Department of Health and Human Services
Part 1. Overview Information
Participating Organization(s)

U.S. Food and Drug Administration (FDA)

NOTE:  The policies, guidelines, terms, and conditions stated in this announcement may differ from those used by the NIH.  Where this Funding Opportunity Announcement (FOA) provides specific written guidance that may differ from the general guidance provided in the grant application form, please follow the instructions given in this FOA.

The FDA does not follow the NIH Page Limitation Guidelines or the NIH Review Criteria. Applicants are encouraged to consult with FDA Agency Contacts for additional information regarding page limits and the FDA Objective Review Process.

Components of Participating Organizations

Center for Drug Evaluation and Research (CDER)

Funding Opportunity Title

Development of a virtual bioequivalence trial simulation platform that integrates population pharmacokinetic modeling algorithms into physiologically-based pharmacokinetic models (U01)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

New

Related Notices

None

Funding Opportunity Announcement (FOA) Number

RFA-FD-18-018

Companion Funding Opportunity

None

Catalog of Federal Domestic Assistance (CFDA) Number(s)

 93.103 

Funding Opportunity Purpose

The purpose of this project is to develop and implement a virtual bioequivalence trial simulation platform that can be used to perform population-based statistical analysis in complex and computationally intensive physiologically based pharmacokinetic (PBPK) models developed to describe the absorption, distribution and elimination of active pharmaceutical ingredients formulated in complex and non-complex dosage forms administered via oral or non-oral routes. The developed virtual bioequivalence trial simulation platform will be used to generate predictions on the in vivo drug product performance, to perform bioequivalence assessments between brand name and generic drug products and to inform regulatory decisions relating to generic drug development.  

Key Dates
Posted Date

April 20, 2018

Open Date (Earliest Submission Date)

April 20, 2018

Letter of Intent Due Date(s)

May 4, 2018

Application Due Date(s)

June 20, 2018, by 11:59 PM Eastern Time.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Applicants should be aware that on-time submission means that an application is submitted error free (of both Grants.gov and eRA Commons errors) by 11:59 PM Eastern Time on the application due date. 

Late applications will not be accepted for this FOA.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

June, 2018

Advisory Council Review

Not Applicable

Earliest Start Date

September 2018

Expiration Date

June 21, 2018

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.


There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.
  4. Table of Contents

    Part 1. Overview Information
    Part 2. Full Text of the Announcement

    Section I. Funding Opportunity Description
    Section II. Award Information
    Section III. Eligibility Information
    Section IV. Application and Submission Information
    Section V. Application Review Information
    Section VI. Award Administration Information
    Section VII. Agency Contacts
    Section VIII. Other Information

    Part 2. Full Text of Announcement
    Section I. Funding Opportunity Description

    Background

    Mechanism-based physiologically based pharmacokinetic (PBPK) models have been proven to be powerful tools in the generic drug development process and bioequivalence assessment. Major advantages of PBPK modeling include the ability to integrate information from human physiology (system-related parameters), drug physicochemical properties and interaction with enzymes and other protein structures, and drug product characteristics (e.g., the formulation type) (drug product-related parameters) to generate predictions regarding the absorption, disposition, metabolism and elimination of the drug in populations following administration of drug products via oral and non-oral routes. In addition to integrating prior information on parameter distribution into these models, experimental data can be used to estimate unknown or low certainty parameters, leading to more reliable predictions based on a well characterized system.

    Acknowledging the superiority of these predictive models, optimization routines have been incorporated into a variety of software programs currently used in the development of mechanistic PBPK models. The optimization routines that currently perform better are the ones that are successful in identifying and characterizing inter- and intra-subject variability in the population. These types of variability can be attributed to sources that include, but are not limited to, anthropometric characteristics (e.g., age, body weight/mass, and sex), experimental variability observed in in vitro dissolution/drug release studies, study design which accounts for inter-trial and inter-occasion variability and subject-by-formulation interactions.

