Part 1. Overview Information

Key Dates

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts ).

Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to provide an immunologic reagent resource that will support and advance the optimal use of nonhuman primate (NHP) models for vaccine and adjuvant development, transplantation, and infectious and immune-mediated diseases. A specialized resource is required because many immune-monitoring, -depleting, and -modulating reagents developed for mouse or human research, or those approved for clinical use, are either suboptimal or nonfunctional with NHP cells or proteins or are not available for use in NHP research. The NHP Reagent Resource (hereafter referred to as “the Resource”) will identify, obtain, develop, characterize, produce, evaluate, and distribute to the scientific community key immunologic reagents for NHP research that are not commercially available or, if available, are not optimized for use in NHP research. Reagent categories include: 1) in vitro use diagnostics to monitor or characterize immune responses; 2) in vivo detection or imaging of immunologic cell surface, intracellular, or soluble molecules; and 3) in vivo immune-modulation and immune-based therapeutics. Examples include monoclonal antibodies (mAbs), soluble receptors/ligands, chimeric/recombinant proteins or mAbs, virus stocks for transforming NHP cell lines, and other novel, state-of-the-art immunologic reagents.

In addition to the development, production, and distribution of new reagents, the Resource will produce, maintain, and distribute existing reagents offered under the current NIAID NHP Reagent Resource. The Resource will engage with the scientific community and NIAID to identify and prioritize new reagents for development and to assess the continuing need for existing reagents. The Resource will also develop, provide, curate, and maintain a public website and provide, or contribute and link to, a searchable database of information about commercially available immunologic reagents developed for human, mouse or other species that cross-react with NHP cells or proteins. The website will provide relevant information, technical specifications, and protocols for use of reagents provided by the Resource. This FOA is for the continued support of all activities of the Resource supported by NIAID. A central goal of this FOA is the development of reagents, with commercialization rights, that will remain accessible to the NHP research community.

Background

NIAID supports basic, translational, and clinical research to define immunological responses and mechanisms, as well as application of these findings to the development of effective vaccine, prevention, and therapeutic strategies for infectious and immune-mediated diseases. The use of NHPs for translational research is a critical component of NIAID’s efforts to translate basic discovery research to clinical practice. NHP species are the preferred model for most late-stage preclinical research because they approximate human physiology, immunology, and genetics more closely than any other model. In addition, NHP research models often provide compelling data and/or are required for Federal Food and Drug Administration (FDA) Investigational New Drug (IND) approval prior to the initiation of clinical trials of new therapeutics or vaccines. Commonly used NHP species in immune and infectious disease research, and the primary, albeit not exclusive, focus of this FOA, are the:

• cynomolgus macaque (Macaca fascicularis),
• rhesus macaque (Macaca mulatta),
• baboon (multiple Papio species),
• pigtail macaque (Macaca nemestrina).

These species are central to many aspects of translational biomedical research including: 1) development of candidate vaccines against human pathogens, including HIV and emerging infectious diseases, and evaluation of their safety and efficacy; 2) development and evaluation of new strategies to prolong survival of and/or induce immune tolerance to organ, cellular, and composite tissue transplants; and 3) studies of disease pathogenesis and evaluation of novel immune-based therapies for infectious and immune-mediated diseases. Use of the NHP model has led to many immunologic and infectious disease research advances, most notably in AIDS pathogenesis, treatment, and vaccine development. A specialized resource is needed because many immune-monitoring, -depleting, and -modulating reagents developed for mouse or human research or clinical use are either nonfunctional, suboptimal, or not available for use in NHP research. The research tools generated and provided through this initiative will significantly enhance reproducibility, rigor, and the optimal use of these critical research models, thereby accelerating research targeted at developing cures, vaccines, and treatments for immune-mediated diseases, as well as emerging and reemerging infectious diseases.

To address the critical scarcity of in vitro and in vivo immunologic reagents for NHP models research, the NIAID initiated support of the Resource in FY 2004 through a competitive contract solicitation and continued support through a competitive renewal in FY 2009. In FY 2016 the Resource was competitively renewed as a cooperative agreement (U24). The Resource offers over 100 unique reagents to researchers worldwide, filling approximately 500-600 requests representing over 1 kilogram of protein annually.

