Developing PBPK Model-Based Mechanistic IVIVCs for Long Acting Injectable Suspensions and Implants (U01) Clinical Trial Optional

Status
Forecasted
Total Funding
$600,000.00
Award Ceiling
$300,000.00
Expected No. Awards
2
Opportunity No.
FOR-FD-24-002

Agency

Food and Drug Administration (HHS-FDA)

Eligible Applicants

Others

Funding Category

Health

Funding Instrument

Cooperative Agreement

Opportunity Category

Discretionary

Cost Sharing or Matching Requirement

Yes

Summary

The Food and Drug Administration (FDA) is offering a federal grant opportunity titled "Developing PBPK Model-Based Mechanistic IVIVCs for Long Acting Injectable Suspensions and Implants (U01) Clinical Trial Optional". This grant aims to develop physiologically based pharmacokinetic (PBPK) model-based mechanistic in vitro in vivo correlations (IVIVCs) for long-acting injectables (LAIs) such as crystalline suspensions and polymer-based implants. The objective of this research proposal is to create a bottom-up mechanistic PBPK model for these two categories of LAIs by considering their distinct characteristics and the influence of critical formulation attributes. The goal is to predict the in vivo release mechanism of each LAI drug product type by incorporating relevant physiology and suitable in vitro and in vivo experiments. The PBPK model can be validated using a suitable preclinical animal model. This research will provide insights into how the physicochemical properties of drug molecules/polymer, implant-specific properties, critical formulation attributes, and physiology influence the in vivo release mechanisms and disposition characteristics of LAI drug products. The developed PBPK model will help define the "safe space" for critical formulation attributes, explain sources of pharmacokinetic variability, and extrapolate predictions to human subjects by leveraging animal model data and accounting for species-specific physiological differences. The grant has an estimated total program funding of $600,000, with an award ceiling of $300,000. It is a cooperative agreement and falls under the category of funding activity related to health. The grant is forecasted for the fiscal year 2024, and it is open to eligible applicants, including independent school districts, public housing authorities, Native American tribal organizations, and non-domestic entities. For more information, interested parties can contact Terrin Brown, a Grants Management Specialist at the FDA, via email at Terrin.Brown@fda.hhs.gov or by phone at 240-402-7610.

Description

The objective of this research proposal is to develop physiologically based pharmacokinetic (PBPK) model-based mechanistic in vitro in vivo correlations (IVIVCs) for two major types of long acting injectables (LAIs) such as crystalline suspensions and polymer-based implants by considering their distinct characteristics. The goal of the project is to develop a bottom-up mechanistic PBPK model for these two LAI categories by accounting for the influence of critical formulation attributes of each LAI drug product type to predict its in vivo release mechanism. The model formulation parameters and relevant physiology should be informed with suitable in vitro and in vivo experiments. A suitable preclinical animal model can be used to validate the PBPK model based IVIVCs for both LAI suspensions and polymer based implants. The use of PBPK modelling provides a unique opportunity to understand how the physicochemical properties of drug molecules/polymer, implant specific properties, critical formulation attributes, and physiology, among other things, influence the in vivo release mechanisms of LAI drug products and their disposition characteristics. Moreover, once developed, a mechanistic PBPK model can help to define the 'safe space' for critical formulation attributes relevant to the reference listed drug (RLD) product, explain sources of PK variability and extrapolate predictions to human subjects by leveraging animal model data and by accounting for species-specific physiological differences.

Contact Information

PrimaryTerrin Brown Grants Management Specialist
(240) 402-7610
Terrin.Brown@fda.hhs.gov

