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

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Allergy and Infectious Diseases (NIAID)

National Institute of Mental Health (NIMH)

Funding Opportunity Title

Advancing Sustained/Extended Release for HIV Prevention (A-SER) (R01 Clinical Trial Not Allowed)

Activity Code

R01 Research Project Grant

Announcement Type

New

Related Notices

NOT-OD-19-128, Changes to NIH Requirements Regarding Proposed Human Fetal Tissue Research.

NOT-OD-19-137, Clarifying Competing Application Instructions and Notice of Publication of Frequently Asked Questions (FAQs) Regarding Proposed Human Fetal Tissue Research.

Funding Opportunity Announcement (FOA) Number

RFA-AI-19-063

Companion Funding Opportunity

None

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

 93.855, 93.242 

Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to stimulate the development of new and innovative sustained/extended release (SER) drug delivery systems (DDS) that can achieve extended durations (months to years) and provide systemic protection from all routes of HIV infection/transmission in at-risk individuals. This FOA focuses on the following scientific priority DDS: low-volume depots compatible with self-injection technologies, erosible/biodegradable implants including in situ forming implants, intrauterine delivery systems and transdermal delivery systems. Applications will require an industry partner.  Applications incorporating drugs that are already under development or approved for HIV prevention and/or treatment by their intellectual property/patent/license holder must involve these persons/entities in a meaningful and significant manner in the application through letters of support and/or other evidence of a substantial commitment.    

Key Dates
Posted Date

September 11, 2019

Open Date (Earliest Submission Date)

November 4, 2019

Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Date(s)

Only accepting applications for the AIDS Application Due Date listed below. 

AIDS Application Due Date(s)

December 4, 2019, by 5:00 PM local time of applicant organization. All types of AIDS and AIDS-related applications allowed for this funding opportunity announcement are due on the listed date.

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.

Scientific Merit Review

April 2020

Advisory Council Review

May 2020

Earliest Start Date

 July 2020

Expiration Date

December 5, 2019

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the Research (R) 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
    Purpose and Scope

    The objective of this FOA is to support the development of specific SER DDS with rheological and biophysical properties that address scientific gaps in DDS development for SER HIV prevention.  This FOA is limited to support of the development of the following DDS: low-volume depots compatible with self-injection technologies, erosible/biodegradable implants including in situ forming implants, intrauterine delivery systems (IDS) and transdermal drug delivery systems. The ultimate SER product should provide months to years of HIV prevention coverage, be reversible through removal of the DDS, while offering “set it and forget it” protection from HIV infection.  The SER DDS targeted by this FOA represent emerging approaches for delivery of SER HIV prevention strategies and are needed to enable users to more easily adhere to HIV prevention dosing regimens by reducing dosing frequency, enabling longer more effective durations of drug coverage.  For the purposes of this FOA, the target populations are ages 14 years and older males and females, including transgender and gender non-conforming populations desiring SER products to prevent HIV acquisition/transmission.

    Background

    For DDS that are dependent on individual user decisions to use or not to use, multiple behavioral and social factors (individual, cultural, stigma-derived, DDS-related, etc.) have been identified that can contribute to low prevention product adherence.  The results of numerous non-vaccine biomedical HIV prevention (nBP)  phase III clinical trials have demonstrated conclusively that both adolescents and adults, when required to use daily dosing or coital-associated (pre and/or post) dosing with gel or an intravaginal ring (IVR), encounter problems in maintaining adherence over longer timeframes. Multiple user behavioral and social factors (individual, cultural, stigma-derived, DDS-related, etc.) have been identified that can contribute to low adherence for prevention products.  Biological and pharmacological barriers may also play a role in the effectiveness of prevention strategies where individual use decisions control adherence and the pattern of drug use.  In vitro modeling and direct observed therapy pharmacokinetic (PK) studies of daily oral emtricitabine/ tenofovir disoproxil fumarate (TDF/FTC) pre-exposure prophylaxis (PrEP) have shown that with a daily pill-taking regimen approximately 28% adherence by men and 85% adherence by women are required to achieve active metabolite levels in the blood and mucosal tissues associated with efficacy.  To improve adherence and potentially reduce its impact on prevention strategies, the nBP field has begun to evaluate anti-HIV drugs with longer durations of action in an effort to reduce the impact of inconsistent drug use due to inconsistent adherence. The most advanced of these efforts are Phase III clinical trials of a q8 weeks injection of a nanocrystal formulation of the integrase inhibitor cabotegravir for HIV prevention in men (HPTN 083) and women (HPTN 084). Although injectable SER prevention strategies could potentially have a significant impact on the HIV pandemic by removing the need for frequent dosing, there is still room for improvement. There are several questions that remain to be answered as well as capabilities that may need to be incorporated into SER HIV prevention strategies. These include: the impact of excess drug exposure (drug burst) after dose initiation on safety and establishment of protection; the impact of periods of suboptimal drug exposure (PK tail, time during which drug drops below effective levels) on emergence of resistance; the safety implications of not being able to terminate dosing if adverse events occur when deviceless (e.g. injection) DDS strategies are used; creation of user-friendly dosing schemes (volume of injection, size/number of devices used/implanted, and placement); and methods for renewing the dose (site of drug application, surgical procedures and user friendly durations) that facilitate the decision to engage in the SER prevention strategy. Therefore, this FOA focuses on developing the next generation of SER DDS optimized not only for delivery of HIV prevention (PK, PD, etc.), but also for their interaction with the user (look and feel) to increase the potential for initial uptake and continued use.