Research Objectives and Scope

This objective of this FOA is for the continued support of all activities of the Resource supported by NIAID. A central goal of this FOA is the development of reagents, with commercialization rights, that will remain accessible to the NHP research community. The objectives and scope of the Resource activities fall into two broad categories: 1) development, acquisition, production, and distribution of reagents; and 2) website and management activities. Applicants are required to address both categories in the application.

Reagent Development, Reagent Acquisition, Reagent Production, and Reagent Distribution

The responsibilities of the Program Director/Principal Investigator (PD(s)/PI(s)) include all aspects of the production and distribution of the approximately 100 existing reagents developed under NIAID contract and grant support and currently offered by the Resource. The Resource will provide protocols, procedures, records for, and inventories of, reagents developed under the previous contracts and grant to the new awardee at the time of award.

This FOA will also support the development of new reagents as well as outreach efforts to the scientific community to identify evolving immunologic reagent needs.

• Examples of reagent categories include, but are not limited to: mAbs, soluble receptors/ligands, chimeric/recombinant proteins or mAbs, virus stocks for transforming NHP immune cell lines, and other novel state-of-the-art immunologic reagents.
• Examples of applications for reagents to be developed include, but are not limited to: 1) in vitro use diagnostics to monitor and/or characterize immune responses; 2) in vivo detection or imaging of immunologic cell surface, intracellular, or soluble molecules; and 3) in vivo immune-modulation and immune-based therapeutics;

Applicants are required to propose at least two new (candidate) immunologic reagents potentially needed for NHP research, each to a unique target or a unique specificity, one for in vitro use and one for in vivo use, that are not commercially available, or if available, are not optimally formulated for NHP use and are not already provided by the Resource. The candidate reagents may be currently in an early stage of development, or in consideration for development. One of the two candidate reagents should be for (a) in vitro detection or imaging of a cell surface, intracellular, or soluble molecule; and the other for (b) in vivo immune-modulation (e.g. blocking, agonist, or antagonist), including potential immune-based therapeutics.

The development of new reagents includes all technologies required for state-of-the-art reagents (e.g., cloning and sequencing the gene of interest; generating a new mAb by various methods and screening for specific characteristics; genetic engineering of a newly generated or existing mAb or protein; and using adduct technologies for labeling proteins and antibodies). In addition, the PD(s)/PI(s) will be responsible for characterization, formulation, evaluation, and validation of the specificity, reproducibility, stability, activity, and unique characteristics of both in vivo and in vitro use reagents prior to larger production runs, as applicable.

Production and purification of reagents will require a range of small- to large-scale production runs (approximate range of 1 gram/1 liter to 300 grams/250 liters). Note that reagents produced are not required to be cGMP. However, reagents for in vivo use must be highly purified and produced and formulated as reagents that are safe and appropriate for use in NHPs. In addition, in vivo use reagents should meet IACUC requirements for use in animals.

The Resource will include quality control and assurance procedures for each product line and provide optimized protocols for the use, storage, and shipment of reagents, both domestically and internationally. The timely distribution of reagents to the NHP research community will require maintenance of sufficient inventories of frequently used reagents.

Website and Management Activities

The Resource will develop and provide a public website to disseminate information about Resource activities and provide, or contribute and link to, a searchable database of commercial and non-commercial antibodies/immunologic reagents developed for humans, mice or other species that cross-react with NHP cells or proteins. At a minimum, the public website will provide background information, registration information for ordering reagents, reagents available, technical specifications, protocols, and online user feedback and recommendations for new reagents.

The Resource will inform the scientific community about its activities and promote use of the Resource on an ongoing basis. Examples of community engagement include presentations at scientific conferences and direct outreach to investigators working in NHP models. The PD(s)/PI(s) will be responsible for implementation and maintenance of state-of-the-art data management systems, including electronic production records, inventory and order tracking, and secure handling of sensitive information.

Overall Management Plan

PD(s)/PI(s) will be responsible for management and oversight of Resource activities including, but not limited to, subcontracts, material transfer and licensing agreements, secure webhosting, and recovery of production costs of in vivo use reagents.

