CFD Models to aid the development of generic inhalation products | FOR FD 20 023

Opportunity Information: Apply for FOR FD 20 023

This FDA grant opportunity (Funding Opportunity Number FOR FD 20 023; CFDA 93.103) supports research that uses computational fluid dynamics (CFD) modeling to improve the development of generic orally inhaled drug products, specifically metered dose inhalers (MDIs) and dry powder inhalers (DPIs). The core issue the program is trying to solve is that FDA product-specific guidance for demonstrating bioequivalence in these products typically relies on a weight-of-evidence package. That package commonly includes in vitro performance testing, an in vivo pharmacokinetic (PK) study, and then either an in vivo pharmacodynamic (PD) study or a comparative clinical endpoint (CCEP) study. While this approach is workable, it can be difficult and expensive for generic developers because it is not always clear how the standard in vitro metrics connect to what ultimately matters clinically: the rate and extent of drug delivered to the intended regions of the lung.

The main goal of the funded work is to generate CFD-based predictions of regional lung deposition for at least one currently marketed MDI or DPI, covering both upper and lower human airways. In other words, applicants are expected to build models that can simulate how aerosol particles travel through realistic airway geometries and where they deposit, and then to show that these predictions are trustworthy. The solicitation emphasizes verification and validation: the models should not just be built, but also checked for numerical correctness (verification) and demonstrated to match reality (validation) using either in vitro data (for example, data from established aerosol characterization or airway replica testing) or in vivo data where available. The expectation is that the resulting models will be credible enough to inform regulatory-relevant questions about inhaler performance and equivalence.

Once a model has been verified and validated, the project is expected to go further by running a parameter sensitivity analysis. The intent of this phase is to test how changes in key inputs and device/formulation attributes influence predicted regional deposition, and then to use those results to evaluate how biopredictive common in vitro tests really are. Practically, this means identifying which in vitro metrics (such as aerodynamic particle size distribution, or APSD, and other performance measurements) most strongly track with deposition in specific lung regions, and where in vitro tests may be insensitive or misleading. Over time, this kind of mapping can help clarify which laboratory measurements best predict in vivo delivery, potentially reducing uncertainty for generic developers and helping align test strategies with clinical relevance.

The announcement also highlights technology options tailored to each inhaler type. For DPIs, FDA notes that discrete element modeling (DEM) may be incorporated to better represent particle-particle interactions, particularly agglomeration and deagglomeration processes in carrier and active pharmaceutical ingredient blends. Since DPI performance is heavily influenced by how powders break apart and disperse during inhalation, coupling DEM with CFD can improve predictions of how these micro-scale powder behaviors translate into aerosol formation, APSD outcomes, and ultimately regional deposition. For MDIs, the opportunity signals a preference for studying formulations with at least three components, reflecting the reality that many modern MDI systems involve multiple formulation constituents (for example, propellant plus co-solvent and other excipients), which can affect spray formation, droplet evaporation, plume dynamics, and deposition.

Administratively, the program is run by the Department of Health and Human Services (HHS), Food and Drug Administration (FDA), and is offered as a discretionary grant. Eligibility is broad and includes state and local governments, tribal governments and organizations, public and private institutions of higher education, nonprofits (with or without 501(c)(3) status), for-profit organizations (excluding small businesses in one category but separately including small businesses as eligible), and certain housing authorities. The opportunity posting indicates an expected number of awards of two, and lists an award ceiling of 0, which typically means the ceiling was not specified in the excerpted listing rather than indicating no funding. The posting date is May 25, 2021, and the original closing date is shown as an archiving forecast, suggesting the listing may have been moved into an archived status or the date was not populated in the extracted record.

Overall, the grant is aimed at strengthening the scientific bridge between in vitro inhaler performance tests and real-world lung delivery by producing rigorously validated CFD (and potentially CFD-DEM) tools. If successful, the work could make it easier to design and evaluate generic MDIs and DPIs by clarifying which in vitro measurements are most predictive of regional deposition, and by providing modeling approaches that can support more efficient, evidence-based bioequivalence strategies.

• The Department of Health and Human Services, Food and Drug Administration in the consumer protection, food and nutrition, health sector is offering a public funding opportunity titled "CFD Models to aid the development of generic inhalation products" 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 May 25, 2021.
• Applicants must submit their applications by Archiving forecast. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• 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.

Apply for FOR FD 20 023

[Watch] Creating a grant proposal using the step-by-step wizard inside the applicant portal: