It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

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

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

The harmonization of regulatory requirements to ensure that safe, effective, and high-quality medicines are developed and registered in the most resource-efficient manner is authorized by 21 USC  383 and 393, as amended by the Food and Drug Administration Modernization Act of 1997 (FDAMA).

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is a unique global association with the capability of bringing together pharmaceutical regulatory authorities and international pharmaceutical industry associations to harmonize scientific and technical aspects of drug registration. Harmonization of regulatory requirements for the marketing of pharmaceuticals facilitates many public health benefits that are critical to achieving FDA’s mission including: preventing duplication of clinical trials in humans, reducing the development times and improving efficiency for drug development, increasing patient access to medicines, minimizing the use of animal testing without compromising safety and effectiveness, and streamlining the regulatory assessment process for new drug applications.

ICH is a programmatic priority for the U.S. Food and Drug Administration (FDA) to advance FDA's ability to regulate the increasingly globalized pharmaceutical market. Working through its Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER), FDA has played a leading role in ICH since its inception in 1990. ICH was originally founded to harmonize pharmaceutical regulatory standards between the US, European Union and Japan and has since expanded to include additional pharmaceutical regulatory authorities and industry associations from around the world in response to the increasingly global face of drug development. ICH's mission is to achieve greater harmonization to ensure that safe, effective, and high-quality medicines are developed and registered in the most resource-efficient manner. This is accomplished through the development of internationally harmonized guidance documents that are implemented by regional pharmaceutical regulatory authorities and categorized into four main topic areas:

1. Quality Guidelines: Harmonization of requirements to support pharmaceutical quality including, but not limited to, the conduct of stability studies, defining relevant thresholds for impurities testing and a more flexible approach to pharmaceutical quality based on Good Manufacturing Practice (GMP) risk management.

2. Safety Guidelines: A comprehensive set of safety guidelines for non-clinical studies to uncover potential risks like carcinogenicity, genotoxicity and reprotoxicity.

3. Efficacy Guidelines: Harmonization of requirements concerned with the design, conduct, safety, and reporting of clinical trials. This set includes guidelines that also covers novel types of medicines derived from biotechnological processes and the use of pharmacogenetics/pharmacogenomics techniques to produce better targeted medicines.

4. Multidisciplinary Guidelines: Cross-cutting topics that do not fit uniquely into one of the Quality, Safety and Efficacy categories. This set includes specifications for the Common Technical Document (CTD) for regulatory submissions related to marketing applications, and the development of Electronic Standards for the Transfer of Regulatory Information (ESTRI).

In 2015, ICH was reformed and established as a legal entity in the form of a nonprofit association under Swiss law to meet the challenges of 21st century standards development and firmly position ICH's future work to continue to focus on technical standards harmonization informed by relevant expertise from regulatory agencies and regulated industry. The reforms have expanded opportunities for formal participation by additional pharmaceutical regulatory authorities beyond the three founding regions via the ICH Assembly and Working Groups. Since, the Association has grown to include participation of several additional pharmaceutical regulatory authorities and industry associations and is anticipated to continue to grow.

FDA is a Founding Member of ICH and remains committed to ICH's success as a science-based standards development organization to ensure global harmonization for safe, effective, and high-quality medicines. As exemplified in the past 25 years, FDA leadership and participation are an essential element for ICH's success.

The goals of this program are to develop and maintain a series of international guidelines for implementation according to each region’s requirements aimed at achieving the following:

1. Develop and register safe, effective, and quality medicines in a more efficient and cost

effective manner;

2. Prevent unnecessary duplication of clinical trials and minimize the use of animal testing without

compromising safety and effectiveness; and

3. Provide public assurance that the rights, safety, and well-being of subjects are protected during

clinical trials.

As new guidelines are developed, there is also a need to revise or clarify existing guidelines in view of new emerging technology and advancement of scientific understanding.

The goals are also to promote consistent implementation of the guidelines regionally and ensure sufficient understanding and interpretation of guidelines such as through the conduct of training or communications and outreach efforts.

