Opportunity Information: Apply for RFA FD 13 013
Apply for RFA FD 13 013
- The Food Drug Administration in the health science and technology and other research and development sector is offering a public funding opportunity titled "Systematic Evaluation of Excipient Effects on the Efficacy of Metered Dose Inhaler Products (U01)" and is now available to receive applicants.
- Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.103 Food and Drug AdministrationResearch.
- This funding opportunity was created on May 7, 2013 and posted on May 7, 2013.
- Applicants must submit their applications by Jul 1, 2013. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
- The funding agency has allocated a total of $500,000.00 to eligible and selected applicants.
- Each selected applicant is eligible to receive up to $500,000.00 in funding.
- The number of recipients for this funding is limited to 7 candidate(s).
- Eligible applicants include: State governments Public and State controlled institutions of higher education Public housing authorities/Indian housing authorities Small businesses City or township governments Special district governments Nonprofits having a 501(c)(3) status with the IRS, other than institutions of higher education Others (see text field entitled Additional Information on Eligibility for clarification) County governments Native American tribal governments (Federally recognized) For profit organizations other than small businesses Private institutions of higher education Native American tribal organizations (other than Federally recognized tribal governments) Nonprofits that do not have a 501(c)(3) status with the IRS, other than institutions of higher education.
- Eligible Agencies of the Federal Government U.S. Territory or Possession Native American Tribal Organizations (other than Federally recognized tribal governments) Faith based or Community based Organization Regional Organizations Non domestic (non U.S.) Entities (Foreign Institutions)
[Watch] Creating a grant proposal using the step-by-step wizard inside the applicant portal:
Opportunity Summary:
The FDA grant opportunity "Systematic Evaluation of Excipient Effects on the Efficacy of Metered Dose Inhaler Products (U01)" is focused on a practical problem in metered dose inhaler (MDI) development: formulators know from experience that excipients can strongly influence how an MDI performs, but the field lacks a consistent, systematic, and broadly applicable understanding of how specific excipient levels translate into measurable changes in product performance. In particular, the FDA is calling out uncertainty around how much MDI aerosolization and related performance attributes depend on the concentrations of commonly used co-solvents and surfactants in hydrofluoroalkane (HFA)-based MDIs. By generating a structured evidence base, the project is intended to fill a scientific gap and also strengthen the FDA's ability to review MDI submissions under a Quality by Design (QbD) framework, where understanding formulation design space and sources of variability is central.
The core objective is to investigate how excipient concentrations affect aerosolization performance in typical HFA-based MDI formulations and to determine how sensitive available in vitro testing methods are at detecting those excipient-driven changes. In other words, the work is not just about seeing whether performance changes, but also about whether the standard and emerging lab tests used for MDIs are capable of reliably picking up those changes and distinguishing meaningful effects from noise. This matters directly to product development, post-approval changes, and equivalence assessments because relatively small formulation adjustments (even within typical acceptance limits) may or may not alter delivered dose behavior, particle size distribution, or predicted lung deposition.
The program lays out a four-phase study plan. Phase 1 is about setting up a study design that produces results that generalize beyond a single drug product. Applicants are expected to select drug candidates based on physicochemical properties so the findings can inform other compounds, not just the specific test articles. The candidates must represent both solution MDIs and suspension MDIs, because the role excipients play can differ significantly between dissolved and dispersed drug systems. For the suspension MDI candidates, the announcement specifically calls for processing (micronization) to generate two distinct particle size distributions that bracket the range seen in marketed products. That approach is meant to test whether excipient effects interact with particle size, which is a known driver of suspension stability and aerosol performance.
