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)

Funding Opportunity Title

Integrated Preclinical/Clinical Program for HIV Microbicides and Biomedical Prevention (IPCP-MBP) (U19)

Activity Code

U19 Research Program – Cooperative Agreement

Announcement Type

New

Related Notices
  • June 4, 2014 - This RFA has been reissued as RFA-AI-14-025.
Funding Opportunity Announcement (FOA) Number

RFA-AI-13-023

Companion Funding Opportunity

None

Number of Applications

See Section III. 3. Additional Information on Eligibility.

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

93.855, 93.856

Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to support integrated and iterative multi-project, multi-disciplinary preclinical development and exploratory clinical studies with the goal of advancing, strengthening and maintaining an innovative pipeline of non-vaccine biomedical prevention (nBP) strategies, including microbicides, PrEP, and Multipurpose Prevention Technologies (MPT). The focus of the IPCP-MBP is to stimulate and support a strong, diverse base in preclinical discovery and development of nBP candidates that includes development of single and combination nBP delivered pericoitally and by sustained delivery systems to the male and female genital and gastrointestinal (GI) tracts to prevent HIV acquisition/transmission. This objective will be accomplished by supporting the translation of candidates and strategies from preclinical to pre-Phase I clinical studies delivered by a variety of drug delivery systems (DDS), including gels, films, quick dissolving tablets, intravaginal rings (IVR), implants, oral, injection and MPT-based DDS strategies. This FOA has significant modifications to previous offerings of the Integrated Preclinical Clinical Program. Applicants are urged to read the FOA carefully.

Key Dates
Posted Date

June 24, 2013

Open Date (Earliest Submission Date)

October 13, 2013

Letter of Intent Due Date(s)

October 13, 2013

Application Due Date(s)

November 13, 2013, by 5:00 PM local time of applicant organization.

AIDS Application Due Date(s)

November 13, 2013 by 5:00 PM local time of applicant organization.

Scientific Merit Review

March, 2014

Advisory Council Review

May, 2014

Earliest Start Date

July, 2014

Expiration Date

November 14, 2013

Due Dates for E.O. 12372

Not Applicable  

** ELECTRONIC APPLICATION SUBMISSION REQUIRED**

NIH’s new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically; paper applications will not be accepted. ASSIST replaces the Grants.gov downloadable forms currently used with most NIH opportunities and provides many features to enable electronic multi-project application submission and improve data quality, including: pre-population of organization and PD/PI data, pre-submission validation of many agency business rules and the generation of data summaries in the application image used for review.

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) and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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.

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

The National Institute of Allergy and Infectious Diseases (NIAID) invites applications from single institutions and consortia of institutions to participate in the Integrated Preclinical/Clinical Program for HIV Microbicides and Biomedical Prevention (IPCP-MBP). The purpose of this FOA is to support integrated and iterative multi-project, multi-disciplinary preclinical development efforts and exploratory clinical studies with the goal of advancing, strengthening and maintaining an innovative pipeline of non-vaccine biomedical prevention (nBP) strategies, including microbicides, PrEP, and Multipurpose Prevention Technologies (MPT). The purpose of the multi-project and core environment of the IPCP-MBP is to stimulate and support a strong, diverse base in preclinical discovery and development of nBP candidates that includes development of single and combination nBP delivered to the male and female genital and gastrointestinal (GI) tracts to prevent HIV acquisition/transmission. The purpose will be accomplished by supporting the translation of candidates and strategies from preclinical to pre-Phase I clinical studies delivered by a variety of drug delivery systems (DDS), including gels, films, quick dissolving tablets, intravaginal rings (IVR), implants, oral, injection and MPT-based DDS strategies. A minimum of two research projects and an Administrative Core must be proposed. At least one component (research project or Scientific Core) must be from a private sector for-profit or not-for-profit company. The proposed research is not required to include a pre-Phase I clinical trial or provide comprehensive coverage for all activities that might be required to develop a specific candidate or strategy for advancement to clinical trials.

NOTE: While pre-Phase I clinical trials conducted within the continental United States (U.S.) are responsive, Pre-Phase I clinical trials proposed to be conducted at non-U.S. sites will not be supported under this FOA. This FOA will not support any clinical trials (Phase I, II or III) that do not meet the definition of a pre-Phase I clinical trial (below). Applicants are encouraged to seek other sources of support for traditional Phase I, II, or III clinical trials and the production of drug substance and products required to support them.

Background

With current global HIV infection estimates exceeding 42 million people, the development of a safe, effective, and acceptable nBP strategy to prevent the sexual transmission of HIV could play a major role in reduction of the over 7,000 new HIV infections world-wide per day, potentially saving millions of lives. nBP candidates are chemically defined agents/drug/active pharmaceutical ingredients (API), peptides, proteins which when applied to the female and/or male genital and/or the gastrointestinal (GI) tract can result in inhibition of HIV acquisition/transmission. nBP may be delivered as pericoital prevention (gels, films, quick dissolve tablets or other DDS systems) or by sustained delivery systems (intravaginal ring (IVR), injection, implant or oral.

The nBP field has changed dramatically from 2010 to 2013 as proof-of-concepts for nBP-mediated prevention have been obtained for gel-based topical microbicides and oral PrEP. Clinical trials have established that antiretroviral-based strategies can prevent HIV acquisition/transmission in women, discordant partners and men who have sex with men (MSM). However, with these proof-of-concepts have come additional questions regarding nBP PK, PD, and adherence, creating the need to not only understand nBP from the point of view of creating and maintaining a sustainable pipeline of nBP products, but also to develop methods to optimize dosing and monitor product use. Thus, the field of nBP is transitioning away from the need to focus solely on searching for better candidates to maintain a sustainable pipeline of nBP candidates and strategies toward needing deeper understandings of the underlying biological, pharmacological, biophysical and behavioral factors controlling HIV prevention strategy safety, efficacy, acceptability and adherence.

The NIAID/DAIDS IPCP Program for HIV Topical Microbicides (IPCP-HTM) has a history of supporting the transition of topical microbicide candidates from early discovery to initial clinical testing, and creating integrated platforms that promote collaborative research to meet the many challenges arising in the rapidly changing field of topical microbicides. The evolution of the IPCP-HTM program into the IPCP-MBP will continue this effort and expand it to address emerging challenges in the development of safer, more effective and acceptable microbicide, PrEP and MPT candidates and strategies.

Research Objectives and Scope

The scientific and nBP development objectives of the IPCP-MBP are to:

For the purposes of this FOA, coital prevention will be defined as delivery of an nBP candidate or strategy 24 h before or after intercourse with the intent of preventing HIV transmission. Pericoital prevention will be used synonymously with "pericoital release" and will be defined as the delivery of an nBP agent which provides protection from HIV infection for at least 1 week around application. Pericoital application may be continuous or episodic and application may occur before, during or after coitus. Sustained prevention will be used synonymously with "sustained release", and will be defined as delivery of an nBP agent where dosing to establish protection is disassociated from coitus, and provides protection from acquisition/transmission of HIV for a minimum of 1 month.

The scope of work appropriate for support includes strategies developed around single and/or combination nBP approaches that prevent HIV transmission/acquisition through interaction with well-described or novel anti-HIV (gp120, gp41, RT, etc.) or cellular targets (CD4, CCR5, etc.). The candidate’s proposed mechanism of action should be compatible with the concept of prevention of HIV acquisition/transmission. Strategies employing modulation of innate and adaptive immunity or inflammatory processes as part of an nBP strategy or HIV prevention are also of interest.

An innovative approach is critical for enabling advancement of nBP candidates and strategies within the context of an IPCP-MBP program. However, in the case of the IPCP-MBP, innovation may be realized and be a function of the cumulative impact of the individual projects and/or scientific cores on the nBP field, which would not be realized by the efforts of the individual cores or projects outside the IPCP-MBP program.

Applications are required to be designed as a platform for support of integrated and iterative research and development projects and cores that facilitate advancement of nBP toward clinical testing. Activities supported by the IPCP-MBP may include, but are not limited to, preclinical virology and toxicology assessments of lead candidates; development and validation of Good Laboratory Practice (GLP)-compliant analytical assays; performance of GLP vaginal, rectal and/or systemic toxicokinetic and safety studies, performance of pharmacokinetic (PK) and pharmacodynamic (PD) studies, and Good Manufacturing Practice (GMP)-manufacturing activities, and exploratory small scale pre-Phase I clinical trials. Applications may also include research that is designed to advance the field of nBP prevention science by addressing critical research questions central to the development of a safe, effective and acceptable nBP candidate or strategy. Applications may include any combination of these activities and/or the development of combination strategies incorporating multiple modes of biomedical prevention, i.e. microbicides and PrEP. Applications may also include the development of MPT strategies that may be composed of combinations of HIV and Sexually Transmitted Infection (STI) inhibition strategies, where there is documented evidence that the STIs increase susceptibility to HIV transmission or licensed contraceptive methods.

The IPCP-MBP, through the value-added aspect of the integrated multi-project environment, will support innovative research and development projects in the following four areas:

1. nBP field enhancement: Although the overarching goal of the IPCP-MBP is to advance novel prevention approaches toward clinical studies, hypothesis–driven projects with a potential impact broader than a specific prevention strategy can also play an important role in a proposed IPCP-MBP program. These projects may be designed to address hypotheses that are central to the IPCP-MBP field, with the knowledge gained adding significantly to the advancement of the candidate or strategy that is the thematic basis for the IPCP-MBP application.

All proposed research needs to be carried out in the context of an identifiable anti-HIV candidate(s) or strategy(ies) with the outcomes of the research directly supporting the advancement of the candidate or strategy forming the thematic basis of the application.

Examples of responsive nBP development projects include the role of the vaginal/rectal microenvironment components/conditions such as: sexual trauma, biofilms, age, hormone changes, exogenous hormone use, mucus, vaginal fluid factors, semen/seminal plasma, leukocyte trafficking, adaptive or innate immune factor expression and elucidating of the role of inflammation in the safety and efficacy of nBP products. nBP development projects may also include the development and validation of new technologies, i.e. novel sustained release formulation strategies, electronic or other methods of monitoring or quantifying product adherence, and novel animal and/or human safety assessment techniques.

Research projects should be focused on advancing a specific candidate or strategy. Studies focusing solely on the basic research of HIV transmission and/or basic/general candidate discovery will not be supported under this FOA.

2. Preclinical Development: These projects need to focus on preclinical development of nBP candidate(s) and/or strategies and the DDS used to deliver them. The objectives of a preclinical development project are intended to (a) prove the feasibility of the candidate/strategy, and (b) meet minimal requirements for preclinical virology as identified by the Food and Drug Administration (FDA) (http://www.fda.gov/OHRMS/DOCKETS/98fr/05d-0183-gdl0002-01.pdf and draft Guidance for Industry Vaginal Microbicides: Development for the Prevention of HIV Infection

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM328842.pdfads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM328842.pdf).

For the purposes of this FOA, feasibility of a prevention candidate or delivery system is defined as the demonstration of one or more properties compatible with:

If more than one candidate or delivery system is being developed or superiority determined, preclinical studies are expected to be incremental and iterative in nature, resulting in down-selection to an optimized prevention candidate or DDS. The proposed studies should be developed such that a strong scientific rationale can be established for use of the candidate and proposed DDS in the male and/or female genital and/or GI tracts to prevent HIV transmission/acquisition. Applicants are encouraged to include preliminary studies, that may not meet the rigorous requirements of GLP IND-enabling critical path studies, but may provide down-selection enabling decisions, such as assessments of toxicity (acute and/or chronic), immunogenicity of protein and peptide candidates, potential toxic effects on the immune system (immunotoxicity), PK/PD determinations and compatibility with, stability in and release from proposed delivery systems (formulations and devices).

IPCP-MBP preclinical projects are encouraged to develop and implement a Targeted Product Profile (TPP) that specifies the targeted properties and release rates from DDS.

