deliberate because the FDA anticipates that meaningful progress will require technology development, extensive characterization, and multiple iterative studies rather than a single experiment. Drugs and product sets are to be selected in collaboration with the FDA, and may include cases where clinical endpoint BE studies already exist, as well as sets that can serve as positive controls (products believed to be bioequivalent) and negative controls (products expected not to be bioequivalent). That control framework is important because the program is not simply about detecting drug in skin; it is about demonstrating that the method can reliably show BE when BE is truly present and, just as importantly, can discriminate when BE is not present.
The deliverable the FDA is implicitly driving toward is a non-invasive cutaneous PK methodology that can generate time-course profiles from which meaningful PK endpoints could be derived and used in BE comparisons. The funded research should produce proof-of-principle results that demonstrate discrimination sensitivity (the ability to detect real differences between products when they exist) and reproducibility (the ability to get consistent results across repeats, subjects, sites, and time). The FDA also signals an interest in cross-validation across groups and technologies: FDA collaborators may ask independent research teams to align key study parameters like products, dose amount, and dose duration so results from different non-invasive techniques can be compared or corroborated. In practical terms, the opportunity is designed to move the field closer to a regulatory-usable in vivo approach for topical BE, reducing reliance on expensive and variable clinical endpoint trials and enabling more efficient development and approval of generic topical medicines.
From an administrative standpoint, this opportunity (RFA-FD-18-012) is offered by the Department of Health and Human Services, Food and Drug Administration, under a cooperative agreement funding instrument. The program listed an award ceiling of $250,000 and anticipated making two awards. Eligibility is broad, spanning government entities, tribal organizations, public and private higher education institutions, nonprofits (with and without 501(c)(3) status), for-profit organizations (including small businesses), which reflects the FDA's intent to attract a mix of academic laboratories, technology developers, and applied research groups capable of both engineering development and rigorous bioanalytical validation. Although the original closing date was June 4, 2018, the scientific framing remains a clear snapshot of what the FDA views as the key hurdles and the kinds of evidence needed to turn non-invasive skin measurements into a credible, BE-focused tool for topical drug products.Apply for RFA FD 18 012
- The Department of Health and Human Services, Food and Drug Administration in the agriculture, consumer protection, food and nutrition sector is offering a public funding opportunity titled "Bioequivalence of Topical Products: Evaluating the Cutaneous Pharmacokinetics of Topical Drug Products Using Non-Invasive Techniques (U01)" 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 Mar 23, 2018.
- Applicants must submit their applications by Jun 04, 2018. (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 $250,000.00 in funding.
- The number of recipients for this funding is limited to 2 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.
[Watch] Creating a grant proposal using the step-by-step wizard inside the applicant portal:
Frequently Asked Questions (FAQs)
1) What is the focus of this FDA funding opportunity?
The opportunity focuses on developing and evaluating non-invasive spectroscopy and imaging-based methods that can measure how a topical drug gets into the skin over time. The aim is to generate cutaneous pharmacokinetic (PK) profiles that can be used to support bioequivalence (BE) comparisons between a proposed generic topical product and a reference listed drug (RLD) or reference standard (RS).
2) What problem is this program trying to solve in generic topical drug development?
It targets a long-standing challenge: proving BE for topical products in a way that is accurate, sensitive, reproducible, and practical. Unlike systemically acting drugs where plasma PK is often a strong and efficient BE standard, topical drugs act locally in skin tissue, making drug levels at the site of action much harder to measure. This gap contributes to continued reliance on clinical endpoint studies for many topical products.
3) Why is plasma pharmacokinetics not enough for topical bioequivalence?
Plasma PK works well when the drug effect is tied to systemic exposure. For many topical products, the intended action is local within skin (typically epidermis and sometimes dermis). Blood measurements may not reflect drug availability at the local therapeutic target in skin, so the program is geared toward methods that assess drug in skin directly (non-invasively).
4) What types of non-invasive technologies does the FDA want to support?
The scope is broad, including spectroscopic, imaging, and tomography-based approaches, as long as they can credibly characterize cutaneous PK after topical dosing in a BE-relevant way. The emphasis is less about producing visually compelling images and more about generating data that can quantify or semi-quantify the rate and extent of drug availability in skin over time.
5) What does "cutaneous pharmacokinetics" mean in this context?
It refers to measuring how much drug is present in skin and how that level changes over time after topical application, ideally in or near the therapeutic target layers (epidermis and possibly dermis). The intent is to produce time-course profiles that could support derivation of meaningful PK endpoints for BE comparisons.
6) Is this opportunity about in vitro permeation testing (IVPT)?
IVPT using excised human skin in diffusion cells is mentioned as an existing in vitro pathway, but the core gap highlighted here is the lack of a broadly established in vivo, non-invasive cutaneous PK method that regulators can rely on for topical BE. This program is centered on advancing in vivo non-invasive measurement approaches.
7) What key performance characteristics are expected from proposed methods?
Methods are expected to be accurate, sensitive, and reproducible for characterizing cutaneous PK following topical dosing. The FDA is looking for proof-of-principle evidence that a technique can produce BE-relevant outputs and function reliably in realistic study conditions.
8) Why is separating drug signal from skin background signal such a major theme?
Skin produces its own signals that can interfere with, mask, or distort the signal attributable to the drug. Applicants are expected to develop strategies to distinguish drug signal from tissue background and to calibrate signal intensity so that comparisons between products are scientifically defensible.
9) What does the FDA say about chemically modifying the active ingredient (for example, deuteration)?
The FDA indicates that approaches relying on chemical modification of the active ingredient (such as deuteration) are generally misaligned with the regulatory goal. The purpose of BE testing is to demonstrate equivalence for marketed, commercially formulated drug products as they are sold and used, without modifying the drug.
10) What depth of skin is the program most concerned with measuring?
The target is typically the epidermis and, for some products, potentially the dermis. Depth is a technical challenge because optical/spectroscopic signals often attenuate as measurement depth increases. The program encourages either methods that can measure at meaningful depths or correction strategies that address depth-related signal loss.
11) Does the program care about where the drug is located within the skin layers, not just how much drug is present?
Yes. The FDA signals interest in whether a technology can provide information about drug distribution and localization within skin layers, because location can matter as much as total amount in determining local availability at or near the therapeutic target.
12) What practical measurement issues should applicants consider?
The opportunity calls out considerations such as temporal resolution (how frequently changes can be measured over time), spatial resolution (how finely drug presence can be mapped across an area), and the orientation/size of the measurement region. These issues matter because topical application and skin exposure can be heterogeneous.
13) Are applicants expected to state the limitations of their chosen technique?
Yes. A strong application is expected to clearly define what the method can and cannot do, including which drug chemistries are measurable, which formulations may cause interference, and when outputs are semi-quantitative rather than fully quantitative.
14) What makes this a U01 cooperative agreement rather than a typical grant?
A U01 includes substantial FDA scientific involvement. Awardees are expected to collaborate with FDA scientists to refine research plans, align study designs and protocols with regulatory needs, coordinate study conduct, analyze data, and publish findings. It is designed as a collaborative, iterative effort.
15) Why does the opportunity emphasize multi-year, iterative work?
The FDA anticipates that meaningful progress will require technology development, extensive characterization, and multiple iterative studies rather than a single experiment. The goal is a method that moves toward regulatory usability, which generally demands robust evidence and repeatable performance.
16) How will drugs and product sets be selected for the studies?
Drugs and product sets are to be selected in collaboration with the FDA. The solicitation indicates that selections may include products where clinical endpoint BE studies already exist, as well as product sets that can act as positive controls (believed BE) and negative controls (expected not BE).
17) Why are positive and negative controls important in this program?
Because the program is not simply about detecting drug in skin. It is about showing that the method can reliably demonstrate BE when BE is truly present and also discriminate when BE is not present. Control frameworks help establish discrimination sensitivity and minimize the risk of a method that only produces signal without BE relevance.
18) What kinds of outcomes is the FDA implicitly driving toward?