    Models such as the ones described above are valuable in the development of safe, effective and affordable generic drug products. They allow the simulation of bioequivalence trials that compare the predicted in vivo performance of the brand name with the generic drug product one. These trials would not be feasible for a variety of reasons; conducting bioequivalence studies in special populations such as pediatrics is challenging because of ethical concerns and extrapolating model outcomes from healthy volunteers to patients, the target population, is an attractive approach. Additionally, these models allow the prediction of in vivo performance for formulations of interest based on the establishment of in vitro-in vivo correlations for drug products with similar drug delivery technologies.

    However, a platform that supports and facilitates the development of the models described above and the design and simulation of virtual bioequivalence trials to inform decisions in the generic drug product development process is not available today.

    Objective:

    The purpose of this project is to develop and implement a virtual bioequivalence trial simulation platform that can be used to perform population-based statistical analysis in complex and computationally intensive physiologically based pharmacokinetic (PBPK) models developed to describe the absorption, distribution and elimination of active pharmaceutical ingredients formulated in complex and non-complex dosage forms administered via oral or non-oral routes. The developed virtual bioequivalence trial simulation platform will be used by all stakeholders engaged in generic drug development including regulatory agencies, pharmaceutical industry and academia to generate predictions on in vivo drug product performance, to perform bioequivalence assessments between brand name and generic drug products and to inform regulatory decisions relating to generic drug development.

    Detailed description:

    The purpose of the current project is the development of a potentially open-source platform that would provide the capability to conduct virtual bioequivalence trial simulations. Ideally, this user-friendly platform will provide the user with many user-defined capabilities.  

    Applicants are encouraged to discuss items that they consider integral parts of this platform in their proposals. These platform components may include, but not be limited to:

    1. Algorithm implementation for population pharmacokinetic analysis: The current project describes the marriage between PBPK modeling and population-based statistical analysis. The latter is necessary for parameter estimation when individual-level data is available. A critical aspect of this coupling is the implementation of an algorithm that would allow the performance of population-based statistical analysis. Although novelty is encouraged in regards to the algorithm, proposals could entertain approaches such as: a. Implementing the non-linear mixed effects theory, b. Maximum log-likelihood algorithms (stiff, non-stiff Ordinary Differential Equation solving methods with linearization), c. Exact maximum likelihood with Expectation-Maximization algorithms (no linearization), d. Introducing a Bayesian population PBPK approach (Markov Chain Monte Carlo), e. Nonparametric methods.

    Proposals could include, but not be limited to, methods to evaluate the robustness of the proposed algorithm in terms of bias to initial estimates, precision, accuracy, convergence rate, and computation time, in full-body PBPK models of low, intermediate, and high complexity using simulated and real (rich and sparse) datasets.

    2. PBPK model structure to meet the needs and requirements of developing a generic drug product that can be administered via an oral or non-oral route to healthy volunteers or special populations. Features of the developed models may include:

    a. capability to administer a dosage form in the gut or through any other tissue/organ (ie. skin, lung etc.) captured in the model.

    b. capability to mechanistically describe the administration of different dosage forms that could include, but not be limited to: immediate release or extended release tablets or capsules, solutions or suspensions, aerosols, creams/ointments/emulsions/transdermal delivery systems.

    c. Capability to account for and mechanistically describe the potential impact of formulation critical quality attributes on in vivo drug product performance by incorporating them into the model. These formulation characteristics could include, but not be limited to: content uniformity, particle size and particle size distribution, viscosity and rheology characterization parameters and in vitro dissolution/drug release characterization, aerodynamic and adhesion properties.

    d. Capability to extrapolate model outcomes from one population to another by modifying physiology (system-related) parameters in the PBPK model. Most of bioequivalence studies are conducted in healthy volunteers who are not the target population. Therefore, the capability of simulating a virtual bioequivalence trial is advantageous in that it can provide an insight on the in vivo drug performance in patients to whom the drug product is intended to be administered and in special populations such as the elderly or pediatrics for whom bioequivalence studies are not always feasible to conduct.

    e. Capability to simulate different study designs that include, but are not limited to: crossover, parallel, (fully) replicated study design, single and multiple (steady state) dose studies.