3. IND-enabling Critical Path Project: This type of project focuses on enabling clinical testing of the nBP candidates, either through performing proposed pre-phase I trial(s) or by obtaining regulatory approvals to conduct a future clinical trial outside the current IPCP-MBP application. The overarching objective of the IND-enabling critical path project will be to enable regulatory approval for clinical studies by meeting the regulatory requirements for an Investigational New Drug (IND), Investigational Device Evaluation (IDE) and/or New Device Exception (NDE) application. To achieve the overarching goal it will be critical for the proposed studies to answer whether a proposed candidate can meet the regulatory requirements to enable clinical testing. .

This type of development is not strongly hypothesis–driven, is costly to perform, and involves performance of highly structured and controlled studies designed to meet federal code of regulations and/or International Conference on Harmonization (ICH) guidelines governing preclinical and clinical testing. The final selection and design of the studies required to meet regulatory requirements may require consultation with the U. S. Food and Drug Administration (FDA). The nBP drug product testing, production and delivery approaches proposed within the IPCP-MBP application may require iterative testing, and include many types of assessments some of which are: acute and chronic toxicology in rodent and non-rodent models, pharmacokinetic [absorption, distribution, metabolism and excretion (ADME)], pharmacodynamic studies (PK, PD and toxicokinetic studies), development of a clinical dosage form (formulation), ISO 10993 compliant extractable/leachable studies from nBP delivery devices, reproductive toxicology, genotoxicity, analytical method development/validation and studies to address Chemistry, Manufacturing and Control (CMC) requirements for a proposed active pharmaceutical ingredient (API) and its delivery vehicle. All IND-Enabling Critical Path Project studies should be conducted to be compliant with applicable United States Pharmacopeia (USP), GLP and GMP regulations.

Since many of the required studies will need to be performed by contract research organizations (CRO) with experience in the conduct and management of GLP and GMP compliant studies, plans for quality management and oversight will need to be outlined in the application. The oversight may take the form of quality audits and on-sight observations of animal handling, dosing and necropsy.

Applicants are encouraged to acknowledge considerations of cost of goods and feasibility of GMP production in the context of advancement of the nBP strategy to future clinical testing and licensure. NIAID recognizes that a proposed IND-enabling critical path project may not be all inclusive in its scope, but requires that the project support a proposed IND submission or planned Pre-phase I clinical trial.

Proposed IND-enabling critical path projects must  meet the following requirements:

4. Pre-Phase I Exploratory Clinical Development: Inclusion of pre-Phase I clinical trials allow the pursuit of nBP-derived clinical hypotheses that are critical to the advancement of a specific product or DDS and/or are broadly applicable to nBP development. The pre-Phase I trial concept is unique to the IPCP-MBP Program.

The pre-Phase I clinical trial proposed in an IPCP-MBP application is not a traditional Phase I dose-escalation, safety, and tolerance study, that would ordinarily be used to initiate a clinical drug development program. The proposed clinical strength of the nBP under study may be used in the trial; however, pre-Phase I trials may only involve limited human exposure to products with commensurate numbers of subjects (not more than 20 per arm) and be low risk to the participants. It is not the intent of the pre-Phase I clinical trial to provide powered statistical assessments of the safety of the nBP candidates or strategies, but to support hypothesis generation, provide an initial determination of whether additional (more adequately powered) trials are warranted and/or be a test bed for new nBP hypothesis and analysis technologies. All trials will incorporate an appropriate suite of primary and secondary clinical safety endpoints and behavioral assessments, if appropriate. It is expected that exploratory objectives will be incorporated into the trial design that will inform on the nBP candidacy and/or advance the nBP field by providing new insights into the candidate and/or delivery system. In the case of sustained release strategy testing, time of exposure and risk will need to be balanced to maintain an overall low-risk for subjects with appropriate safety controls in place, such as limiting initial exposure before repeated or prolonged exposures are tested.

Traditional phase I and phase II and III trials are not responsive to the IPCP-MBP FOA, and applications containing these trials will not be supported under this FOA. Additionally trials which fail to address the requirements above will not be supported under this FOA.  Examples of responsive clinical projects include but are not limited to:

Studies may include HIV-positive cohorts, specific at-risk populations, such as adolescents, post-menopausal women, specific ethnicities, intravenous drug users (IDUs) and alcohol users and abusers when scientifically appropriate and within the scope of a pre-Phase I clinical trial.

Clinical projects may be proposed to start, i.e. initiate enrollment, as early as year 1, but no later than the end of year 4 of the 5 year project period.

Applicants should not propose or depend solely upon NIAID DAIDS-supported clinical trial networks to perform proposed IPCP-MBP clinical Phase I studies supported under this FOA. Collaboration with NIAID DAIDS-supported clinical trial networks is acceptable; however, the IPCP-MBP awardee must assume primary responsibility for the cost, planning, conduct of the proposed trial(s), and must not exceed the pre-Phase I clinical trial limitations identified above.

At the completion of the clinical trial an International Conference on Harmonization (ICH) E3report must be submitted to the appropriate regulatory agency(s) and the NIAID Program Officer.

Pre-Phase I clinical trials may not be conducted outside the continental U.S. A clinical trial is defined as a prospective study of human subjects designed to answer questions about biomedical or behavioral interventions, e.g., investigational drugs or investigational medical devices, or new ways of using known treatments. This definition encompasses any study that proposes to provide a licensed or unlicensed nBP or DDS to men or women as part of a proposed trial. Clinical research (research conducted on human subjects or material of human origin that can be personally identified) may be conducted outside the U.S. In this later case, expertise and qualifications required for international shipping of biohazardous products and evidence of arrangements with authorized officials allowing shipment of biological samples for any analysis proposed outside of the country of sample origin are needed. If analysis of clinical research obtained secretions, blood and/ or tissues are to be conducted at the foreign site the applicant is encouraged to provide evidence of adequate research infrastructure and site personnel training to conduct the proposed studies. Use of IPCP-MBP funds to develop infrastructure at foreign sites will not be supported, however resources may be used to qualify or validate site resources for quality endpoint detection.

Quality Use of Animal Models:

Applicants may include research that uses animal models such as humanized mouse and/or nonhuman primates (NHP) for safety and/or efficacy determinations of the nBP strategies or candidates. For the purposes of this FOA, animal studies are divided into two types. The first are studies that address the basic and developmental science issues of virus transmission within the context of the nBP candidate or strategy. Examples are assessments of environmental and physiological factors resulting from nBP exposure that might alter susceptibility, acquisition and dissemination of virus at the mucosal tissues. These include modeling sexual trauma, endogenous hormone state, use of exogenous hormones, inflammation, pregnancy, age and immune status. The second category is the use of animal models for screening/testing candidates to support their plausibility as clinical candidates. For this latter case, the recent trends of (1) investigator use of animal studies as “gateways” for clinical selection and establishment of biological plausibility in the absence of a requirement for demonstration of animal model efficacy by the FDA, (2) the cost of using these resources as “screening tools”, (3) limited availability of some species of animals and (4) the cost of producing and maintaining some animal species/subspecies/models for relevant experimental periods have led the NIAID/DAIDS prevention program to make specific recommendations regarding these types of studies.

The NIAID/DAIDS prevention program strongly encourages investigators proposing the use of animal efficacy models to support or prioritize candidates for clinical development to design robust experiments for assessing efficacy and safety of nBP. Robust experiments are defined as studies that: (1) include superiority assessments (selecting best candidate or more potent candidate) with positive control and/or placebo arms, (2) use sufficient numbers of animals in all groups to allow for powered statistical analysis of study endpoints, similar to those used for human clinical studies, and (3) use a formulated product. Applicants are cautioned that inclusion of too few animals in groups or failure to adequately justify the number of animals to be used can significantly reduce enthusiasm of the study section for the animal studies and overall application. It is also recommended that formulated products be used and that studies testing efficacy of a product delivered from a DDS have established product stability, retention of antiviral activity and release from the DDS prior to initiating the study. Studies in which unformulated prevention candidates are mixed in vehicles without establishing some level of stability or release from the vehicle are strongly discouraged in this FOA. The proposed animal studies, wherever possible, are encouraged to include additional study endpoints such as PK and PD determinations and safety measurements (colposcopy, histology, monitoring of vaginal pH, microflora analysis and/or measurement of adaptive/innate immune factors, etc.).

Milestones

Industry Partnerships

Responsive Areas of Research

All examples of responsive areas of research assume that the identified activities are being conducted in the context of advancing the thematic IPCP-MBP candidate or strategy. Responsive areas include, but are not limited to:

Non-responsive Areas of Research

Applications focusing or including on the following areas will not be considered responsive and will not be reviewed:

Administrative Core (required):

Each application must include an Administrative Core headed by the contact PD/PI. An Administrative Core is a resource to the multi-project/core grant, providing for the overall management, coordination and supervision of the Program. A steering committee composed of the leaders for each Project and Core chaired by the Administrative Core PD(s)/PI(s) will oversee the routine management and coordination of the IPCP-MBP award. The Administrative Core administers the plan provided in the application addressing the short- and long-term management of the program, including the TPP, if used. The Administrative Core must specifically address communications, group meetings, website development, teleconferences, scientific meeting presentations and publication of data, program internal sharing of information and shipping of reagents, demonstrate awareness of development progress and outcomes of other projects within the program, identify and resolve scientific personal and dispute problems, and engage the Scientific Advisory Panel (SAP) and NIAID as appropriate. Since IPCP-MBP Programs involve potentially complex interactions among multiple investigators and institutions, the Administrative Core needs to demonstrate its potential for leadership by describing processes and procedures that address routine activities such as shipping and control of reagents, publication policies and dispute resolution, as well as discuss its preparedness to deal with unexpected outcomes, such as delays in the finalization of inter-institutional agreements, delays in initiating Go/ No-Go animal and/or clinical studies, and changes in leadership of the IPCP-MBP award, projects and/or cores.

Applicants are encouraged to identify a program manager for routine daily management and communication within the proposed IPCP-MBP program.

Scientific Core(s) (optional):

A Scientific Core is a resource to the multi-project grant and inclusion of Scientific Cores is at the discretion of the applicant. Scientific Cores must support at least two of the proposed research projects. The application must indicate the specific projects to be served by the Scientific Core(s). The application will describe the facilities, techniques, and skills that the core will provide and describe the role of the Scientific Core Leader and each of the key participants.

The activities of Scientific Cores may not overlap with those of a proposed project. Scientific Cores are meant to be designed to provide broad-based support for routine activities that individual projects may need to facilitate their development activities. If an activity is being performed in a project and other projects may need access to that activity, consider removing the activity from the project and creating a core, making the project a core, or developing a plan for access to the project resources rather than creating a core that duplicates IPCP-MBP activities. Examples of Scientific Cores include performance of in vitro and in vivo screening/testing algorithms, and statistical, data management, and regulatory support for IND-enabling critical path projects and pre-Phase I clinical trials. Applicants can propose Scientific Cores to conduct activities that are typically associated with the IND-enabling process, i.e. manufacturing, performance of GLP and GMP activities. However, these cores are not eligible for the IND-enabling critical path project funds. Scientific Cores devoted solely to coordinating contractual activities to support preclinical development of a nBP, such as those associated with fee-for-service support, i.e. GLP toxicology, GMP manufacturing, etc., are strongly discouraged. These activities in the absence of a Regulatory Core are best coordinated within individual research project(s) and/or the Administrative Core.

Applicants are encouraged to create a Regulatory Core to assist in meeting the NIAID/DAIDS administrative and FDA requirements for conducting a clinical trial.

NOTE: Pre-Phase I clinical trial(s) may only be conducted as a research project. Applications proposing clinical trials as part of a Scientific Core will not be reviewed.

Scientific Advisory Panel

Each IPCP-MBP awardee will be required to establish a Scientific Advisory Panel (SAP) no later than 6 months after award. The SAP will consist of 3 or more investigators not affiliated with any of the institutions comprising the IPCP-MBP, but who may be collaborators with IPCP-MBP investigators and have relevant expertise. Membership will be determined in consultation with the NIAID Project Scientist and the SAP scientific expertise and be relevant to the IPCP-MBP program. The SAP will attend the IPCP-MBP annual meetings to review program activities and evaluate progress, adherence to timelines, and the continued relevance of each project to the overall goals. The SAP will recommend new directions as appropriate and will provide upon request of the PD/PI and NIH Project Scientist a comprehensive written evaluation of the group’s activities and the Panel’s recommendations following the annual meeting. See Section VI. Award Administration Information.

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, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities.

Application Types Allowed

New

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

Funds Available and Anticipated Number of Awards

NIAID intends to commit $9.1 million yearly for 1 to 3 awards.

Award Budget

The IPCP-MBP Program application must consist minimally of 2 projects and an Administrative Core at a total direct base cost limit per year of $0.8 million (range $0.5 to $0.8 million). Applications may request additional funding per year to support research in any or all of the following areas of interest:

  • An additional $0.3 million (range $0.2 to $0.3 million) may be requested for applications using non-human primates and/or humanized mouse models for assessment of in vivo safety and/or efficacy of an nBP candidate or strategy.
  • Up to $0.6 million (range $0.2 to $0.6 million) may be requested for applications incorporating an exploratory pre-Phase I clinical trial(s).
  • Up to $0.3 million (range $0.2 to $0.3 million) may be requested for applications incorporating behavioral studies of nBP acceptability and/or adherence for use in either a standalone project or for incorporating these studies into a proposed pre-Phase I clinical trial(s).
  • Up to $0.2 million (range $0.1 to $0.2 million) per year for development and pilot clinical testing of quantitative biomedical methods to measure product adherence. 
  • Support for a total of 3 years during the 4 or 5 year duration of award may be requested for a single IND-enabling critical path project with a maximum direct cost per year of $0.8 million (range $0.4 to $0.8 million). The monies identified for support of this activity may not be used for these types of activities when they are incorporated into another project or core.

The total direct cost requested for the IPCP-MBP application (base plus combination of 1-4 above) must not exceed $3.0 million per year.

Award Project Period

An applicant may request a project period of up to 4 years for an application that does not include a pre-Phase I clinical trial, and up to 5 years for an application that includes a pre-Phase I clinical trial.

NIH grants policies as described in the NIH 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

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

Nonprofits Other Than Institutions of Higher Education

For-Profit Organizations

Governments

Other

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 must complete the following registrations as described in the SF424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

All Program Directors/Principal Investigators (PD(s)/PI(s)) and component Project Leads that are not yet registered in eRA Commons must work with their institutional officials to register. Also, institutional officials at the applicant organization should ensure that the eRA Commons account for the contact PD/PI is affiliated with their organization.

eRA Commons accounts are necessary to use ASSIST to prepare and submit applications.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least 6 weeks prior to the application due date.

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.

An investigator may not serve concurrently as the PD/PI for more than one IPCP-HTM or IPCP-MBP application or award at any time. However, a PD/PI may serve as a Project Leader and/or Scientific Core Leader on one or more applications provided the total effort does not exceed 12 person months and there is no scientific overlap.

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.

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

Section IV. Application and Submission Information


1. Requesting an Application Package

Applicants can access the SF424 (R&R) application package associated with this funding opportunity using the “Apply for Grant Electronically” button in this FOA or following the directions provided at Grants.gov.

Most applicants will use NIH’s ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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 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:

The letter of intent should be sent to:

Peter Jackson, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases (NIAID)
Room 3133, MSC-7616
6700B Rockledge Drive,
Bethesda, MD 20892-7616
Zip Code for express couriers: 20817-1821
Telephone: 301-496-8426
Email: pjackson@niaid.nih.gov

Page Limitations


Component Types Available in ASSIST

Research Strategy/Program Plan Page Limits

Overall

12 pages

Admin Core

6 pages

Core

6 pages

Project

12 pages


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

Instructions for the Submission of Multi-Component Applications

The following section supplements the instructions found in the SF 424 Application Guide, and should be used for preparing a multi-component application.

The application should consist of the following components:

Overall Component

When preparing your application in ASSIST, use Component Type ‘Overall’.

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

SF424 (R&R) Cover (Overall)

Complete entire form.

PHS 398 Cover Page Supplement  (Overall)

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Research & Related Other Project Information (Overall)

Follow standard instructions.

Facilities and Other Resources: Do not include a “Facilities & Other Resources” attachment in the Overall Component.  Instead, upload a separate attachment containing only the information relevant to each individual Research Project and Core within that component of the application.

Equipment: Do not include an “Equipment” attachment in the Overall Component.  Instead, upload separate attachments containing only the information relevant to each individual Research Project and Core within that component of the application.

Project/Performance Site Location(s) (Overall)

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Research & Related Senior/Key Person Profile (Overall)

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

Budget (Overall)

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover. Applicants may request a total direct base cost limit per year of $0.8 million (range $0.5 to $0.8 million), but may not exceed a total direct cost of $3.0 million per year.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

PHS 398 Research Plan (Overall)

Introduction to Application: Not Applicable

Specific Aims: List in priority order, the broad, long-range objectives and goals of the proposed Program. Concisely and realistically describe the hypothesis or hypotheses to be tested.

Research Strategy: This narrative section summarizes the overall research plan for the multi-component application. The multi-component application should be viewed as a confederation of interrelated research projects, each capable of standing on its own scientific merit, but complementary to one another. This is an important section for it provides the group of investigators an opportunity to give conceptual wholeness to the overall program – by giving a statement of the general problem area and by laying out a broad strategy for attacking the problems including how the program as a whole incorporates integrated and iterative research and development projects and cores that facilitate advancement of nBP. As the strategy develops, each project and core should be cited briefly as to its place in the overall scheme. Summarize the special features in the environment and/or resources that make this application strong or unique. Applicants should describe the private sector involvement and expertise, activities, other resources and processes that would not otherwise be available to the investigators and how the private sector (industrial) component is integrated into the proposed IPCP-MBP Program. The overarching objectives and specific aims of the IPCP-MBP application need to be discussed in the context of the proposed milestones, Go/ No-Go decision points and Gantt charts/timelines that will guide the IPCP-MBP research plan. If a TPP is proposed for the nBP product then the objectives, specific aims and milestones need to support the development of the nBP product or strategy described in the TPP.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modification:

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.

Administrative Core

When preparing your application in ASSIST, use Component Type ‘Admin Core.’

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

SF424 (R&R) Cover (Administrative Core)

Complete only the following fields:

PHS 398 Cover Page Supplement (Administrative Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Administrative Core)

Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

Project Narrative:  Do not complete.

Project /Performance Site Location(s) (Administrative Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Administrative Core)

Budget (Administrative Core)

Budget forms appropriate for the specific component will be included in the application package.

Funding for the overall administrative efforts should include secretarial, and/or other administrative services, expenses for publications demonstrating collaborative efforts, and communication expenses. Travel funds for the PD(s)/PI(s), Project Leaders, Scientific Core Leaders, other key IPCP-MBP personnel, and SAP members to attend an annual IPCP-MBP meeting should be included.

Applicants proposing pre-Phase I clinical trials where travel is required to coordinate activities among clinical sites, may request additional travel funds for clinical trial site oversight within the Administrative Core, if a regulatory core is not requested. If a regulatory core is requested then the travel budget should reside in that core. All such travel requests should be well justified.

No travel funds may be requested for attendance of scientific meetings.

PD(s)/PI(s), Project Leaders, and Administrative and Scientific Core Leaders are requested to commit substantial time and effort to ensure success of the complex IPCP-MBP program. It is recommended that these individuals devote a minimum of 2.4 person months per year to the Program. This level of commitment can be all in one project/core or a total effort across several projects/cores within a single application. If effort is devoted to multiple cores and/or individual research projects, the level of effort is expected to be commensurate with the direct involvement necessary to ensure successful implementation and management of each project and/or core.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan   (Administrative Core)

Specific Aims:  List in priority order the broad, long-range objectives and goals of the proposed core. In addition, state the core’s relationship to the goals and how it relates to the individual research projects or other cores in the application.

Research Strategy: The applicant should include a plan addressing the short- and long-term management of the program. The Administrative Core Research Strategy must specifically address communications, group meetings, website development, teleconferences, scientific meeting presentations and publication of data, program internal sharing of information and shipping and control of reagents. Applicants should include plans to track progress and outcomes within the IPCP-MBP program. Procedures for addressing delays in meeting Go/No-Go decision points, milestones, starting animal and/or clinical studies should be provided. Include a plan describing management and oversight of the TPP, if used. Plans for leadership succession, and dispute resolution should be included. The management and operations of the Scientific Advisory Panel (SAP) should be outlined. This section must include a discussion of the role of the SAP and its integration into the operations of the IPCP-MBP. Applicants should describe procedures and approaches for obtaining SAP and NIAID input via teleconferences, ad hoc and annual meetings, review of written materials/data, etc. Applicants should describe the expertise categories to be represented on the SAP, and how the SAP will be utilized to guide the IPCP-MBP program. If clinical research or a clinical trial is proposed in the application the SAP should include relevant clinical trial experience.

NOTE: Applicants MUST NOT name proposed SAP members in their applications or contact potential SAP members prior to application submission and completion of peer review.

The day–to–day management of the IPCP-MBP award will be overseen by a steering committee.  Describe the frequency of teleconferences and how they will be managed. Describe how the steering committee will be used to oversee progress of the IPCP-MBP award and monitor and administer the policies and procedures created by the Administrative Core.

Milestones: Describe the Administrative Core milestones. Narratives should identify the administrative goals by providing description for quantifiable measures of success within a specific time interval, and be incorporated into Gantt charts and selection algorithms with specific Go/No-Go criteria for use in guiding IPCP-MBP management decisions. In addition to providing quantifiable measurements for administrative outcomes, applicants should also describe how milestones will be used by the IPCP-MBP team and SAP to track successes and failures. Milestones should not be a restatement of application Administrative Core specific aims. The best constructed milestones will be a concise summary/outline of the quantitative specifications for identification of a successful Administrative Core effort.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modification:

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.

Research Projects

When preparing your application in ASSIST, use Component Type ‘Project.’

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

SF424 (R&R) Cover (Project Name)

Complete only the following fields:

PHS 398 Cover Page Supplement (Research Projects)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Projects)

Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

Project Narrative:  Do not complete.

Equipment: For each individual Research Project, include an “Equipment” attachment that provides information on resources available for that project.

Project /Performance Site Location(s) (Research Projects)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Research Projects)

International shipping of research reagents and biohazardous material;

Conducting facility audits;

Providing oversight of GLP and GMP activities;

Regulatory requirements.

Budget (Research Projects)

Budget forms appropriate for the specific component will be included in the application package.

Each individual Research Project component should have a separate budget that details the costs required to support that Research Project.

Applicants may request a total direct base cost limit per year of $0.8 million (range $0.5 to $0.8 million), and may add additional elements to proposed projects or create a project from the areas below (below), but must not exceed a total request of $3.0 million in direct costs per year:

Support for a total of 3 years during the 4 or 5 year duration of award may be requested for a single IND-enabling critical path project per application with a maximum direct cost per year of $0.8 million (range $0.4 to $0.8 million). The monies identified for support of this activity should not be used for these types of activities when they are incorporated into another project or core.

Projects containing pre-Phase I clinical trials can request budgets prior to initiation of study enrollment and as early as year 1 of the award. These funds should be used to support protocol development, meeting DAIDS clinical trial requirements and regulatory requirements.

Budgets to support research at foreign sites (non-U.S.) should not be requested for creation of new infrastructure, and no more than 15% of a requested foreign site budget should be used for personnel training.

Requests for additional travel to visit subcontractor or consortium sites for discussion and planning involved in supplying specific assays or services, such as GLP/GMP services in support of an IND-enabling critical path project or animal testing must be specifically justified. In the case of travel for facility audits and oversight of GLP and GMP activities, applicants should provide not only justification for the travel, but also assurances that the personnel traveling are qualified to conduct the audit and provide oversight.

No travel funds may be requested for attendance of scientific meetings.