The implied deliverable is a non-invasive cutaneous PK methodology that can generate time-course profiles from which meaningful PK endpoints could be derived and used for BE comparisons. The FDA is looking for proof-of-principle data demonstrating both discrimination sensitivity and reproducibility.
19) What does "discrimination sensitivity" mean here?
It refers to the ability of the method to detect real differences between products when differences exist. In BE terms, a useful method should not only confirm similarity when products are truly equivalent, but also recognize non-equivalence when products differ.
20) What does "reproducibility" mean for these non-invasive methods?
Reproducibility includes getting consistent results across repeats, subjects, sites, and time. Since BE assessments require confidence that findings are not artifacts of measurement variability, reproducibility is a central evaluation criterion.
21) Does the FDA encourage cross-validation across different research groups or technologies?
Yes. The opportunity notes that FDA collaborators may ask independent teams to align key study parameters (for example, products, dose amount, dose duration) so results from different non-invasive techniques can be compared or corroborated.
22) Is the goal to replace clinical endpoint studies for topical bioequivalence?
The opportunity is designed to move the field toward a regulatory-usable in vivo approach that could reduce reliance on expensive and variable clinical endpoint trials. The program framing highlights that current gaps slow generic development and keep clinical endpoint studies in play for many products.
23) Who is offering this funding opportunity, and what is the mechanism?
It is offered by the Department of Health and Human Services (HHS), Food and Drug Administration (FDA), using a cooperative agreement funding instrument (U01). The specific opportunity identifier provided is RFA-FD-18-012.
24) What funding level and number of awards were anticipated?
The program listed an award ceiling of $250,000 and anticipated making two awards.
25) Who is eligible to apply based on the information provided?
Eligibility is broad and includes government entities, tribal organizations, public and private higher education institutions, nonprofits (with and without 501(c)(3) status), and for-profit organizations (including small businesses). This breadth reflects an intent to attract academic labs, technology developers, and applied research groups.
26) Are applicants expected to work with commercially available topical products?
Yes. The end state emphasized by the FDA is a technique usable with marketed, commercially formulated topical products in human subjects, without invasive sampling and without modifying the drug.
27) Is this opportunity still open?
The information provided states the original closing date was June 4, 2018. Based on that, it is not presented as currently open in the provided description, though the scientific framing is described as a snapshot of FDA priorities and hurdles.
28) What should a successful proof-of-principle demonstrate?
Proof-of-principle should demonstrate that the method can generate BE-relevant cutaneous PK profiles, has discrimination sensitivity (detects true differences), and is reproducible. It should also address practical issues like signal separation from skin background, calibration strategies, depth considerations, and realistic study design constraints.
Browse more opportunities from the same category: Agriculture, Consumer Protection, Food and Nutrition
Next opportunity: Announcement for Program Funding for NRCS’ Conservation Innovation Grants (CIG) for Federal fiscal year (FY) 2018 – Caribbean Area
Previous opportunity: SIKES ACT PROGRAM SUPPORT AFCEC, MULTIPLE INSTALLATIONS
Applicant Portal:
Are you interested in learning about about how to apply for this government funding opportunity? You can create a free applicant account and receive instant access to our applicant portal that many business owners like you have benefited from.