Note: This FOA will not support the following activities or reagents. Applications that include research proposed in these areas below will be considered non-responsive and will not be reviewed:

• Applications that do not propose development of at least two new (candidate) immunologic reagents potentially needed for NHP research, each to a unique target or a unique specificity, one for in vitro use and one for in vivo use, that are not commercially available, or if available, are not optimally formulated for NHP use
• Development or provision of antibodies, therapeutics, or reagents to infectious disease agents or reagents for non-immunologic use (e.g., antibodies or other reagents to viruses or viral proteins or viral components, antibodies or recombinant proteins specifically designed to block entry of viruses into NHP immune cells, or microbial recombinant proteins); however, development and/or provision of such reagents may be allowed after award at the discretion of the NIAID Program Official under highly exceptional circumstances, e.g., public health emergencies
• Immunologic reagents not suitable for use in NHP research
• Viral stocks, unless used for generating immune reagents or for immune assays (e.g., NHP-specific transforming viruses for generating immortalized antibody producing plasma cells are within the scope of the FOA)
• Reagents for animal model research other than NHP species
• Reagents for clinical trials or clinical research
• Clinical trials or clinical research

Note: Applications that do not include an Overall Management Plan will be considered incomplete and will not be reviewed.

For any questions concerning the scope of this FOA, applicants are encouraged to contact the Scientific/Research Contact.

Annual Meetings

The PD(s)/PI(s) will participate in an annual face-to-face meeting with the NIAID Program Official and other NIAID Program Officers to update these personnel on the status of the Resource. The meeting may include external scientific advisors as determined by NIAID. Additional key personnel and other relevant staff may attend when appropriate. In addition, each year the PD/PI or up to 2 PDs/PIs, if multiple PD(s)/PI(s), will also attend one NIAID scientific or consortium meeting, determined by the NIAID Program Official, to update attendees about the Resource and to solicit recommendations for new reagent needs.

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Governments

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed. 

Applicant organizations

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

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

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

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

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

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

2. Cost Sharing

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

3. Additional Information on Eligibility

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

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

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101)

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

Letter of Intent

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

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

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

The letter of intent should be sent to:

Tara Capece, Ph.D., MPH
Telephone: 301-761-7854
Email: [email protected]

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

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

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

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

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

, with the following additional instructions:

Equipment: Include a description of the equipment available for large-scale production (range of 100 – 250 liters/run) and purification (range of 75 – 300 grams/run) of monoclonal antibodies, and for storage of at least 12 months inventory of all reagents (see budget assumptions, below).

Other Attachments: Provide an Overall Management Plan for the Resource as a PDF attachment, with the filename of "Management_Plan.pdf". Applications lacking this Overall Management Plan will be deemed incomplete and will not be reviewed. The Overall Management Plan should include plans for:

• Management and oversight of subcontracts and any fee-for-service activities.
• Timely processing of materials transfer and licensing agreements. Include plans for the management of Materials Transfer Agreements and Intellectual Property Rights for reagents developed under the Resource consistent with the goals of this FOA to develop reagents, with commercialization rights, such that they remain readily accessible to the NHP research community.
• Secure webhosting with credit card processing capabilities for order tracking and recovery of production costs for in vivo use reagents.
• Succession of leadership in the event it is necessary.
• Lines of authority and responsibilities of personnel.
• The timely transition of these resources to a future awardee or other NIAID-designated resource at the end of this award.

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

, with the following additional instructions:

In the biosketches discuss the PD(s)/PI(s) scientific, technical, and managerial expertise and experience in planning, managing, and directing projects of similar scope, complexity, and size as those required for this Resource. In addition, discuss the PD(s)/PI(s) experience in relevant community outreach and identification of research reagent needs.

R&R Budget  

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

, with the following additional instructions:

Each PD(s)/PI(s) must commit a minimum of 5 person months per year.