Phase 2 is the main experimental block and centers on three excipients that are especially relevant to HFA MDIs: ethanol as a co-solvent, oleic acid as a surfactant, and HFA 134a as the propellant. The grant expects a systematic exploration of how varying levels of these three ingredients influence MDI performance. To keep the work feasible without sacrificing statistical rigor, applicants are encouraged to use formal design-of-experiments approaches such as full or fractional factorial designs, central composite designs, or Box-Behnken designs. Excipient levels should be chosen with reference to the FDA Inactive Ingredient Database (IID) safety limits, and the study must cover scenarios where excipient amounts change both within and outside the FDA's recommended Q2 acceptance limit of 5 (as described in the announcement). Performance testing is expected to include both compendial methods (using USP and/or FDA Guidance for Industry approaches) and non-compendial methods. The non-compendial testing examples explicitly include dissolution testing and predictive total lung deposition using physical airway models, signaling an interest in linking formulation changes to more mechanistic or clinically relevant performance predictors rather than relying only on standard dose-content metrics.
Phase 3 extends the learning from Phase 2 to other surfactants beyond oleic acid. The announcement names povidone, lecithin NF, and sorbitan trioleate as examples. Each surfactant is to be evaluated at multiple levels, with level selection guided by each ingredient's IID safety limit and relevant literature. The intent here is to determine whether the patterns observed with oleic acid represent broader surfactant behavior in HFA MDI systems or whether different surfactants introduce distinct performance sensitivities, which would be important for formulation flexibility and for assessing changes during lifecycle management.
Phase 4 is intended to turn the experimental findings into usable predictive tools and regulatory-relevant guidance. Applicants are expected to develop mathematical model(s) that can predict how changes in excipient amounts affect in vitro MDI performance. The emphasis on modeling suggests the FDA is looking for outputs that support QbD-style design space definition, risk assessment, and potentially more science-based justifications for formulation or manufacturing changes. The end product is expected to include overall recommendations informed by the data and models, which could help standardize how excipient variability is evaluated during development and review.
Administratively, this opportunity is a discretionary cooperative agreement (U01) from the FDA (CFDA 93.103), meaning awardees should expect substantial FDA scientific involvement and collaboration rather than a fully investigator-driven grant structure. The posting date was May 7, 2013, with an original and final closing date of July 1, 2013, and an archive date of July 31, 2013. The expected number of awards was 7, and the funding details listed an estimated total funding amount of $500,000 with an award ceiling and floor both stated as $500,000 (as provided in the source text). Cost sharing was not required. Eligibility was broad, spanning state and local governments, public and private institutions of higher education, nonprofits with and without 501(c)(3) status, small businesses and other for-profit entities, tribal governments and organizations, U.S. territories or possessions, faith-based and community-based organizations, regional organizations, and even non-U.S. entities (foreign institutions), along with eligible federal agencies. The announcement also provided a grants management contact at the FDA for access issues.
Overall, the opportunity is essentially a targeted research push to quantify and model how MDI excipient levels shape aerosolization and related in vitro performance, using statistically planned experiments, a mix of standard and advanced testing methods, and culminating in predictive models that can support QbD-driven regulatory review and more robust product development decisions.
FAQs: Systematic Evaluation of Excipient Effects on the Efficacy of Metered Dose Inhaler Products (U01)
What is the main purpose of this FDA grant opportunity?
The opportunity supports research to build a systematic, broadly applicable understanding of how excipient concentrations change the aerosolization performance of hydrofluoroalkane (HFA)-based metered dose inhalers (MDIs). A key goal is to reduce current uncertainty about how common co-solvents and surfactants influence measurable product performance and to strengthen FDA review under a Quality by Design (QbD) framework.
What specific problem is the FDA trying to address?
MDI formulators often know from experience that excipients can significantly affect performance, but the field lacks a consistent evidence base that links specific excipient levels to specific performance changes in a way that generalizes across products. The FDA is particularly calling out uncertainty around the degree to which MDI aerosolization and related attributes depend on concentrations of commonly used co-solvents and surfactants in HFA MDIs.
What does the FDA mean by evaluating both excipient effects and test sensitivity?
The project is expected to determine (1) whether changing excipient levels measurably changes MDI performance, and (2) whether available in vitro testing methods (standard and emerging) are sensitive and reliable enough to detect those excipient-driven changes and distinguish real effects from experimental noise.
Why is this research considered important for Quality by Design (QbD)?