PD(s)/PI(s), Project Leaders, and Administrative and Scientific Core Leaders are requested to commit substantial time and effort to ensure success of the complex IPCP-MBP program. It is recommended that these individuals devote a minimum of 2.4 person months per year effort to the Program. This level of commitment can be all in one project/core or a total effort across several projects/cores within a single application. If effort is devoted to multiple cores and/or individual research projects, the level of effort is expected to be commensurate with the direct involvement necessary to ensure successful implementation and management of each project and/or core.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Research Projects)

Specific Aims: List, in priority order, the Specific Aims of the proposed project. Concisely and realistically describe the hypothesis or hypotheses to be tested. In addition, state the individual Research Project’s relationship to the Program goals and how they relate to other Research Projects or Cores in the application.

Research Strategy: Use this section to describe how the proposed research will contribute to meeting the IPCP-MBPs goals and objectives and explain the rationale for selecting the methods to accomplish the specific aims. In addition to stating the biological significance of the research, indicate the project's relevance to the primary theme of the application. Experimental details should be cited using the “Bibliography and References Cited” attachment and need not be detailed in the Research Strategy. Describe the research design, conceptual procedures, and analyses to be used to accomplish the Specific Aims of the project. Describe any new methodology and its advantage over existing methodologies. Describe any novel concepts, approaches, tools, or technologies for the proposed studies. Discuss associations with clinical project(s). Discuss the potential difficulties and limitations of the proposed procedures and alternative approaches to achieve the aims.

Letters of Support: Applicants should include letters outlining arrangements with foreign authorities made to allow the export of tissues, secretions and biological materials from collaborative sites outside of the continental U.S. for analysis in the U.S. 

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modification:

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.

Scientific Core(s)

When preparing your application in ASSIST, use Component Type ‘Core.’

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

SF424 (R&R) Cover (Scientific Core(s))

Complete only the following fields:

PHS 398 Cover Page Supplement (Scientific Core(s))

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Scientific Core(s))

Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

Project Narrative:  Do not complete.

Facilities & Other Resources: For each individual Core, include a “Facilities & Other Resources” attachment that provides information on resources available for that Core. If there are multiple performance sites, describe the resources available at each site. Describe any special facilities used for working with biohazards or other potentially dangerous substances. Include a description of how the scientific environment in which the core service or resource will be conducted contributes to the probability of success (e.g., institutional support, physical resources, and intellectual rapport).

Equipment: For each individual Core, include an “Equipment” attachment that provides information on resources available for that Core.

Project /Performance Site Location(s) (Scientific Core(s))

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Scientific Core(s))

Budget (Scientific Core(s))

Budget forms appropriate for the specific component will be included in the application package.

Each individual Core Component should have a separate budget that details the costs required to support that Core.

Budget must describe apportionment of dollars or percentage of dollars within the Scientific Core that will be required to support each component research project.

Requests for additional travel to visit subcontractor or consortium sites for discussion and planning involved in supplying specific assays or services, such as GLP/GMP services in support of an IND-enabling critical path project or animal testing must be specifically justified. In the case of travel for facility audits and oversight of GLP and GMP activities, applicants should provide not only justification for the travel, but also assurances that the personnel traveling are qualified to conduct the audit and provide oversight.

Applicants proposing pre-Phase I clinical trials where travel is required to coordinate activities among clinical sites, may request additional travel funds for clinical trial site oversight within a regulatory core. If a regulatory core is requested then this funding should reside in this core.

No additional travel funds may be requested for attendance of scientific meetings

PD(s)/PI(s), Project Leaders, and Administrative and Scientific Core Leaders are requested to commit substantial time and effort to ensure success of the complex IPCP-MBP program. It is recommended that these individuals devote a minimum of 2.4 person months per year effort to the Program. This level of commitment can be all in one project/ core or a total effort across several projects/ cores within a single application. If effort is devoted to multiple scientific cores and/or individual research projects, the level of effort is expected to be commensurate with the direct involvement necessary to ensure successful implementation and management of each project and/or core.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan  (Scientific Core(s))

Specific Aims: List in priority order the broad, long-range objectives and goals of the proposed core. Concisely and realistically describe the hypothesis or hypotheses to be tested. In addition, state the core’s relationship to the goals and how it relates to the individual research projects or other cores in the application.

Research Strategy: Use this section to describe how the proposed Core activities will contribute to meeting the Programs goals and objectives and explain the rationale for selecting the general methods and approaches proposed to accomplish the Specific Aims. In addition, this section should indicate the relevance of the Core to the primary theme of the application. The application must indicate the specific projects to be served by the Scientific Core(s). The activities of Scientific Cores must not overlap with those of a proposed project. Scientific Cores should provide broad-based support for routine activities that individual projects may need to facilitate their development activities.

Experimental details should be cited using the “Bibliography and References Cited” attachment and need not be detailed in the Research Strategy. 

Applicants must provide Scientific Core specific well-described, quantifiable, and scientifically justified milestones that are not simply a restatement of specific aims for the overall application. Milestones should be presented via a Gantt chart or equivalent, with associated timelines and identified outcomes. Milestones must specify the outcome(s) for each activity. For milestones associated with more basic science-oriented cores applicants should describe specific criteria, benchmarks or outcomes to be met that can be used to quantify progress. All proposed milestones should be integrated with the overall goals of the proposed IPCP-MBP Program. Applicants should describe plans for periodically revisiting and revising milestones and timelines, if needed, as new information becomes available, challenges to the proposed development path are encountered, and research outside the IPCP-MBP modifies the science of nBP. Milestones and timelines should be placed at the end of the Research Strategy section for each Scientific Core component and fall within the page limits.

If a Regulatory Core is included in the IPCP-MBP, applicants should describe its role in meeting NIAID/DAIDS administrative and FDA requirements for conducting clinical trials. How Regulatory Core guidance will be communicated and implemented by the IPCP-MBP team, as well as its processes for developing guidance should be described

Scientific Core(s) which include or are derived solely from an Industry partner must address the resources and expertise that the industrial partner brings to the IPCP-MBP. Descriptions should include how the partners’ expertise will be integrated into and what value it will bring to the overall objectives and operations of other projects and cores in the IPCP-MBP, and the IPCP-MBP as a whole.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modification:

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.

Foreign Institutions

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

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. 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) using ASSIST or other electronic submission systems. 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.

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.

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. 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.

6. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

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.

Important reminders:
All PD(s)/PI(s) and component Project Leads 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.

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 (SAM). 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 by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete 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-10-115.

Section V. Application Review Information


1. Criteria

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Overall Impact - Overall

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the Program 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 Program proposed).

Do the Program Director(s)/Principal Investigator(s) have the leadership and scientific ability to develop an integrated and focused research program?

Will the Program Director(s)/Principal Investigator(s) devote adequate time and effort to the program?

Has innovation been established in the context of the global need for an nBP to prevent HIV acquisition/transmission?

Is the innovation of the IPCP-MBP Program realized through iterative development and advancement of the NBP candidate or strategy, where the value added to the field is achieved through the interactions of the individual projects and cores?

Does the integration of the overall program establish an iterative approach to the developmental problem(s) of creating an nBP candidate or strategy?

Are the multi-disciplinary scope of the program and the coordination and interrelationships for all individual research projects and Scientific Core(s) appropriate and focused on the common theme?

Is the private sector component well integrated and positioned to contribute significantly to the proposed IPCP-MBP Program?

Overall Impact - Individual Research Projects

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 - Individual Research Projects

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? 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? What is the potential biomedical significance of the proposed project and will it advance the nBP field by providing new technologies, single or combination nBP candidates or strategies? For applications proposing pre-Phase I clinical trial projects, have the applicants provided sufficient information to describe the proposed trial and demonstrate that it has the potential to advance the field of nBP?

Investigator(s)

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? Are the time commitments of the Project Leaders appropriate?

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?   

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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? 

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed? Is the pre-Phase 1 clinical trial(s) appropriately designed to control subject risk, and if iterative pre-Phase I clinical trials are proposed, how do the outcomes relate to the objectives of the project, and to the overall program? Are there a sound scientific rationale and basis for the nBP candidate and/or strategy, and does the strength of the existing data support product feasibility, safety and potential efficacy? Is there a sound scientific rationale and basis for the development of any proposed new nBP-associated technology or model? Is the proposed project appropriate for the stage of development of the candidate nBP?

Is the IND-enabling clinical path project adequately described and does it incorporate appropriate oversight of GMP and GLP activities? Are the proposed outcomes of the IND-enabling clinical path project adequately justified and timed in terms of the information it may supply to other projects and cores?

Does the proposed private sector (industry) involvement provide access to expertise, activities, other resources and processes that would not otherwise be available to the investigators?

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?

Overall Impact – Individual Cores

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the core 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 core proposed).

Review Criteria – Individual Cores

Reviewers will consider each of the review criteria below, as appropriate for the individual core, in the determination of scientific merit and provide an overall impact score for each Core, but will not give separate scores for these items.

Administrative Core

Is the administrative and organizational structure appropriate to facilitate attainment of the objective(s) of the proposed IPCP-MBP? Are the experience, level of commitment, and established competence in organizing multi-project and cores demonstrated, and availability of the Administrative Core Leader and administrative staff adequate to manage the IPCP-MBP program? Are the operational activities of the Administrative Core appropriately justified as supporting the research projects and cores? Are the plans for coordination, problem identification and resolution, and the organizational structure proposed appropriate and adequate to the attainment of the objective(s) of the proposed program?  Does the management plan provide for ongoing formal and informal communications within the IPCP-MBP? Has an administrative structure been proposed that allows for decisions to be made in the absence of the IPCP-MBP Program leaders or to replace him/her if the need arises? Are the proposed plans to manage subcontracts and fee-for-service activities adequate to assess the quality/appropriateness of the facilities, methods and other resources to be used? 

Scientific Cores

Is provision of resources and core services for the individual Research Projects critical and justified? Is the relationship of a Scientific Core to the central focus of the overall program strong? Is the quality of the relevant facilities or services provided and criteria for prioritization and usage appropriate? Are the qualifications, competence, and commitment of the Core Leader and key personnel appropriate? Are the core facilities appropriate and adequate to support at least two of the individual research projects? Is the relationship of each core to the central focus of the overall IPCP-MBP established and well justified? Are the criteria for prioritization and usage of core facilities or services (including procedures, techniques, and quality control) appropriate?

Additional Review Criteria - Overall, Research Projects, and Cores

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.

Milestones

Given the critical nature of the milestones to measure the success of the IPCP-MBP program and nBP development, are the proposed milestones well-defined with quantifiable measures that are appropriate for assessing the success? Are the milestones appropriate, adequately described, feasible, quantifiable and achievable within the proposed time frame for the elements they support? Do the milestones incorporate Go/No-Go criteria appropriate for the described testing?  Are the Milestones well-integrated into Gantt charts and achievement measured using Go/ No-Go decision criteria? And if there is a proposed TPP for the nBP do the proposed milestones lead to the desired product properties identified in the TPP? Is it clear how the IPCP-MBP Program and its scientific and operational objectives will evolve as milestones are achieved? Given the potential benefits of the proposed research, do the milestones support the potential for the overall program to advance the proposed nBP strategy? Are the individual projects, Scientific Cores(s) and Administrative Core milestones appropriate for their proposed efforts, feasible within the proposed timeframes, and integrated with the overall milestones for the IPCP-MBP program?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six 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 six 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 Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children 

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. 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 - Overall, Research Projects, and Cores

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) Genome Wide Association Studies (GWAS).

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 NIAID, 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:

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:

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

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 the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

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.

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 (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH 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 NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH 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 the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

Areas of Joint Responsibility include:

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Reporting

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590 or RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, 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. 

Section VII. Agency Contacts

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

Application Submission Contacts

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading or navigating forms)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-435-0714
TTY 301-451-5936
Email: GrantsInfo@nih.gov

eRA Commons Help Desk (Questions regarding eRA Commons registration, tracking application status, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov

Scientific/Research Contact(s)

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

Peer Review Contact(s)

Peter Jackson, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-496-8426
Email: pjackson@niaid.nih.gov

Financial/Grants Management Contact(s)

Mollie Shea
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-402-6576
Email: mshea@niaid.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 Parts 74 and 92.


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