    3. It desirable to be able, within the platform, to validate/qualify the previously developed PBPK models by utilizing appropriate datasets retrieved from independent and accredited literature sources, by utilizing in house data if available or by designing and conducting studies that would allow the generation of the necessary experimental datasets.

    Appropriate datasets that capture the subpopulation, study design and dosage form characteristics that were incorporated in the models are expected to be utilized for model validation/qualification.

    It is desirable that the utility and performance of the platform will be demonstrated following a well-defined research plan that will be outlined in the submitted research proposal. Virtual bioequivalence studies can be simulated on the developed platform to determine whether generic drug products that have been shown to not be bioequivalent to their innovators (positive control) or whether generic drug products that have been shown not to be bioequivalent to their innovators (negative control) are deemed not bioequivalent or bioequivalent, respectively, based on model output. Multiple scenarios should be simulated to demonstrate model flexibility, sensitivity and overall predictability within the developed. Demonstrating platform performance and utility with the appropriated examples is desired.

    See Section VIII. Other Information for award authorities and regulations.

    Section II. Award Information
    Funding Instrument

    Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, FDA scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.

    Application Types Allowed

    New

    The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

    Clinical Trial?

    Not Allowed:  Only accepting applications that do not propose clinical trials

    Funds Available and Anticipated Number of Awards

    The number of awards is contingent upon FDA appropriations and the submission of a sufficient number of meritorious applications. Award(s) will provide one (1) year of support and include future recommended support for two (2) additional years contingent upon annual appropriations, availability of funding and satisfactory awardee performance.

    FDA/Center for Drug Evaluation and Research intends to fund up to $600,000, for fiscal year 2018 in support of this grant program.

    It is anticipated that up to two (2) awards will be made, not to exceed $300,000 in total costs (direct plus indirect), per year, per award.

    Award Budget

    Application budgets need to reflect the actual needs of the proposed project and should not exceed the following in total costs (direct and indirect):

    YR 01: $300,000

    YR 02: $300,000

    YR 03: $300,000

    Award Project Period

    The scope of the proposed project should determine the project period. The maximum project period is three (3) years.

    HHS grants policies as described in the HHS Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

    Section III. Eligibility Information
    1. Eligible Applicants
    Eligible Organizations

    Higher Education Institutions

    • Public/State Controlled Institutions of Higher Education
    • Private Institutions of Higher Education

    The following types of Higher Education Institutions are always encouraged to apply for FDA support as Public or Private Institutions of Higher Education:

    • Hispanic-serving Institutions
    • Historically Black Colleges and Universities (HBCUs)
    • Tribally Controlled Colleges and Universities (TCCUs)
    • Alaska Native and Native Hawaiian Serving Institutions
    • Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

    Nonprofits Other Than Institutions of Higher Education

    • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
    • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

    For-Profit Organizations

    • Small Businesses
    • For-Profit Organizations (Other than Small Businesses)

    Governments

    • State Governments
    • County Governments
    • City or Township Governments
    • Special District Governments
    • Indian/Native American Tribal Governments (Federally Recognized)
    • Indian/Native American Tribal Governments (Other than Federally Recognized)
    • Eligible Agencies of the Federal Government
    • U.S. Territory or Possession

    Other

    • Independent School Districts
    • Public Housing Authorities/Indian Housing Authorities
    • Native American Tribal Organizations (other than Federally recognized tribal governments)
    • Faith-based or Community-based Organizations
    • Regional Organizations
    • Non-domestic (non-U.S.) Entities (Foreign Institutions)
    Foreign Institutions

    Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
    Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
    Foreign components, as defined in the HHS Grants Policy Statement, are allowed.