Additionally, the objective is to make information readily available on ICH, ICH activities, and ICH guidelines to any country or company that requests the information and promote a mutual understanding of regional initiatives in order to facilitate harmonization processes related to ICH guidelines regionally and globally, and to strengthen the capacity of drug regulatory authorities and industry to utilize them.

These objectives will be accomplished by bringing together representatives from both pharmaceutical regulatory agencies and industries to establish guidelines.

Achieving these objectives requires bringing together pharmaceutical regulatory authorities from around the globe and international pharmaceutical industry associations. FDA is seeking to establish a cooperative agreement with ICH for its unique qualifications and experience in convening these global stakeholders and facilitating the development of internationally harmonized guidance. The goals of this collaboration are to advance harmonization of regulatory requirements to promote more efficient drug development and marketing and increased patient access to medicines.

ICH is composed of an Assembly, Management Committee (MC), Secretariat, and several working groups developing harmonized guidance in the areas of Quality, Efficacy, Safety, and Multidisciplinary areas. The ICH Assembly and MC are the governing and administrative bodies that oversee the harmonization activities of ICH. The MC has representatives from the six founding members, respectively representing the regulatory authority and the regulated industry in the United States, European Union, and Japan (FDA, PhRMA, EC, EFPIA, and MHLW, JPMA,), from the two standing members representing regulatory authorities in Switzerland and Canada (Swissmedic and Health Canada), and two standing observers (IFPMA and WHO). Additionally, the MC also includes a reserved number of seats for elected members. The Assembly includes all MC members as well as additional regional pharmaceutical regulatory authorities and industries who participate in ICH as Members and Observers.

The ICH Secretariat is responsible for the day-to-day management of the Association including coordinating ICH activities, convening face-to-face meetings and teleconferences, as well as providing support to the Assembly, MC, and the ICH working groups. Additionally, the ICH Secretariat provides administrative and project management support for the activities outlined below.

A. ICH Working Groups

For each of the technical topics that have been selected for harmonization in the first phase of activities, the MC appoints a working group to review the differences in requirements between regions and develop scientific consensus required to reconcile those differences.

The following types of ICH working groups can be established:

1. Expert Working Group (EWG): Charged with developing a harmonized guideline that meets the objectives in the Concept Paper and Business Plan.

2. Implementation Working Group (IWG): Tasked with developing a question and answer document and/or training materials to facilitate consistent implementation of a guideline.

3. Informal Working Group: Formed prior to any official ICH harmonization activity with the

objectives of developing a Concept Paper, as well as developing a Business Plan.

4. Discussion Group: Established to discuss specific scientific considerations or views on potential future harmonization projects.

The ICH Secretariat facilitates the establishment of the ICH working groups, provides administrative support throughout the process of harmonization, and coordinates the communication of progress of the working groups to the ICH Management Committee and Assembly. The ICH working groups work to develop a draft guideline and bring it through the various steps (outlined below) of the procedure which culminates in Step 5, the implementation of harmonized guidelines in the ICH regions.

Process of Harmonization

The procedure for harmonization of new ICH topics is initiated with the endorsement by the ICH Assembly of a new topic proposal and subsequent approval of a Concept Paper and Business Plan by the ICH Management Committee. An EWG or IWG with membership as specified by the ICH Assembly Rules of Procedure is subsequently established.

Step 1: Consensus building

The working group works to prepare a consensus draft of the technical document, based on the objectives set out in the Concept Paper. Work is conducted via e-mail, teleconferences and web conferences. If endorsed by the MC, the working group will also meet face-to-face at the biannual ICH meetings. Interim reports on the progress of the draft guideline are made on a regular basis. When consensus on the draft is reached within the working group, the technical experts will sign the Step 1 Experts sign-off sheet. The Step 1 Experts Technical Document with signatures is then submitted to the Assembly to request adoption under Step 2 of the ICH process.

Step 2a: Confirmation of consensus on the Technical Document

Step 2a is reached when the Assembly agrees, based on the report of the working group, that there is sufficient scientific consensus on the technical issues for the Technical Document to proceed to the next stage of regulatory consultation.