    Research Objectives

    For the purposes of this FOA, sustained release is defined as continuous exposure to the anti-HIV drug from a DDS that is achieved using either a continuous release device or through creation of a tissue depot. Extended release is defined as providing protection from HIV infection/transmission for a longer duration resulting in more consistent exposure to the prevention drug. Combining these 2 concepts into an optimal DDS creates a SER strategy.

    This FOA supports development of only the following DDS for the indicated durations:

    • Low-volume self-injectables (depot and non-depot forming) optimized for delivery in a self-injector for 3 months or more.  Low volume is defined as a total injection volume (single site or multiple sites of less than or equal to 1.0 mL).
    • Erosible implants or in situ forming biodegradable implants/depots for 6 months or more.
    • A non-contraceptive intrauterine delivery system (IDS) that will deliver an antiviral for 3 years or more and that will provide systemic protection from HIV infection.
    • Transdermal patches (continuous use or short exposure depot-forming) for 1 month or more 

     
    The following areas of preclinical drug development and behavioral research may be proposed for any of the above DDS:

    • Development of single and combination drug SER strategies with the ability to protect against HIV infection/transmission/acquisition from all routes of HIV mucosal exposure: female reproductive tract (FRT), male genitourinary system (MGS), and/or gastrointestinal (GI) tract. 
    • Understanding the PK of SER products by mapping the characteristics of drug(s) release including: drug burst (initial and during biodegradation of the DDS), lag period (time to establish effective concentrations), PK tails (duration of drug exposure beyond the effective concentration), and forgiveness intervals (dosing intervals during which the drug/DDS must be renewed to maintain continuous efficacy).
    • Understanding the processes of DDS erosion and degradation, specifically its impact on drug PK during terminal erosion/degradation (terminal drug burst), the time to full DDS dissolution after drug exhaustion, and the impact of redosing in the presence of residual DDS on the user.
    • Understanding the potential for and identifying/characterizing drug-drug interactions (DDI) and drug/device interactions that could compromise the effectiveness of a SER DDS or maintenance/prevention medicines.
    • Understanding the impact of continuous antiviral drug delivery or DDS degradation products on tissue sites, such as activation of drug transporters, foreign body reactions (wound healing, acute and chronic inflammation, foreign body responses, etc.) and/or local and systemic distribution of drug to HIV target tissues.
    • Understanding Preferred User Characteristics (PUC), which will govern decisions made by individuals to use the SER strategy (look and feel), and whether to adopt and maintain use of longer duration strategies. For this FOA, PUCs are defined as the rheological/biophysical properties of the SER DDS that invoke user judgments/decisions resulting in first-use, subsequent-use or no-use and/or early termination.

    Responsive Areas of Research Interest

    Examples of the types of research responsive to this FOA include, but are not limited to:

    • SER DDS that provide systemic prevention of HIV replication and infection in both male and female animal models of HIV/SIV/SHIV infection.
    • Combination SER which deliver all drugs simultaneously from a single DDS. DDS which compartmentalize the drugs to address drug-drug interactions (DDI) and/or create different release rates are responsive.
    • Use of animal model PK, PD and toxicokinetic (TK) studies to support the proposed duration of use and safety of the SER DDS.  Of significant interest are PK studies that establish efficacy and safety relationships between plasma and GI, MGS, and FRT (upper and lower) tissues/secretions, lymphoid tissues, and dosing/implantation site drug concentrations.
    • Performance of PK/PD studies which characterize and optimize the lag, duration, PK tail, forgiveness interval and characterize and minimize the interval between drug exhaustion and full degradation of erosible/biodegradable DDS.
    • Use of novel polymers, nanotechnology, 3-D printing and other novel/emerging technologies to solve specific problems related to the responsive DDS, such as: DDI, duration of action, tissue/systemic distribution, safety, and/or efficacy.
    • Hypothesis-driven research focused on the impact of the SER drug on the FRT/MGS/GI tract, specifically on mucosal barrier and immune function as it relates to the safety/efficacy of the proposed SER drug product and DDS. This may include impact on drug transporters, inducible and non-inducible cellular drug-degradation and metabolism pathways, as well as the impact of the DDS/drug on epithelial cell function, mucosal wound repair, immune cell trafficking, and the impact of prolonged exposure of the drug on innate, adaptive and cellular immunity.  Histology of implant/depot sites that encompass the proposed duration of the DDS.  
    • PUC research focusing on identifying factors which may influence an individual’s choice to use, using behavioral and social science tools that measure user perceptions of the DDS, such as ethnographic studies, perceptibility assessments, mental modeling, user journeys, discrete choice and conjoint analysis. Research involving potentially prescribing physicians/health givers in the U.S. focusing on identifying attributes of the SER DDS, such as implant size, location and placement, that could negatively impact their willingness to provide the product.
    • Pilot manufacturing of the SER DDS to determine if the proposed SER DDS can be manufactured using Good Manufacturing Practices (GMP) quality guidelines.

    Industry Partner(s)

    Responsive applications will demonstrate substantial collaboration and participation in the proposed research of at least one industrial partner. An industrial partner/collaborator is broadly defined as an individual, group, or unit from a for-profit or not-for-profit pharmaceutical, biotechnology, bioengineering, or chemical company with an established expertise in product development. Substantive collaboration is defined as a significant commitment of one or more resources to the project including, but not limited to: personnel, provision of drug substance/product, product development support/guidance, provision of animal resources or laboratory models for testing, data management resources and/or regulatory support. Inclusion of a Contract Research Organization (CRO) to provide fee-for-service deliverables without significant participation/scientific collaboration in the research agenda does not meet the definition of an industry partner.
     
    Industry applicants are not required to involve collaborators from academic and/or non-profit research organizations, but are encouraged to do so, where appropriate. 

    SER Drug and DDS Intellectual Property/Patent/License Holder Involvement

    For SER DDS incorporating antiviral drugs or DDS that are already under clinical development or approved for HIV prevention and/or treatment by their intellectual property/patent/license holder, the applicant must involve these persons/entities in a meaningful way that results in a significant involvement in the proposed research.  Meaningful and significant involvement will be demonstrated by provision of documentation that identifies the role of the intellectual property/patent/license holder in the proposed research.  Evidence of commitment/involvement can be established through confidentiality, data sharing and material transfer agreements or similar approaches which outline the applicant’s access to the resource, data sharing process and communication plan that demonstrates participation and awareness of the intellectual property/patent/license holder in the proposed research and its projected outcomes.  A letter of support that does not address these criteria will not be considered adequate to demonstrate meaningful and significant involvement. 

    If the proposed DDS is protected by intellectual property/patent(s) covering a unique DDS architecture and/or component whose use is limited by such intellectual property/patent(s), then agreements with and participation by the intellectual property/patent/license holder of the DDS architecture/component will need to be demonstrated.

    Intellectual property/patent/license holder involvement and industrial partner requirements may be met by the same entity, but only if the requirements for both are met individually.

    Animal Models for Efficacy and PK Determinations

    Animal models to assess efficacy of the SER strategy should propose research in both males and females using well-characterized product to assess PK, efficacy and safety in both the FRT and GI tract.  Since MGS efficacy models are not as well developed, inclusion of MGS infection models is optional. 

    PUC Research

    This FOA will only support clinical research for assessing PUCs at a U.S. site. To meet the objectives of the FOA it is critical that proposed PUC study outcomes are linked and integrated into the proposed research and lead to and inform on the selection of SER DDS rheological/biophysical (look and feel) properties, and only research in which a DDS is handled to support “look and feel” assessments by participants are allowed, e.g. A mano studies.

    A mano research with prototype, over the counter (OTC) or licensed DDS may be proposed. Care should be taken when selecting SER DDS surrogates that the rheological/biophysical properties either span a range of potential user perceptions or match the biophysical/rheological properties of the proposed SER DDS.  

    All products used for A mano testing must be managed to minimize all potential safety risks for the participants.  Prototypes manufactured specifically for use in a PUC study must be manufactured under Good Manufacturing Practices (GMP) with appropriate stability, sterility and skin/dermal irritation testing post-manufacture.  For some prototypes there may be sufficient human safety data in humans to justify forgoing specific skin/dermal sensitization/irritation testing, e.g. drug-free silicone and ethylene-vinyl acetate (EVA) DDS.  Use of OTC or licensed products as surrogate products by study participants is allowed, if there are no documented handling safety risks and potential safety risks and allergic reactions are managed. Use of nonoxynol-9 (N-9) based or containing products will not be supported for PUC assessments. If repackaging of an existing prototype is proposed for a PUC study, stability in, sterility and package compatibility assessments must be performed.