Applicants should budget annually for the following:

a. Annual replenishment of existing reagents to maintain inventories. Include costs for the purification, formulation, vialing, characterization, evaluation, quality control and quality assurance related activities for each. Include production costs for in vitro use reagents. Do not include actual production costs for in vivo use reagents, which will be recovered from requesting investigators. Budgets should be commensurate with approximations of recent annual activities performed by the Resource.

b. Annual requests and shipments of existing reagents. Budgets should be commensurate with approximations of recent annual activities performed by the Resource.

c. Annual development, production, and evaluation of new reagents:

• include all development, genetic engineering/modification, production for evaluation, and evaluation costs for both in vitro and in vivo new reagents based on annual anticipated demand/need. For development and engineering include all aspects as required. Specify the gram and liter production quantities required for evaluation. Budget for in vivo evaluation of at least two newly developed in vivo reagents per year but do not include the purchase cost for nonhuman primates used in evaluation studies. NIAID will provide animals at no cost;
• Budgets should be commensurate with the current development pipeline for new reagents.

d. Other annual costs:

• costs associated with data management and website development and maintenance;
• outreach costs to promote the Resource to new users and to identify reagents needed by the NHP research community;
• travel for up to 2 PD(s)/PI(s) to attend an annual meeting with NIAID and an annual NIAID scientific consortium meeting, both held over 1.5 days in Rockville, MD; and,
• travel to 2 domestic scientific meetings a year, or for 2 staff to attend 1 domestic scientific meeting per year.

Do not budget for:

• shipments of reagents (investigators requesting reagents will pay for shipping costs) and
• production and purification costs for in vivo use reagents, typically gram quantities (requesting investigators will pay for production/purification costs). Note: production/purification does not include development, characterization, evaluation, quality control, or quality assurance.

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

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

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

Specific Aims: List the specific aims of the proposed program and describe the resources that will be provided to the research community.

Research Strategy: Propose detailed plans and timelines for each of the following activities/areas. Include supporting data from similar work or relevant experience. The format may be adjusted to best reflect the aims and proposed work. Discuss how the proposed project will support the advancement of NHP immunology research, facilitate optimal use of the models for vaccine and adjuvant development, transplantation, and infectious and immune-mediated diseases.

Reagent Development, Acquisition, Production, and Distribution

• Propose at least two new (candidate) immunologic reagents potentially needed for NHP research, each to a unique target or a unique specificity, one for in vitro use and one for in vivo use, that are not commercially available, or if available, are not optimally formulated for NHP use and are not already provided by the Resource. The candidate reagents may be currently in an early stage of development, or in consideration for development. Note: the following are not considered a unique target or specificity: a reagent that is already available for a different NHP species than the species proposed, or a new label/tag or other immune-imaging or -detection modification to an already available reagent. Discuss how the candidate reagents will improve upon the development of immunological reagents by utilizing novel theoretical concepts, approaches, methodologies, or instrumentation. Discuss how the strategies proposed are limited to a single reagent application or specificity or applicable in a broader sense.

• One of the two candidate reagents should be for: (a) in vitro detection or imaging of a cell surface, intracellular, or soluble molecule; and the other for (b) in vivo immune-modulation (e.g., blocking, agonist, or antagonist), including potential immune-therapeutics. Examples of reagent categories for the two proposed candidate reagents include, but are not limited to, mAbs, soluble receptors/ligands, and chimeric/recombinant proteins or mAbs.

• Justify each candidate reagent in the context of a compelling need and its potential impact on NHP immunologic research.

• Describe all aspects of development and production approaches and methods for the two candidate reagents. Plan final production runs in the range of 75 milligrams and 100 grams for in vitro and in vivo use reagents, respectively. Include supporting data from similar work or relevant experience as appropriate. Also include the team's experience with and/or data using other approaches relevant to future reagent development or applications, in particular, novel or technically challenging strategies or approaches. Discuss feasibility, potential problems, and alternative strategies. Address anticipated timelines and benchmarks of success for the primary tasks and overall development and production stages below. Procedures/processes that are the same or highly similar for the two reagent categories may be presented as a single plan. Address each of the following in the development and production plans, as appropriate:

• Describe all stages of development; including technologies used and relevant experience (e.g., cloning the gene of interest, generating a new mAb hybridoma, screening for specific characteristics, genetically modifying a newly generated or existing mAb, and/or using adduct technologies for tagging proteins/antibodies).