QbD relies on understanding formulation design space and sources of variability. By quantifying how excipient variability affects in vitro performance and turning the results into predictive models, the project can support science-based design space definition, risk assessment, and regulatory justifications for formulation or manufacturing changes.
What kinds of MDI formulations must be included?
The study is expected to include both solution MDIs and suspension MDIs. The announcement highlights that excipients can play different roles depending on whether the drug is dissolved (solution) or dispersed (suspension), so both systems are required to make findings more broadly applicable.
How should drug candidates be selected in Phase 1?
Applicants are expected to select drug candidates based on physicochemical properties so the outcomes can generalize beyond a single drug product. The intent is that the findings inform other compounds, not only the specific test articles used in the study.
What additional requirement applies to suspension MDI candidates?
For suspension MDIs, the announcement specifies processing (micronization) to create two distinct particle size distributions that bracket the range seen in marketed products. This is meant to test whether excipient effects interact with particle size, which can influence suspension stability and aerosol performance.
What are the four phases of work described in the program?
The program outlines a four-phase plan: Phase 1 focuses on designing a study that generalizes across products and includes both solution and suspension MDIs; Phase 2 conducts the primary experiments varying key excipients and measuring performance with multiple test methods; Phase 3 expands evaluation to additional surfactants beyond oleic acid; Phase 4 develops mathematical models and overall recommendations based on the data.
Which excipients are the main focus of Phase 2?
Phase 2 centers on three excipients relevant to HFA MDIs: ethanol (a co-solvent), oleic acid (a surfactant), and HFA 134a (the propellant). The work is expected to systematically explore how changing levels of these ingredients influences MDI performance.
How does the opportunity suggest designing the experiments in Phase 2?
To balance feasibility with statistical rigor, applicants are encouraged to use formal design-of-experiments approaches such as full or fractional factorial designs, central composite designs, or Box-Behnken designs when exploring excipient levels and their effects.
How should excipient level ranges be chosen?
Excipient levels should be chosen with reference to FDA Inactive Ingredient Database (IID) safety limits. The study is also expected to cover scenarios where excipient amounts change both within and outside the FDA recommended Q2 acceptance limit of 5, as described in the announcement.
What is meant by the Q2 acceptance limit of 5 in this announcement?
The opportunity specifies that the study must include excipient changes that fall within and outside the FDA recommended Q2 acceptance limit of 5 (as stated in the announcement). This requirement is included to test whether relatively small formulation adjustments, as well as larger ones, produce detectable performance differences.
What types of performance testing are expected?
Performance testing is expected to include both compendial methods (using USP and/or FDA Guidance for Industry approaches) and non-compendial methods. The announcement explicitly includes examples of non-compendial testing such as dissolution testing and predictive total lung deposition using physical airway models.
Why does the announcement emphasize non-compendial methods like dissolution and airway models?
By including dissolution testing and predictive total lung deposition using physical airway models, the FDA signals interest in approaches that may link formulation changes to more mechanistic or clinically relevant predictors, rather than relying only on standard dose or content metrics.
What is the purpose of Phase 3?
Phase 3 extends the work beyond oleic acid to other surfactants to see whether the trends observed with oleic acid reflect broader surfactant behavior in HFA MDI systems or whether different surfactants create distinct performance sensitivities.
Which additional surfactants are mentioned as examples for Phase 3?
The announcement lists povidone, lecithin NF, and sorbitan trioleate as examples of surfactants to evaluate beyond oleic acid.
How should surfactant levels be selected in Phase 3?
Each surfactant is to be evaluated at multiple levels, with selection guided by the ingredient's IID safety limit and relevant literature, according to the announcement.
What is expected as the main output of Phase 4?
Phase 4 is intended to produce mathematical model(s) that predict how changes in excipient amounts affect in vitro MDI performance, along with overall recommendations informed by the experimental data and models.
How are the outputs intended to be used by the FDA and industry?
The outputs are positioned to support QbD-style development and review by helping define formulation design space, understand sources of variability, and provide more science-based support for post-approval changes and equivalence assessments where small formulation adjustments may or may not change delivered dose behavior or particle size-related performance.