    Timelines and milestones

    Milestones are required for this FOA. Applications will include timelines and milestones as measures of research progress toward the development of a SER DDS. Applications not including milestones and timelines will be considered incomplete and will not be reviewed.

    Non-responsive Areas of Research

    Applications proposing the following areas of research will be considered non-responsive and will NOT be reviewed:

    • Inclusion of any phase clinical trial(s).  Any form of human subject dosing or implantation.
    • Exposure of human subjects to a prototype or listened drug-containing DDS in PUC studies or conduct of PUC clinical research at a non-U.S. site.
    • Applications proposing development of SER DDS with durations of action that do not meet the minimal duration defined in the FOA or proposal of a non-priority DDS, e.g. non-erosible implant or depot, IVR, etc. 
    • Development of SER DDS containing any antiviral or DDS (when applicable) for which the applicant has not demonstrated participation of the drug intellectual property/license/patent holder in the application.
    • Strategies or antiviral candidates without demonstrated antiviral activity to HIV.  Incorporating antivirals selected specifically for creating a Multipurpose Prevention Technology SER DDS with activities against multiple sexually transmitted infections (STI).  Inclusion of drugs with activities against non-HIV sexually transmitted infection are not prohibited, but all proposed development and research must focus on the anti-HIV activity of the proposed SER DDS and not its anti-STI activity or properties.  This includes experimental designs where analysis of anti-STI activity is proposed on samples from animal models.   
    • Random, bulk or high-throughput screening of chemical or natural product libraries or collections to “discover” new anti-HIV candidates (discrete inhibitors or natural product mixtures) for incorporation into SER DDS. 
    • Medicinal chemistry efforts on new or previously described/licensed antivirals. Prodrug or chemical modifications of licensed antivirals for treatment or prevention to enable creation of or incorporation into a SER DDS.  This does not preclude using prodrugs if the intellectual property/patent/license holder provides the prodrug or the prodrug is developed in collaboration with the intellectual property/patent/license holder.  Medicinal chemistry efforts in this latter case should be supported by the intellectual property/patent/license holder.
    • Development of an uncharacterized or a complex-mixture natural product as the antiviral component of a SER strategy.
    • Broad, generalized global assessments/hypothesis-generating research in animal models or humans to identify biomarkers of SER drug/DDS impact on the FRT, MGS, or GI tract using genomic, proteomic, scriptomic, metabolomic, and/or microbiome analysis/technologies that do not directly support the development and/or characterization of the safety and/or efficacy of the SER DDS. 
    • Intravenous infusion of any component of a SER strategy.
    • Cure or amelioration of bacterial vaginosis (BV) or vaginal dysbiosis by any chemical or biological means to reduce HIV susceptibility as part of a SER strategy. This restriction includes replacement of abnormal microbiomes with "normal" bacteria by supplementation or transplantation as a method to modulate genital or GI micro- or macro-environments as a SER anti-HIV strategy.
    • SER strategies employing a female or male condom, and/or diaphragm. Use of a Copper or hormone containing IUD or IDS as the SER DDS.
    • Use of any live biotherapeutic or vector system (viral, bacterial, fungal, etc.) to produce/deliver the anti-HIV component of the proposed SER DDS. Development or optimization of a Genetically Modified Organism (GMO) as a part of a SER DDS or incorporation of bacteria selected or engineered to be antiviral for HIV. 
    • Use of non-specific agents/products/drugs/candidates as the anti-HIV component(s).  For this FOA non-specific agents are defined as agents that display broad anti-microbial activity (nonspecific killing of viruses, parasites, yeast, and pathogenic and/or beneficial bacteria) and/or do not have a defined anti-HIV target.  Non-specific anti-HIV inhibitors may be chemically characterized as detergents or sulfonated polymers that act as either viricidal agents or charge-based inhibitors of HIV entry.  Examples include, but are not limited to, N-9, BZK, C31G, and high molecular weight sulfonated polymers such as carrageenan, dextran sulfate, cellulose sulfate, and some dendrimers.
    • Development of SER products incorporating any of the following HIV antiretrovirals:
    • SER composed solely of or combinations of tenofovir (TFV, PMPA, (R)-9-(2-phosphonoylmethoxypropyl) adenine), tenofovir disoproxil fumarate (TDF or Viread®) and/or tenofovir alafenamide fumarate (TAF).
    • The non-nucleoside reverse transcriptase inhibitor dapivirine as a single agent or in combination with TFV, TDF, TAF or Emtricitabine (FTC).
    • Development of the following combination antiretrovirals as the anti-HIV component of a SER strategy: TFV, TDF or TAF combined with emtricitabine (FTC),
    • Incorporation of rilpivirine (TMC-278) or cabotegravir (GSK-744, GSK/S 1265744) singly or in combination as the anti-HIV component. Development of combinations of these drugs with other active pharmaceutical ingredients (APIs) are responsive when requirements for involvement of the intellectual property /license /patent holder are met.
    • Any lectin or non-lectin active pharmaceutical ingredients that targets glycosylation on virus or non-virus targets as a means to prevent HIV replication, such as Cyanovirin-N, Griffithsin and other high glycosylation/mannose lectin-binding HIV inhibitors or their derivatives.
    • Vaccine development of any form (new mucosal vaccine, vector, insert, or delivery system) and/or use of a vaccine as the antiviral or efficacy-enhancing element of a SER prevention strategy.
    • Basic behavioral research designed to develop and inform on broad issues of SER product use and uptake. Surveys and research designed to provide information on specific groups/ community/ individual attitudes/acceptability using hypothetical, conceptual or theoretical products. Education programs focused on any potential stakeholder population to support introduction of a SER product. Structural and/or behavioral interventions to enhance projected product use or to prepare for product roll-out or implementation. Research targeting individuals other than product users, such as policymakers, government officials or any non-user stakeholder to determine general enthusiasm/ openness to the product concept of a SER.  Research or modeling designed to assess the theoretical impact of a SER strategy on HIV disease or incidence.
    • GMP manufacturing of drug substance or drug product to support a future, ongoing or proposed clinical trial.  Inclusion of Investigational New Drug (IND) or Investigational Device Exemption (IDE) preparation/application activities and/or performance of animal studies to specifically support an IND/IDE submission.

    Applicants are encouraged to contact the Scientific/Research Contact(s) located at the end of this FOA to discuss planned strategies for developing an application.

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

    Section II. Award Information
    Funding Instrument

    Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

    Application Types Allowed

    New

    The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

    Clinical Trial?

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

    Need help determining whether you are doing a clinical trial?

    Funds Available and Anticipated Number of Awards

    NIAID intends to commit $3.8 million in FY 2020 to fund 3-5 awards.

    Award Budget

    Application budgets are limited to $600,000 in direct cost per year.

    Award Project Period

     The scope of the proposed project should determine the project period. The maximum project period is 5 years.  

    NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from 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 NIH 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 NIH 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. The NIH Policy on Late Submission of Grant Applications states that 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)– 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 to register in eRA Commons.  Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. 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 NIH 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 NIH 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 NIH will not accept duplicate or highly overlapping applications under review at the same time.  This means that the NIH 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.
    • An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).
    Section IV. Application and Submission Information
    1. Requesting an Application Package

    The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace 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 Research (R) Instructions in the SF424 (R&R) Application Guide, 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.

    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 IC 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), 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:

    Bruce Sundstrom, Ph.D.
    Telephone:  240-669-5045
    Email:  sundstromj@niaid.nih.gov

    Page Limitations

    All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

    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 or Modular Budget

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

    Do not request funds for medicinal chemistry or chemistry to create/develop prodrugs or to chemically modify antivirals for the purpose of incorporating into a SER DDS.

    Do not request funds for testing activity against STI(s) or experimental designs where analysis of anti-STI activity is performed.

    Travel funds may be requested for attendance at one scientific meeting per year by the PD(s)/PI(s).

    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, with the following additional instructions: 

    Research Strategy: Applicants must discuss how the proposed SER DDS represents an advancement beyond the products currently being developed. If the proposed SER DDS development approach/rationale relies on research in fields outside the current biology, pharmacology and pharmaceutical research and development of prevention products, the applicant should discuss their relevance to the proposed SER approach and how progress in these fields enables the proposed product.
     
    Describe the SER product development plans, including:

    • The rationale for selection of the specific drug (s) and DDS of the proposed SER, and how the proposed SER DDS addresses current scientific gaps in development of this DDS for SER use.
    • Discuss how the proposed SER DDS meets the requirement of providing systemic protection from HIV infection.  If this information will be validated in the proposed research, provide a description of the drug and DDS properties and research outcomes that will support this property.
    • Discuss how the proposed SER DDS achieves or exceeds the minimum FOA-required duration of action for that DDS.
    • Describe the forgiveness interval of the proposed SER strategy and how it will be verified experimentally. 
    • For erosible/biodegradable DDS describe how the time to full degradation of the DDS will be determined and its relationship to the drug-release profile. For erosible/biodegradable DDS describe the forgiveness interval in relation to the time to full degradation of the DDS.
    • Describe the potential for DDI and how they will be identified and dealt with.  If the anti-HIV strategy includes metabolic boosters, e.g. Cobicistat or other drug/metabolic enhancers designed to boost the anti-HIV efficacy of the antiviral drug, then the use of this strategy should be adequately described in the context of known effects of Cytochrome P450 modulation on the safety and efficacy of other drugs which may be used, e.g. hormone contraceptives and chronic disease treatment drugs.

    Animal Models for Efficacy and PK Determinations: Applications proposing animal model research should describe the design features incorporated into the study which promote understanding of the safety and systemic protection against virus infection/transmission (efficacy) in both male and female animals.  Describe the study design elements and features that support the integrity of the study endpoints, including descriptions of:

    • How the study features will confirm the FOA requirement for systemic protection from virus infection.
    • The positive control and placebo arms and their role in the study outcome.
    • How the drug products were characterized for stability, drug content and release prior to the planned animal study.
    • How time points for sample analysis were chosen.
    • How the tissues and secretions chosen for analytical testing were selected.
    • Describe the analytical assays to be used and their validation status providing lower limits of quantitation (LLOQ) where possible. 
    • Describe endpoints other than efficacy outcomes, e.g. colposcopy/endoscopy, histology of mucosa and injection/implant sites, microbiome analysis, etc., and their role in establishing the safety and/or efficacy of the SER strategy. 

     
    PK research: Describe the computational tools to be used for PK/PD analysis and/or to infer/characterize SER DDS PK features such as duration, lag, tail, and forgiveness. If PK modeling is used describe the analysis to be done.
     
    Use of genomic, proteomic, scriptomic, and/or microbiome analysis/technologies:  Describe how any proposed genomic, proteomic, scriptomic, and/or microbiome analysis/technologies and systems biology tools will be employed to address specific questions in a hypothesis-driven manner to inform on the SER strategy safety and efficacy. 
     
    PUC Research: If applicable, describe the design of the studies and how the outcome will support/guide the selection of rheological and biophysical “look and feel” properties of the SER DDS. Describe any preparation (manufacturing, repackaging, etc.) of prototypes to be used and how it supports safety for their A mano use.

    Industrial Partner:  Describe the role of the industrial partner in the development of the SER DDS, including the activities and processes that would not otherwise be available to the program.

    Applications derived solely from industry should describe the advantages that sole industry sponsorship brings to the application. If an academic collaborator is proposed in an application from an industry source, describe how the academic collaborator(s) is(are) integrated into the proposed research. If the industrial /pharmaceutical company is proposing a virtual effort (contracting out all or part of the research) describe the oversight and quality plans for the contracted elements of the plan.

    SER Drug and DDS Intellectual Property/Patent/License Holder Involvement: Provide a plan for engagement of the intellectual property/license/ patent holder in the proposed research and what resources will be provided by the intellectual property/license/ patent holder. Describe how this involvement will assist in the current and future development of the SER DDS strategy.  Describe how results of the research will be communicated to the intellectual property/license/ patent holder, and how intellectual property/license/patent holder input will be incorporated into the development plans for the SER strategy.


    Timelines and Milestones:  Applicants must propose timelines and milestones describing the research process and outcomes, respectively.  Timelines may be in the form of a Gantt chart.  Milestones can be integrated into the Gantt chart and do not need a separate section.  Milestones should address critical points for development and identify critical features of the proposed for SER DDS product.  Proposed milestones should contain quantifiable measures for success and not be a restatement of application Specific Aims.  Applicants MUST include Go/No-Go attributes/criteria in their milestones to identify critical parameters of the SER DDS development.

    Targeted Product Profile (TPP) (optional): In a clearly labeled figure or table, applicants may include a TPP to summarize SER drug product critical properties and targets for development. Describe the essential product attributes using optimal and minimally acceptable criteria for the drug and its DDS.   TPP product attributes may include duration of action, optimal dosing regimen, acceptable duration of PK lag periods and tails, maximum and minimum PK targets, forgiveness intervals, PD targets, stability and storage requirements, desirable physical and PUC-derived attributes, cold chain/storage requirements, etc.   The attributes identified in the TPP should identify a final product with the potential for advancement and ultimately licensure.
      
    GMP manufacturing: If studies to assess the suitability of the SER DDS for GMP manufacturing are proposed, describe the process to be undertaken and its essential nature to the development of the SER DDS as well as a rationale for inclusion in the proposed research.