    Required Registrations

    Applicant Organizations

    Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission.

    • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
    • System for Award Management (SAM) (formerly CCR) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
    • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. 
    • eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
    • Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

    Program Directors/Principal Investigators (PD(s)/PI(s))

    All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

    Eligible Individuals (Program Director/Principal Investigator)

    Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for FDA support.

    For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

    2. Cost Sharing

    This FOA does not require cost sharing as defined in the HHS Grants Policy Statement.

    3. Additional Information on Eligibility
    Number of Applications

    Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

    The FDA will not accept duplicate or highly overlapping applications under review at the same time.  This means that the FDA will not accept:

    • A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
    • A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
    Section IV. Application and Submission Information
    1. Requesting an Application Package

    Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

    2. Content and Form of Application Submission

    It is critical that applicants follow the instructions in the Research Instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

    For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.

    Letter of Intent

    Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows FDA staff to estimate the potential review workload and plan the review.

    By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

    • Descriptive title of proposed activity
    • Name(s), email address(es), and telephone number(s) of the PD(s)/PI(s)
    • Names of other key personnel
    • Participating institution(s)
    • Number and title of this funding opportunity

    The letter of intent should be sent to:

    Shashi Malhotra
    Food and Drug Administration/Center for Drug Evaluation and Research/Office of the Commissioner/Office of Operations/Office of Finance, Budget and Acquisitions/Office of Acquisitions and Grants Services
    Telephone: 240-402-7592
    Email: Shashi.Malhotra@fda.hhs.gov

    A technical session will be held for prospective applicants in May, 2018. The conference call information will be provided to prospective applicants that submit a letter of intent.  The technical session will provide an overview of the submission requirements and allow prospective applicants an opportunity to ask questions regarding the application process.  Participation in the technical session is optional, but strongly encouraged. 

    Page Limitations

    All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:

    For this specific FOA, the Research Strategy section is limited to 30 pages

    Instructions for Application Submission

    The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

    SF424(R&R) Cover

    All instructions in the SF424 (R&R) Application Guide must be followed.  

    SF424(R&R) Project/Performance Site Locations

    All instructions in the SF424 (R&R) Application Guide must be followed.  

    SF424(R&R) Other Project Information

    All instructions in the SF424 (R&R) Application Guide must be followed.  

    SF424(R&R) Senior/Key Person Profile

    All instructions in the SF424 (R&R) Application Guide must be followed. 

    R&R Budget

    All instructions in the SF424 (R&R) Application Guide must be followed with the following additional instructions:

    • Applications requesting multiple years of support must complete and submit a separate detailed budget breakdown and narrative justification for each year of financial support requested.
    • If an applicant is requesting indirect costs as part of their budget, a copy of the most recent Federal indirect cost rate or F&A agreement must be provided as part of the application submission.  This agreement should be attached to the RESEARCH & RELATED Other Project Information Component as line #12 'Other Attachments'.
    • If the applicant organization has never established an indirect cost rate and/or does not have a negotiated Federal indirect cost rate agreement, a de minimis indirect cost rate of 10 percent (10%) of modified total direct costs (MTDC) will be allowed.  MTDC means all direct salaries and wages, applicable fringe benefits, materials and supplies, services, travel, and subaward and subcontracts up to the first $25,000 of each subaward or subcontract.  MTDC excludes equipment, capital expenditures, charges for patient care, rental costs, tuition remission, scholarships and fellowships, participant support costs and the portion of each subaward and subcontract in excess of $25,000.
    • A portion of the budget should be reserved for travel to participate in site visits or attend meetings as requested by the FDA.   
    R&R Subaward Budget

    All instructions in the SF424 (R&R) Application Guide must be followed.

    PHS 398 Cover Page Supplement

    All instructions in the SF424 (R&R) Application Guide must be followed.  

    PHS 398 Research Plan

    All instructions in the SF424 (R&R) Application Guide must be followed. 

    Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

    • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

    Appendix:

    Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

    PHS Human Subjects and Clinical Trials Information

    The PHS Human Subjects and Clinical Trials Information form replaces the Human Subjects section of the Research Plan form. FOAs that do not allow clinical trials use this form for human subjects.

    When involving human subjects research, clinical research, and/or clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

    If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

    Study Record: PHS Human Subjects and Clinical Trials Information

    All instructions in the SF424 (R&R) Application Guide must be followed.

    PHS Assignment Request Form

    All instructions in the SF424 (R&R) Application Guide must be followed. 

    Foreign Institutions

    Foreign (non-U.S.) institutions must follow policies described in the HHS Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

    3. Unique Entity Identifier and System for Award Management (SAM)

    See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

    4. Submission Dates and Times

    Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

    Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, FDA's electronic system for grants administration. eRA Commons and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Late applications will not be accepted for this FOA.

    Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

    Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

    5. Intergovernmental Review (E.O. 12372)

    This initiative is not subject to intergovernmental review.

    6. Funding Restrictions

    All FDA awards are subject to the terms and conditions, cost principles, and other considerations described in the HHS Grants Policy Statement.

    Pre-award costs are allowable only as described in the HHS Grants Policy Statement.

    Additional funding restrictions may be part of the Notice of Award.  

    7. Other Submission Requirements and Information

    Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.  Paper applications will not be accepted.

    Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

    For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. For assistance with application submission, contact the Application Submission Contacts in Section VII.

    Important reminders:

    All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to FDA. See Section III of this FOA for information on registration requirements.

    The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

    See more tips for avoiding common errors.

    Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the assigned Grants Management Specialist and responsiveness by components of participating organizations, FDA. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

    Post Submission Materials

    Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

    Section V. Application Review Information
    1. Criteria

    Only the review criteria described below will be considered in the review process.

    Scored Review Criteria

    Reviewers will consider each of the review criteria below in the determination of scientific merit.

    Significance (20 Points)

    Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?  

    Investigator(s) (20 Points)

    Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?   

    Innovation (20 Points)

    Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?   

    Approach (20 Points)

    Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects? 

    If the project involves human subjects and/or FDA-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?  

    Environment (20 Points)

    Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?   

    Additional Review Criteria

    As applicable for the project proposed, reviewers will evaluate the following additional items, but will not give separate scores for these items and should not consider them in providing an overall score.

    Vertebrate Animals

    The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

    Biohazards

    Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

    Resubmissions

    Not Applicable

    Renewals

    Not Applicable

    Revisions

    Not Applicable

    Applications from Foreign Organizations

    Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

    Select Agent Research

    Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

    Resource Sharing Plans

    Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3)  Genomic Data Sharing Plan (GDS).

    Authentication of Key Biological and/or Chemical Resources:

    For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

    Budget and Period of Support

    Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

    2. Review and Selection Process

    Applications will be evaluated for scientific and technical merit by an Objective Review Committee using the stated review criteria.

    As part of the objective review, all applications:

    • Will receive a written critique.

    Appeals of objective review will not be accepted for applications submitted in response to this FOA.

    Applications will compete for available funds with all other recommended applications submitted in response to this FOA. The following will be considered in making funding decisions:

    • Scientific and technical merit of the proposed project as determined by objective review.
    • Availability of funds.
    • Relevance of the proposed project to program priorities.
    3. Anticipated Announcement and Award Dates

    Successful applicants will be notified of additional information that may be required or other actions leading to an award. The decision not to award a grant, or to award a grant at a particular funding level, is discretionary and is not subject to appeal to any FDA or HHS official or board.

    Section VI. Award Administration Information
    1. Award Notices

    A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

    Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

    Any application awarded in response to this FOA will be subject to terms and conditions found in the HHS Grants Policy Statement.

    2. Administrative and National Policy Requirements

    All FDA grant and cooperative agreement awards include the HHS Grants Policy Statement as part of the NoA.

    Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency.  HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

    HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

    In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), FDA awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements.  FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award.  An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS.  The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgment about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.”  This provision will apply to all FDA grants and cooperative agreements.

    FDA considers the sharing of research resources developed through FDA-sponsored research an important means to enhance the value and further the advancement of research. When research resources have been developed with FDA funds and the associated research findings published, those findings must be made readily available to the scientific community.

    Upon acceptance for publication, scientific researchers must submit the author’s final manuscript of the peer-reviewed scientific publication resulting from research supported in whole or in part with FDA funds to the NIH National Library of Medicine's (NLM) PubMed Central (PMC). FDA defines the author's final manuscript as the final version accepted for journal publication, which includes all modifications from the publishing peer review process. The PMC archive is the designated repository for these manuscripts for use by the public, health care providers, educators, scientists, and FDA. Please see the FDA Public Access Policy.

    Additional terms and conditions regarding FDA regulatory and FDA Center for Drug Evaluation and Research programmatic requirements may be part of the Notice of Award.

    Cooperative Agreement Terms and Conditions of Award

    The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (HHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and FDA grant administration policies.

    The administrative and funding instrument used for this program will be the cooperative agreement, an “assistance” mechanism (rather than an “acquisition” mechanism), in which substantial FDA programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, FDA's purpose is to support and stimulate the recipients’ activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities.  Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and FDA as defined below.

    2.A.1. Principal Investigator Rights and Responsibilities

    The PD(s)/PI(s) will have the primary responsibility for the scientific, technical, or programmatic aspects of the cooperative agreement and for day-to-day management of the project or program.  The PD(s)/PI(s) will maintain general oversight for ensuring compliance with the financial and administrative aspects of the award, as well as ensuring that all staff have sufficient clearance and/or background checks to work on this project or program.  This individual will work closely with designated officials within the recipient organization to create and maintain necessary documentation, including both technical and administrative reports; prepare justifications; appropriately acknowledge Federal support in publications, announcements, news programs, and other media; and ensure compliance with other Federal and organizational requirements.

    Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and FDA policies.

    Additionally PD/PIs will:

    1. Participate in site visits or attend meetings as requested by the FDA.  A portion of the budget should be reserved for such travel.

    2. FDA may also request data be made available through speaking engagements and publications, presentations at scientific symposia and seminars, while making sure that confidentiality and privacy of the data is protected. 

    3. The awardees will provide FDA any data obtained from investigations if requested by FDA. 

    4. Any publication or oral presentation of regarding outcomes of this grant must undergo FDA/CDER review and approval process. This process can take 30-90 days.

    2. A.2. FDA Responsibilities

    An FDA Project Officer (PO) will have substantial programmatic involvement as described below. The PO is the official responsible for the programmatic, scientific, and/or technical aspects of assigned applications and grants. The PO’s responsibilities include, but are not limited to, post-award monitoring of project/program performance, including review of progress reports and making site visits; and other activities complementary to those of the Grants Management Officer (GMO). The PO and the GMO work as a team in many of these activities.

    Additionally, an agency program official will be responsible for the scientific and programmatic stewardship of the award and will be named in the award notice.

    FDA will provide technical monitoring and/or guidance of the work, including monitoring of data analysis, interpretation of analytical findings and their significance.

    FDA will assist and approve (as deemed appropriate) the substance of publications, co-authorship of publications and data release.

    Financial Reporting:

    A. Cash Transaction Reports

    The Federal Financial Report (FFR) has a dedicated section to report Federal cash receipts and disbursements. For recipients, this information must be submitted quarterly directly to the Payment Management System (PMS) using the web-based tool. Quarterly reports are due 30 days following the end of each calendar quarter. The reporting period for this report continues to be based on the calendar quarter. Questions concerning the requirements for this quarterly financial report should be directed to the PMS.