What award mechanism is used for this funding opportunity?
The mechanism is a discretionary cooperative agreement (U01). This indicates substantial FDA scientific involvement and collaboration, rather than a fully investigator-driven structure.
What is the CFDA number listed for this opportunity?
The CFDA number provided is 93.103.
How many awards were expected?
The opportunity listed an expected number of awards of 7.
What funding amount and award limits are stated in the posting?
The posting lists an estimated total funding amount of $500,000, with both the award ceiling and award floor stated as $500,000 (as provided in the source text).
Is cost sharing required?
No. The opportunity states that cost sharing is not required.
Who is eligible to apply based on the opportunity description?
Eligibility is broad and includes state and local governments; public and private institutions of higher education; nonprofits with and without 501(c)(3) status; small businesses and other for-profit entities; tribal governments and organizations; U.S. territories or possessions; faith-based and community-based organizations; regional organizations; non-U.S. entities (foreign institutions); and eligible federal agencies.
Does the opportunity allow foreign (non-U.S.) institutions to apply?
Yes. The eligibility list explicitly includes non-U.S. entities (foreign institutions).
What were the key dates for this opportunity?
The posting date was May 7, 2013. The original closing date and final closing date were both July 1, 2013. The archive date was July 31, 2013.
What kind of involvement should awardees expect from the FDA?
Because this is a cooperative agreement (U01), awardees should expect substantial FDA scientific involvement and collaboration during the project, as opposed to a fully independent, investigator-driven grant.
What does the opportunity suggest about handling access issues?
The announcement notes that a grants management contact at the FDA was provided for access issues.
What broader development and regulatory questions does this study aim to inform?
The work is intended to help address questions relevant to product development, post-approval changes, and equivalence assessments, especially where changes in excipient levels (even within typical acceptance limits) may affect delivered dose behavior, particle size distribution, or predicted lung deposition.
Browse more opportunities from the same category: Health Science and Technology and other Research and Development
Next opportunity: Programmatic Accessibility Evaluations Rocky Mountain NP
Previous opportunity: Development of in vivo predictive dissolution method for orally inhaled drug products
USGrants.org 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 13 013
[Watch] how do funding administrators access proposals?
Applicants also applied for:
Applicants who have applied for this opportunity (RFA FD 13 013) also looked into and applied for these:
| Funding Opportunity |
|---|
| Pharmacometric Modeling and Simulation for Generic Drugs Evaluation Apply for RFA FD 14 011 Funding Number: RFA FD 14 011 Agency: Food Drug Administration Category: Health Science and Technology and other Research and Development Funding Amount: $250,000 |
| Characterization of Critical Quality Attributes for Semisolid Topical Drug Products Apply for RFA FD 14 010 Funding Number: RFA FD 14 010 Agency: Food Drug Administration Category: Health Science and Technology and other Research and Development Funding Amount: $250,000 |
| Dissolution Methods for Semisolid Ocular Drug Products Apply for RFA FD 14 008 Funding Number: RFA FD 14 008 Agency: Food Drug Administration Category: Health Science and Technology and other Research and Development Funding Amount: $350,000 |
| Dissolution Methods for Microsphere and Implant Drug Products Apply for RFA FD14 007 Funding Number: RFA FD14 007 Agency: Food Drug Administration Category: Health Science and Technology and other Research and Development Funding Amount: $500,000 |
| Dissolution Methods for Suspension and Emulsion Ocular Drug Products Apply for RFA FD 14 009 Funding Number: RFA FD 14 009 Agency: Food Drug Administration Category: Health Science and Technology and other Research and Development Funding Amount: $250,000 |
| Evaluation of in vitro release methods for liposomal drug products Apply for RFA FD 14 016 Funding Number: RFA FD 14 016 Agency: Food Drug Administration Category: Health Science and Technology and other Research and Development Funding Amount: $500,000 |