    Letters of Support: If available, include letters of support/collaboration to demonstrate the involvement/commitment of an industry partner and/or the intellectual property, patent or license holder in the proposed research.

    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:

    Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide, with the following additional instructions:

    Include copies of any formal agreements or documents that establish the involvement/commitment of the intellectual property, patent or license holder in the proposed research.

    PHS Human Subjects and Clinical Trials Information

    When involving human subjects research, clinical research, and/or NIH-defined 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.

    Delayed Onset Study

    Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

    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 NIH Grants Policy Statement, and procedures for foreign institutions.

    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. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

    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, NIH’s electronic system for grants administration. NIH 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. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

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

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

    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 How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. 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 NIH. 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 Center for Scientific Review and responsiveness by components of participating organizations, NIH. 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 the policy. Any instructions provided here are in addition to the instructions in the policy.

    Section V. Application Review Information
    1. Criteria

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

    Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

    For this particular announcement, note the following:

    The NG-SER supports focused development of select DDS for the delivery of SER products.  Due to the nature of the responsive DDS and their status of development in the nBP field, the proposed research may be of higher than normal risk and, requiring novel scientific approaches and/or technologies to achieve the objective of developing DDS responsive to this FOA.  Therefore, applicants may have to rely on the inclusion of more extensive background material or general demonstrations of expertise in the area rather than the inclusion of extensive supporting preliminary data. Accordingly, the conceptual framework, the level of innovation, and the potential to significantly advance the targeted SER DDS may have more weight in establishing the overall merit of the proposed research, than comprehensive supporting preliminary data specific to the proposed SER DDS. 

    Overall Impact

    Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

    Scored Review Criteria

    Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

    Significance

    Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? 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?

    Specific to this FOA: Will the proposed approach to developing the SER DDS result in systemic protection from HIV infection and will the development and testing of the FOA responsive DDS help to establish the next generation of SER DDS in the pipeline?

    If the proposed SER development plan relies on fields outside traditional biology, pharmacology and pharmaceutical prevention products, is the strategy well supported and described within these fields?  Do the resources described provide a plausible basis for adaptation of the SER DDS approach to HIV prevention?

    If PUC research is proposed, is it well integrated into the proposed SER DDS development and will it inform on the rheological and biophysical properties of the envisioned SER DDS?

    Investigator(s)

    Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those 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?

    Specific to this FOA: Does the application adequately combine the expertise required in anti-HIV drug and DDS development to support the development of a SER product?
     
    Are the industrial partner(s) and their participation well integrated into the development of the proposed SER product?

    If the intellectual property/license/patent holder is different from the industrial partner(s), is the participation of the intellectual property/license/patent holder(s) well integrated into the development of the proposed SER product?

    If the Industrial partner and intellectual property/license/patent holder are the same person/entity does their participation adequately address both requirements?
       
    If academic investigators are included in an application led by industry, are they well integrated into the proposed research?

    Innovation

    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? 

    Specific to this FOA: Does the outlined development program embody innovation by leading to and supporting the creation of a new and innovative SER DDS and product(s) for HIV prevention which meets FOA requirements? Is the research and development outcome in line with the objective of creating the next generation of SER strategies?

    Approach

    Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed 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 NIH-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 individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?  

    Specific to this FOA: Does the overall SER development strategy adequately address the required PK parameters for duration, lag, forgiveness, and tail in developing an effective dosing regime and the potential for DDI? Are the analytical analyses and durations of animal research proposed adequate to quantitate the antiviral component in secretions and/or tissues of the FRT, MGS, and GI tracts and at dosing sites?  Are the validation status and lower limits of quantitation (LLOQ) of the analytical assays provided, where possible, and of sufficient sensitivity to support the proposed PK analysis?  Are the PK tools and modeling proposed for analysis of PK data sets appropriate for the proposed analysis? 

    If an erosible or biodegradable DDS is proposed is the release of the incorporated drug in sync with the degradation of the DDS?  Has the interval between full drug release and degradation of the DDS been optimized?  If the interval is significantly longer than the proposed forgiveness interval has its impact on redosing and user preferences (PUC) been addressed? 

    Will the proposed SER DDS provide systemic protection from all routes of HIV infection in both sexes?  And, does the design of the proposed animal research address this requirement?

    Have the investigators appropriately secured the participation of the intellectual property/license/patent holder for the SER antiviral and/or DDS to be used in the proposed research?  Through letter(s) of support and other documentation does it appear that the partner will actively participate in the research? Has the investigator developed a communication plan that involves the intellectual property/license/patent holder in the proposed research?  If the industrial partner and intellectual property/license/patent holder are the same entity has this been adequately justified and are all requirements met?