Apply for RFA FD 18 012
Applicants also applied for:
Applicants who have applied for this opportunity (RFA FD 18 012) also looked into and applied for these:
| Funding Opportunity |
|---|
| Renewal Applications: Centers of Excellence in Regulatory Science and Innovation (U01) Apply for RFA FD 18 011 Funding Number: RFA FD 18 011 Agency: Department of Health and Human Services, Food and Drug Administration Category: Agriculture, Consumer Protection, Food and Nutrition Funding Amount: $5,000,000 |
| Assuring Radiation Protection (U18) Apply for RFA FD 18 021 Funding Number: RFA FD 18 021 Agency: Department of Health and Human Services, Food and Drug Administration Category: Agriculture, Consumer Protection, Food and Nutrition Funding Amount: $400,000 |
| Exploration of HL7 FHIR Standards for Clinical Research and Post-market Surveillance (U24) Apply for RFA FD 18 016 Funding Number: RFA FD 18 016 Agency: Department of Health and Human Services, Food and Drug Administration Category: Agriculture, Consumer Protection, Food and Nutrition Funding Amount: $250,000 |
| Development of a virtual bioequivalence trial simulation platform that integrates population pharmacokinetic modeling algorithms into physiologically-based pharmacokinetic models (U01) Apply for RFD FD 18 018 Funding Number: RFD FD 18 018 Agency: Department of Health and Human Services, Food and Drug Administration Category: Agriculture, Consumer Protection, Food and Nutrition Funding Amount: $1,800,000 |
| Cooperative Agreement to Support the Food and Agriculture Organization (FAO) (U01) Apply for RFA FD 18 009 Funding Number: RFA FD 18 009 Agency: Department of Health and Human Services, Food and Drug Administration Category: Agriculture, Consumer Protection, Food and Nutrition Funding Amount: $1,000,000 |
| Cooperative Agreement to Support Regulatory Research Related to the 2018 Prescription Drug User Fee Act and the 21st Century Cures Act Apply for RFA FD 18 013 Funding Number: RFA FD 18 013 Agency: Department of Health and Human Services, Food and Drug Administration Category: Agriculture, Consumer Protection, Food and Nutrition Funding Amount: $4,200,000 |
| Strengthen Regulatory Systems to Ensure the Safety and Quality of Food and Medical Products (U01) Apply for RFA FD 18 022 Funding Number: RFA FD 18 022 Agency: Department of Health and Human Services, Food and Drug Administration Category: Agriculture, Consumer Protection, Food and Nutrition Funding Amount: $4,500,000 |
| Cooperative Agreement to Support Regulatory Research Related to the 2018 Prescription Drug User Fee Act and the 21st Century Cures Act (U19) Apply for RFA FD 18 025 Funding Number: RFA FD 18 025 Agency: Department of Health and Human Services, Food and Drug Administration Category: Agriculture, Consumer Protection, Food and Nutrition Funding Amount: $4,000,000 |
| Development of a virtual bioequivalence trial simulation platform that integrates population pharmacokinetic modeling algorithms into physiologically-based pharmacokinetic models (U01) Apply for RFA FD 18 018 Funding Number: RFA FD 18 018 Agency: Department of Health and Human Services, Food and Drug Administration Category: Agriculture, Consumer Protection, Food and Nutrition Funding Amount: $1,800,000 |
| Strengthening Global Competency and Capacity in Inspectional Approaches and Good Manufacturing Practices (GMP) (U01) Apply for RFA FD 18 024 Funding Number: RFA FD 18 024 Agency: Department of Health and Human Services, Food and Drug Administration Category: Agriculture, Consumer Protection, Food and Nutrition Funding Amount: $1,500,000 |
| Minor Use Minor Species Development of Drugs (R01) Apply for PAR 18 827 Funding Number: PAR 18 827 Agency: Department of Health and Human Services, Food and Drug Administration Category: Agriculture, Consumer Protection, Food and Nutrition Funding Amount: $150,000 |
| Request for Information (RFI): FDA Standard Core Clinical Outcome Assessments and Endpoints Apply for RFI NOT FD 18 014 Funding Number: RFI NOT FD 18 014 Agency: Department of Health and Human Services, Food and Drug Administration Category: Agriculture, Consumer Protection, Food and Nutrition Funding Amount: $1,000,000 |
| Validating Human Stem Cell Cardiomyocyte Technology for Better Predictive Assessment of Drug-Induced Cardiac Toxicity (U01 Clinical Trial Not Allowed) Apply for RFA FD 19 002 Funding Number: RFA FD 19 002 Agency: Department of Health and Human Services, Food and Drug Administration Category: Agriculture, Consumer Protection, Food and Nutrition Funding Amount: $1,500,000 |