| Development of realistic in vitro studies to assess robustness of dose counters/indicators in metered dose inhalers (U01) Apply for RFA FD 14 025 Funding Number: RFA FD 14 025 Agency: Food Drug Administration Category: Health Science and Technology and other Research and Development Funding Amount: $500,000 |
| Evalution of Iron Species in Healthy Subjects treated with Generic and Reference Sodium Ferric Gluconate Apply for RFA FD 14 019 Funding Number: RFA FD 14 019 Agency: Food Drug Administration Category: Health Science and Technology and other Research and Development Funding Amount: $500,000 |
| Retrospective Analysis on the Impact of Generic Immunosuppressants on Acute Rejection and Long Term Graft Survivals (U01) Apply for RFA FD 14 021 Funding Number: RFA FD 14 021 Agency: Food Drug Administration Category: Health Science and Technology and other Research and Development Funding Amount: $1,000,000 |
| Pharmacokinetic and Pharmacodynamic (PK PD) Studies of Cardiovascular Drugs (U01) Apply for RFA FD 14 024 Funding Number: RFA FD 14 024 Agency: Food Drug Administration Category: Health Science and Technology and other Research and Development Funding Amount: $1,000,000 |
| Prospective Studies on the Impact of Generic Immunosuppressants on Acute Rejection and Long Term Graft survivals (U01) Apply for RFA FD 14 020 Funding Number: RFA FD 14 020 Agency: Food Drug Administration Category: Health Science and Technology and other Research and Development Funding Amount: $1,000,000 |
| Post market surveillance evaluation of authorized generic drug products (U01) Apply for RFA FD 14 013 Funding Number: RFA FD 14 013 Agency: Food Drug Administration Category: Health Science and Technology and other Research and Development Funding Amount: $400,000 |
| Effect of Therapeutic Class on Generic Drug Substitutions (U01) Apply for RFA FD 14 014 Funding Number: RFA FD 14 014 Agency: Food Drug Administration Category: Health Science and Technology and other Research and Development Funding Amount: $400,000 |
| Pharmacokinetic/Pharmacodynamic (PK/PD) Studies of Methylphenidate Extended Release Products in Attention Deficit Hyperactivity Disorder (ADHD) Patients (U01) Apply for RFA FD 14 015 Funding Number: RFA FD 14 015 Agency: Food Drug Administration Category: Health Science and Technology and other Research and Development Funding Amount: $1,000,000 |
| Community Health Peer Learning Program Apply for CLP CL 15 001 Funding Number: CLP CL 15 001 Agency: Office of the National Coordinator Category: Health Science and Technology and other Research and Development Funding Amount: $1,700,000 |
| Suicide Prevention and Counseling Research Apply for W81XWH 08 MOMRP SPCR Funding Number: W81XWH 08 MOMRP SPCR Agency: Dept. of the Army USAMRAA Category: Health Science and Technology and other Research and Development Funding Amount: $2,000,000 |
| Molybdenum 99 Apply for DE FOA 0000323 Funding Number: DE FOA 0000323 Agency: NNSA Category: Health Science and Technology and other Research and Development Funding Amount: Case Dependent |
| Advancing Regulatory Science through Novel Biomarker Research and Science Based Technologies Apply for RFA FD 11 016 Funding Number: RFA FD 11 016 Agency: Food Drug Administration Category: Health Science and Technology and other Research and Development Funding Amount: $350,000 |
| Advancing Regulatory Science Through Development of Innovative Methodologies in the area of Antimicrobial Development (U01) Apply for RFA FD 11 026 Funding Number: RFA FD 11 026 Agency: Food Drug Administration Category: Health Science and Technology and other Research and Development Funding Amount: $100,000 |
| The Effect of Different Preparation Methods on the In Vitro and In Vivo Performance of Solid Dispersion Formulations (U01) Apply for RFA FD 14 023 Funding Number: RFA FD 14 023 Agency: Food Drug Administration Category: Health Science and Technology and other Research and Development Funding Amount: $500,000 |
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
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.
Subscribe to Leads
Request more information:
Would you like to learn more about this funding opportunity, similar opportunities to "RFA FD 13 013", 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.