    B. Financial Expenditure Reports

    A required Federal Financial Report (FFR) must be submitted annually. FDA now requires all annual financial expenditure reports to be submitted electronically using the Federal Financial Report (FFR) system located in the eRA Commons. This includes all initial FFRs being prepared for submission and any revised FSR/FFRs being submitted or re-submitted to FDA. Paper expenditure/FFR reports will not accepted.

    Annual FFRs must be submitted for each budget period no later than 90 days after the end of the calendar quarter in which the budget period ended. The reporting period for an annual FFR will be that of the budget period for the particular grant; however, the actual submission date is based on the calendar quarter. Failure to submit timely reports may affect future funding.

    Performance Progress Reporting:

    1.  Annual progress reports are required. The Annual Progress Report will be due as part of the Research Performance Progress Report (RPPR).

    2.  Grants with Multiple Years: When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR).

    Information regarding submitting the RPPR is available at https://era.nih.gov/erahelp/commons/default.htm#cshid=1020

    PROGRAM INCOME:

    1. The grantee is required to report any Program Income generated during the Project Period of this grant. Except for royalty income generated from patents and inventions, the amount and disposition of Program Income must be identified on lines 10 (l), (m), (n), and (o) of the grantee’s Federal Financial Report (FFR) SF-425.

    2. Examples of Program Income include (but are not limited to): fees for services performed during the grant or sub-grant period, proceeds from sale of tangible personal or real property, usage or rental fees, patent or copyright royalties, and proceeds from the sale of products and technology developed under the grant.

    3. Any Program Income generated during the Project Period of this grant by the grantee or sub-grantee is subject to the Addition Alternative for Program Income and, therefore, must only be used to further the goals of the project for which this grant was awarded.

    PRIOR APPROVAL:

    All requests that require prior approval must include the award number and bear the signature of an authorized official of the grantee business office as well as that of the PI/PD. Any requests involving funding issues must include a new proposed budget and a narrative justification of the requested changes. If a grantee questions whether prior approval is required for an activity or cost, they should contact the assigned Grants Management Specialist prior to expenditure of funds for clarification.

    Below are activities that require prior approval from FDA:

    CHANGE IN SCOPE OR OBJECTIVES

    CHANGE IN KEY PERSONNEL

    CHANGE IN GRANTEE ORGANIZATION

    DEVIATION FROM TERMS AND CONDITIONS OF THE AWARD

    CARRYOVER OF UNOBLIGATED BALANCES

    NO COST EXTENSIONS

    SIGNIFICANT REBUDGETING

    3. Reporting

    When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the Notice of Award.

    A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the HHS Grants Policy Statement.

    The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All awardees of applicable FDA grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. 

    In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

    Section VII. Agency Contacts

    We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

    Application Submission Contacts

    eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
    Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
    Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

    Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
    Contact Center Telephone: 800-518-4726
    Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
    Email: support@grants.gov

    Scientific/Research Contact(s)

    Eleftheria Tsakalozou, Ph.D.
    Office of Generic Drugs
    U.S. Food and Drug Administration (U.S. FDA)
    Telephone: 240-402-2726
    Email: Eleftheria.Tsakalozou@fda.hhs.gov

    Objective Review Contact(s)

    Shashi Malhotra
    Office of Acquisitions & Grants Services (OAGS)
    Food and Drug Administration
    Telephone: 240-402-7592
    Email: Shashi.Malhotra@fda.hhs.gov

    Financial/Grants Management Contact(s)

    Shashi Malhotra
    Office of Acquisitions & Grants Services (OAGS)
    Food and Drug Administration
    Telephone: 240-402-7592
    Email: Shashi.Malhotra@fda.hhs.gov

    Section VIII. Other Information

    All awards are subject to the terms and conditions, cost principles, and other considerations described in the HHS Grants Policy Statement .

    Authority and Regulations

    Awards are made under the authorization of Section 301 of the Public Health Service Act as amended (42 USC 241) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.

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