Opportunity Lifecycle

Title
Type
Grant

Similar Opportunities

Improving Predictability of Food-Drug and Drug-Drug Interaction Risks by Utilizing In Vitro Simulated Gastrointestinal Dissolution Model for High-Risk Oral Drug Products (U01) Clinical Trial Optional
Food and Drug Administration
The Food and Drug Administration (FDA) is offering a federal grant opportunity titled "Improving Predictability of Food-Drug and Drug-Drug Interaction Risks by Utilizing In Vitro Simulated Gastrointestinal Dissolution Model for High-Risk Oral Drug Products (U01) Clinical Trial Optional". This funding opportunity falls under the category of Consumer Protection and is a Cooperative Agreement type of funding instrument. The grant does not require cost sharing or matching. The purpose of this funding opportunity is to examine the utility of an in vitro simulated gastrointestinal (GI) dissolution model for the assessment of in vitro performance of amorphous solid dispersion (ASD) drug products under different clinically relevant conditions. The goal is to develop and validate the in vitro mechanistic methodology to provide an improved understanding of the impact of food and acid reducing agents on the absorption for test and reference listed drug (RLD) drug products, taking into consideration their potentially different formulations and manufacturing. The bio predictive in vitro mechanistic methodology is intended to correlate the in vitro observations to in vivo outcomes, help define types of in vivo bioequivalence (BE) studies needed for ASD drug products, and inform regulatory decision-making related to mitigating the risk of potential failure modes for therapeutic equivalence for high-risk generic oral drug products. The grant has an award ceiling of $500,000 and an award floor of $250,000. It is expected that there will be 2 awards given. The eligible applicants for this grant opportunity are unrestricted, meaning any applicant organization may submit an application. However, each application must be scientifically distinct. The FDA will not accept duplicate or highly overlapping applications under review at the same time. For more information and to apply for this grant opportunity, you can contact Terrin Brown, the Grantor, at terrin.brown@fda.hhs.gov or (240) 402-7610. The last updated date for this grant opportunity is November 30, 2023.
Evaluating the Cutaneous Pharmacokinetics of Topical Drug Products Using Pharmacokinetic Tomography (U01 Clinical Trial Required)
Food and Drug Administration
The Food and Drug Administration (FDA) is offering a federal grant opportunity titled "Evaluating the Cutaneous Pharmacokinetics of Topical Drug Products Using Pharmacokinetic Tomography (U01 Clinical Trial Required)". This grant falls under the category of Consumer Protection and is a Cooperative Agreement type of funding instrument. The grant does not require cost sharing or matching. The purpose of this funding opportunity is to support research and development in non-invasive technologies, specifically quantitative tomography-based methods, to evaluate the rate and extent to which a topically applied drug becomes available at or near a site of action within the skin in vivo. The funded work aims to develop an accurate, sensitive, and reproducible approach to measure the amount of drug present in the skin at various depths below the surface. This approach will be used to monitor the cutaneous pharmacokinetics (PK) of the drug over time. The ultimate goal is to develop a scientifically valid in vivo cutaneous PK-based approach that can efficiently demonstrate the bioequivalence (BE) of topical products. The grant has an award ceiling and floor of $250,000, and it is expected that one award will be made. The eligibility for this grant is unrestricted, meaning any applicant organization can apply. However, each application must be scientifically distinct. The FDA will not accept duplicate or highly overlapping applications under review at the same time. For more information or to apply for this grant opportunity, you can contact Terrin Brown, the grantor, at terrin.brown@fda.hhs.gov or by phone at 240-338-7494. The deadline for this grant is forecasted to be in the fiscal year 2024.
Collaborations to Enhance Drug Development and Regulatory Science
Food and Drug Administration
The Food and Drug Administration (FDA) is offering a grant opportunity titled "Collaborations to Enhance Drug Development and Regulatory Science". This grant aims to support, manage, and facilitate Public-Private Partnerships and Collaborative activities as part of the Critical Path Initiative and to support regulatory science efforts. The FDA and grantees will work together to develop innovative, collaborative projects in research, education, and outreach. These projects can help foster drug product innovation by supporting efforts to accelerate drug product development, approaches to advanced manufacturing, translation of basic science discoveries into therapeutics, and approaches to enhance the safety, efficacy, quality, and performance of drug products. The grant has an award ceiling and floor of $5,000,000 and expects to fund 6 awards. The grant is forecasted and falls under the category of funding activity for Consumer Protection. The grant is open to unrestricted eligible applicants. The deadline for application submission is in the fiscal year 2024. For more information, you can contact Terrin Brown, the grantor, at terrin.brown@fda.hhs.gov or (240) 402-7610.
Identification of Drug-related and Formulation-Related Factors that Result in Alcohol Dose Dumping of Modified Release Oral Drug Products (U01) Clinical Trial Not Allowed
Food and Drug Administration
The Food and Drug Administration (FDA) is offering a federal grant opportunity titled "Identification of Drug-related and Formulation-Related Factors that Result in Alcohol Dose Dumping of Modified Release Oral Drug Products (U01) Clinical Trial Not Allowed". This grant aims to support research in developing tools that facilitate the development of modified release (MR) generic drug products with a low potential for alcohol dose dumping (ADD). Modified release oral drug products are designed to release drugs over a prolonged period of time and are at high risk for ADD when exposed to alcohol. Accidental exposure to alcohol can result in the rapid release of large quantities of drugs, leading to severe side effects and even death. To mitigate this risk, the FDA recommends conducting an in vitro alcohol dose dumping assessment in various alcoholic dissolution media for prospective generic versions of MR oral drug products. Currently, there is a lack of global harmonization in ADD assessments. For example, the FDA recommends testing up to 40% alcoholic media, while the European Medicines Agency recommends testing up to 20% alcoholic media. This difference poses challenges for formulators designing products for multiple markets, as historical data has shown that release from MR oral products does not always follow a linear response to increasing alcohol concentrations. The purpose of this research is to develop tools that facilitate the development of MR generic drug products with a low potential for ADD. These tools will support regulatory decision making during the assessment of such products and provide evidence for the FDA to develop more specific recommendations for demonstrating a low or comparative potential of alcohol dose dumping for MR oral drug products containing high-risk drugs. The grant has a funding ceiling and floor of $250,000 and is expected to result in one award. It falls under the category of funding activity for consumer protection. The grant is forecasted for the fiscal year 2024 and does not require cost sharing or matching. The opportunity is a cooperative agreement and is open to unrestricted eligible applicants. For more information, interested parties can contact Terrin Brown, the grantor, at terrin.brown@fda.hhs.gov or (240) 402-7610.