• Propose/discuss plans for, and experience in, characterization, evaluation, and validation of the specificity, reproducibility, stability, activity, and unique characteristics of the reagent, as applicable.

• Propose/discuss plans for, and experience in, optimizing production, purification, formulation, storage, vialing, and labeling.

• Propose/discuss plans for, and experience in, establishing and implementing quality control and assurance procedures for each product line as well as overarching plans that will apply to all manufactured and distributed reagents (e.g., quality control and assurance, shelf life determination, purity assessment and standards, bioburden determinations and limits, release criteria, and other key criteria identified by the applicant). Address approaches to ensure reagents intended for in vivo use will be safe and appropriate for NHPs and meet IACUC requirements for use in animals.

• Propose/discuss plans for, and experience in, development of optimized protocols for the use, storage, and shipment of the two reagent categories.

Website and Management Activities Plan

• Current Resource reagents: Propose an overall plan for the continued timely provision/distribution of the approximately 100 existing reagents currently offered by the Resource to the NHP research community, including maintenance of reagent stocks and capacity to respond to unpredicted surges in demand. Provide details of relevant experience of the team.

• Outreach: Propose plans for outreach to the NHP research community, including publicizing the Resource’s capabilities and available services. Discuss strategies to identify the research community’s reagent needs.

• Data Management: Propose plans for an electronic data management system, including establishment and maintenance of detailed development and production records, technical data sheets, tracking systems for requests and orders, and any plans for secure off-site or cloud-based data storage. Provide details of relevant experience of the team.

• Website: Describe plans for website development, procedures to update the website information, and key features, that allow for secure user registration, feedback, new reagent requests, and orders. Discuss plans to provide or contribute and link to a regularly updated searchable database of commercial and non-commercial antibodies/reagents that react with specific NHP species. Provide details of relevant experience of the team.

Letters of Support: Provide a letter of support stating that the grantee institution will work with the current grantee institution and any future grantee institution, if applicable, to ensure that all required Material Transfer Agreements will be negotiated in a timely manner, and that an orderly transition of activities and resources to the grantee institution will be completed within three months of award.

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

The following modifications also apply:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan
• All applications should include plans for sharing with the scientific research community all reagents, assays, methodologies, and protocols developed with Resource funding, as appropriate and consistent with achieving the goals of the program.

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

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

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

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

4. Submission Dates and Times

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

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

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

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

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).

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 proposed Resource address the needs of the NHP research community that it will serve? Is the scope of activities proposed for the Resource appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research and/or change the concepts, methods, technologies, treatments, or preventative interventions that drive this field? Are prior research and experience that serve as the key support for the proposed project rigorous? How will scientific knowledge, technical capability, and/or clinical practice be improved?

Specific to this FOA: Does the application support the advancement of NHP immunology research and facilitate optimal use of the models for vaccine and adjuvant development, transplantation and infectious and immune-mediated diseases?

Investigator(s)  

Are the PD(s)/PI(s), collaborators, and other researchers well suited to their specific roles in the Resource? Do they have appropriate experience and training? Have they demonstrated experience and an ongoing record of accomplishments in managing immune reagent development research or similar work? Do the investigators demonstrate significant experience in coordinating collaborative basic research? If the Resource is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; are their leadership approach, plan for conflict resolution, and organizational structure appropriate for the Resource? Does the applicant have experience overseeing selection and management of subawards, if needed?

Innovation  

Does the application challenge or seek to improve upon development of immunological reagents by utilizing novel theoretical concepts, approaches, methodologies, or instrumentation? Are the concepts, strategies, or instrumentation limited to a single reagent application or specificity or applicable in a broader sense? Is a refinement or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach  

Are the overall strategy, methodology, analyses, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the Resource and the research community it will serve? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the program, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? Are an appropriate plan for workflow and a well-established timeline proposed? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of vertebrate animals or human subjects?

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

Specific for this FOA: Are the plans for proposed development, production, evaluation, quality control and assurance procedures adequate? Does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the Resource? Are the plans or systems for electronic data management and tracking of requests, shipments, and inventory appropriate? Is the overall management plan well-reasoned and appropriate? Is the plan for development and maintenance of a public website and other proposed services appropriate? Are plans for community outreach appropriate?