| Patient Reported Outcomes Tool Development for Use in Non-Cystic Fibrosis Bronchiectasis Clinical Trials (U01) Clinical Trial Optional Apply for RFA FD 19 005 Funding Number: RFA FD 19 005 Agency: Department of Health and Human Services, Food and Drug Administration Category: Agriculture, Consumer Protection, Food and Nutrition Funding Amount: $2,000,000 |
| Patient Reported Outcomes Tool Development for Use in Non-Cystic Fibrosis Bronchiectasis Clinical Trials (U01- Clinical Trial Required) Activity Code Apply for RFA FD 19 014 Funding Number: RFA FD 19 014 Agency: Department of Health and Human Services, Food and Drug Administration Category: Agriculture, Consumer Protection, Food and Nutrition Funding Amount: $2,000,000 |
| Bioequivalence of Topical Products: Bioequivalence Considerations for Ungual, Scalp, Vaginal, Anal or Rectal Dosage Forms (U01 Clinical Trial Not Allowed) Apply for RFA FD 19 008 Funding Number: RFA FD 19 008 Agency: Department of Health and Human Services, Food and Drug Administration Category: Agriculture, Consumer Protection, Food and Nutrition Funding Amount: $500,000 |
| Bioequivalence of Topical Products: Elucidating the Sensorial and Functional Characteristics of Compositionally Different Topical Formulations (U01 Clinical Trial Required) Apply for RFA FD 19 009 Funding Number: RFA FD 19 009 Agency: Department of Health and Human Services, Food and Drug Administration Category: Agriculture, Consumer Protection, Food and Nutrition Funding Amount: $1,000,000 |
| Bioequivalence of Topical Products: Evaluating the Cutaneous Pharmacokinetics of Topical Drug Products Using Pharmacokinetic Tomography (U01 Clinical Trial Not Allowed) Apply for RFA FD 19 010 Funding Number: RFA FD 19 010 Agency: Department of Health and Human Services, Food and Drug Administration Category: Agriculture, Consumer Protection, Food and Nutrition Funding Amount: $1,500,000 |
| Cooperative Agreement to Support the Illinois Institute of Technology's Institute for Food Safety and Health (U19 Clinical Trial Optional) Apply for RFA FD 19 003 Funding Number: RFA FD 19 003 Agency: Department of Health and Human Services, Food and Drug Administration Category: Agriculture, Consumer Protection, Food and Nutrition Funding Amount: $10,000,000 |
| Enhancing Regulatory Science for the Risk Based Quality Assessment of Complex Products (U01) - Clinical Trials Optional Apply for RFA FD 19 011 Funding Number: RFA FD 19 011 Agency: Department of Health and Human Services, Food and Drug Administration Category: Agriculture, Consumer Protection, Food and Nutrition Funding Amount: $3,000,000 |
Grant application guides and resources
It is always free to apply for government grants. However the process may be very complex depending on the funding opportunity you are applying for. Let us help you!
Apply for Grants
Inside Our Applicants Portal
Access Applicants Portal
- Grants Repository - Access current and historic funding opportunities with ease. Thousands of funding opportunities are published every week. We can help you sort through the database and find the eligible ones to apply for.
- Applicant Video Guides - The grant application process can be challenging to follow. We can help you with intuitive video guides to speed up the process and eliminate errors in submissions.
- Grant Proposal Wizard - We have developed a network of private funding organizations and investors across the United States. We can reach out and submit your proposal to these contacts to maximize your chances of getting the funding you need.
Premium leads for funding administrators, grant writers, and loan issuers
Thousands of people visit our website for their funding needs every day. When a user creates a grant proposal and files for submission, we pass the information on to funding administrators, grant writers, and government loan issuers.
If you manage government grant programs, provide grant writing services, or issue personal or government loans, we can help you reach your audience.
Learn More
Request more information:
Would you like to learn more about this funding opportunity, similar opportunities to "RFA FD 18 012", eligibility, application service, and/or application tips? Submit an inquiry below:
Don't forget to subscribe to our grant alerts mailing list to receive weekly alerts on new and updated grant funding opportunities like this one in your email.