    If the applicant proposed PUC research are the proposed PUC study outcomes linked and integrated into proposed DDS development?  Will the selected rheological/biophysical properties of the prototype, OTC or licensed DDS used for PUC research inform on the selection of the rheological/biophysical properties of the targeted DDS?  Has participant risk for PUC research been managed and are appropriate safety and manufacturing controls in place for any manufactured prototype(s) or repackaged OTC products used?

    If the application uses preliminary data or experimental approaches derived from an alternative research field (e.g. topical microbicides, contraception research, DDS development in cancer, Alzheimer's, Parkinson's disease, diabetes, etc.) to justify development, do the information and preliminary data support its porting to SER for HIV prevention?
     
    If the applicant is using contractors to provide research support for SER development is/are there plan(s) for management and quality oversight of the contractors?
     
    Are the proposed milestones and timelines well-integrated into the overall research strategy and SER DDS development plan?  Are the milestones provided appropriate, feasible, quantifiable and achievable within the proposed time-frame of the research elements they support? Are the Go/No-Go criteria appropriate for the described testing and integrated into the milestones?

      If a TPP is provided, does the TPP adequately identify physical, biological and rheological features of the proposed SER DDS product, identifying optimal and minimally acceptable criteria for the identified attributes?  Are the TPP identified properties achievable, and do they describe a commercially viable/licensable SER product?

    If pilot GMP manufacturing is proposed, are the scope of objectives of the pilot GMP effort adequately described and is GMP manufacturing necessary for the proposed development pathway?

    Environment

    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? 

    Specific to this FOA:  Are the required HIV prevention and DDS-development resources available to the project? Are the environment and resources provided by the industrial partner well-integrated into the project to ensure a successful outcome?  Are real or intangible resources provided by the intellectual property/license/patent holder integrated into the research plan?
     

    If the application is derived solely from an industrial /pharmaceutical company, are the physical resources adequately described?  If the industrial/pharmaceutical company is proposing a more virtual effort (contracting research), are the plans appropriate to oversee the development plan?

    Additional Review Criteria

    As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

    Protections for Human Subjects

    For research that involves human subjects but does not involve one of the  categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

    For research that involves human subjects and meets the criteria for one or more of the  categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

    Inclusion of Women, Minorities, and Individuals Across the Lifespan 

    When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

    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

    Additional Review Considerations

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

    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) appropriate Scientific Review Group(s) convened by the National Institute of Allergy and Infectious Diseases, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

    As part of the scientific peer review, all applications:

    • May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
    • Will receive a written critique.

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

    Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Allergy and Infectious Diseases Council. The following will be considered in making funding decisions:

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

    After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

    Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

    Section VI. Award Administration Information
    1. Award Notices

    If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

    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 on the Award Conditions and Information for NIH Grants website.  This includes any recent legislation and policy applicable to awards that is highlighted on this website.

    Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

    2. Administrative and National Policy Requirements

    All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

    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.

    For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. 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 https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html.  Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.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), NIH 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 judgement 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 NIH grants and cooperative agreements except fellowships.

    Cooperative Agreement Terms and Conditions of Award

    Not Applicable

    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 NIH Grants Policy Statement.

    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 NIH 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 NIH 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.  See the NIH Grants Policy Statement for additional information on this reporting requirement.

    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, application errors and warnings, documenting system problems that threaten submission by the due date, and 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)

    General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
    Email: GrantsInfo@nih.gov (preferred method of contact)
    Telephone: 301-945-7573

    Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
    Contact Center Telephone: 800-518-4726
    Email: support@grants.gov

    Scientific/Research Contact(s)

    Jim A. Turpin, Ph.D.
    National Institute of Allergy and Infectious Diseases (NIAID)
    Telephone:  301-451-2732
    Email:  jturpin@niaid.nih.gov

    Theresa Senn, Ph.D.
    National Institute of Mental Health (NIMH)
    Telephone: 301-761-7852
    Email: teri.senn@nih.gov

    Peer Review Contact(s)

    Bruce Sundstrom, Ph.D.
    National Institute of Allergy and Infectious Diseases (NIAID)
    Telephone:  240-669-5045
    Email:  sundstromj@niaid.nih.gov

    Financial/Grants Management Contact(s)

    Ann Devine
    National Institute of Allergy and Infectious Diseases (NIAID)
    Telephone:  240-669-2988
    Email:  adevine@niaid.nih.gov

    Rita Sisco
    National Institute of Mental Health (NIMH)
    Telephone: 301-443-2805
    Email: rita.sisco@nih.gov

    Section VIII. Other Information

    Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

    Authority and Regulations

    Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.

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