Environment  

Will the institutional environment in which the Resource will operate contribute to the probability of success in facilitating the research programs it serves? Are the institutional support, equipment and other physical resources available to the investigators adequate for the Resource proposed? Will the Resource benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling?

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.

Reagent Sharing Plan

Are the plans for sharing with the scientific research community all reagents, products, assays, methodologies, and protocols developed with Resource funding reasonable?

Protections for Human Subjects  

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan  

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

Vertebrate Animals  

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

Biohazards  

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

Resubmissions  

Not Applicable

Renewals  

For Renewals, the committee will consider the progress made in the last funding period.

Revisions  

Not Applicable

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  

Not Applicable

Select Agent Research  

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

Resource Sharing Plans  

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

Authentication of Key Biological and/or Chemical Resources:  

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

Budget and Period of Support  

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

2. Review and Selection Process

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

As part of the scientific peer review, all applications will receive a written critique.

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

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

3. Anticipated Announcement and Award Dates

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

Section VI. Award Administration Information

1. Award Notices

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

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

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

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

2. Administrative and National Policy Requirements

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

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. HHS provides guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

• Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment. Please see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html; https://www2.ed.gov/about/offices/list/ocr/docs/shguide.html; and https://www.eeoc.gov/eeoc/publications/upload/fs-sex.pdf. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

• Recipients of FFA must also administer their programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws. Collectively, these laws prohibit exclusion, adverse treatment, coercion, or other discrimination against persons or entities on the basis of their consciences, religious beliefs, or moral convictions. Please see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

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

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 Part 75, 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:

• Engaging the scientific community to assess or anticipate their reagent needs.
• Providing the NIAID Program Official with, at a minimum, a quarterly assessment of the aggregate value of each new reagent proposed for development by the PD(s)/PI(s), research community or NIAID, that considers scientific justification of need; time, personnel, and resource requirements; feasibility; and necessary performance milestones.
• Cooperating with the NIAID Program Official, other NIAID staff members and NIAID appointed scientific advisors in periodic or annual evaluation of the Resource.
• Providing data and budgetary information regarding Resource activities as requested by the NIAID Program Official.
• Identifying opportunities for collaboration with other investigators in order to optimize the development and evaluation of reagents for the Resource.
• Developing a final transition plan in collaboration with, and when requested by, the NIAID Program Official for the transfer of Resource activities and resources to the new grantee institution.
• Negotiating Material Transfer Agreements with donor institutions in a timely manner.
• Ensuring management of Materials Transfer Agreements and Intellectual Property Rights, with commercialization rights, for reagents developed under the Resource that will remain readily accessible to the NHP research community consistent with the goals of this FOA. This includes receiving or developing materials/reagents under terms that permit continued access via the Resource, even if the award is relinquished.
• Maintaining a succession plan that addresses potential award leadership changes.
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

• The NIAID Program Official responsibilities will include, but not be limited to, the following activities:

• Monitoring the Resource progress and when appropriate, coordinating reviews by NIAID-appointed external scientific advisors and other NIAID program staff.
• Providing NIAID approvals to the PD(s)/PI(s) for new reagent development and, when applicable, approval for provision of reagents to investigators.
• In rare circumstances, such as a public health emergency, providing NIAID approvals for reagents targeting infectious disease agents or their cellular receptors.
• Assisting the PD(s)/PI(s) in identifying collaborators, sources, or resources.
• Advising on management and technical issues.
• Assisting in promoting and encouraging the use of the Resource and the sharing of unique reagents from the research community with the Resource.
• Assisting in maintenance of overall scientific balance commensurate with emerging research opportunities and NIAID priorities.

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

Areas of Joint Responsibility include:

• None; all responsibilities are divided between awardees and NIH staff as described above.

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

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

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

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

Section VII. Agency Contacts

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threatensubmission by the due date, and post-submission issues)

Finding Help Online:http://grants.nih.gov/support/(preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email:[email protected](preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support(Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email:[email protected]

Julia Shaw, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3711
Email: [email protected]

Tara Capece, Ph.D., MPH
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-7854
Email: [email protected]

Joyce M. Addy
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-6628
Email: [email protected]

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.

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