Step 2b: Adoption of draft Guideline by Regulatory Parties

On the basis of the Technical Document, the ICH Regulatory Parties will take the actions they deem necessary to develop the draft Guideline. Step 2b is reached when the regulatory parties sign-off the draft Guideline.

Step 3: Regulatory consultation and Discussion

Step 3 occurs in three distinct stages: regulatory consultation, discussion, and finalization of the Step 3 Expert Draft Guideline.

1. Regional regulatory consultation: The Guideline embodying the scientific consensus leaves the ICH process and becomes the subject of normal wide-ranging regulatory consultation by the ICH regulatory members of the Assembly. Regulatory authorities and industry associations in other regions may also comment on the draft consultation documents by providing their comments to the ICH Secretariat.

2. Discussion of regional consultation comments: After obtaining all comments from the consultation process, the working group works to address the comments received and reach consensus on what is called the Step 3 Experts Draft Guideline.

If the Rapporteur was from an Industry Party, following Step 2b a new Rapporteur from a Regulatory Party is appointed, preferably from the same region as the previous Rapporteur.

3. Finalization of Step 3 Experts Draft Guideline: If, after due consideration of the consultation results by the working group, consensus is reached amongst the experts on a revised version of the Step 2b draft Guideline, the Step 3 Expert Draft Guideline is signed by the experts of the ICH Regulatory Parties.

The Step 3 Expert Draft Guideline with regulatory signatures is submitted to the Assembly to request adoption at Step 4 of the ICH process.

Step 4: Adoption of an ICH Harmonized Guideline

Step 4 is reached when the regulatory members of the Assembly agree that there is sufficient consensus on the draft Guideline. The Step 4 Final Document is signed-off by the Assembly signatories for the Regulatory Parties of ICH as an ICH Harmonized Guideline at Step 4 of the ICH process.

Step 5: Implementation

Having reached Step 4 the harmonized guideline moves immediately to the final step of the process that is the regulatory implementation. This step is carried out according to the same national/regional procedures that apply to other regional regulatory guidelines and requirements, in the ICH member regions.

B. Convening of Meetings

The ICH Secretariat convenes face-to-face meetings when needed to advance harmonization projects. The ICH Assembly, Management Committee, and working groups hold two face-to-face meetings each year, in addition to several teleconferences throughout the year. Additionally, the ICH Management Committee holds an interim face-to-face meeting once per year. Further, additional meetings may be convened as needed. The purpose of these meetings is to identify and progress new topics for harmonization, revise/modify existing guidelines through amendments and update existing guidelines/adding standards to existing guidelines.

C. Training

As part of its effort to achieve globally harmonized implementation of ICH Guidelines, ICH is working on ensuring that high quality training is available based upon scientific and regulatory principles outlined in the ICH Guidelines. The ICH Secretariat coordinates the development of training materials through numerous avenues including: materials developed by ICH working groups, ICH Recognized Training Program Providers who develop in-person training programs on priority ICH Guidelines for regulators, industry and other stakeholders involved in drug development, and with ICH Training Associates developing online training materials, including case studies for prioritized guidelines.

D. Strategy

The ICH Secretariat maintains the annual and multi-annual strategic plans, refines and implements a strategic approach to address ICH guidelines training needs, and supports an ICH-driven mechanism to assess implementation and adherence to ICH guidelines through surveying and analysis of results.

E. Operations

The ICH Secretariat oversees the day-to-day operations of ICH. This includes management of aspects such as maintenance of the ICH trade mark, maintenance and implementation of the ICH Articles of Association and Procedures as necessary, maintenance of the ICH website, etc.

F. Communication

The ICH Secretariat oversees many of the ICH communication efforts such as the publication of content on the ICH website, email communications to the ICH members and observers, and implementation of ICH s transparency policy and efforts to increase the user-friendliness and functionalities of the ICH website with more accessible information on training.

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

 

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

International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)

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

Applicant Organizations

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

•         Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
•         System for Award Management (SAM) 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.
• o   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 FDA support.

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

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

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

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

•         A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
•         A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

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.

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

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

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

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.

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:

•         Applications requesting multiple years of support must complete and submit a separate detailed budget breakdown and narrative justification for each year of financial support requested.
•         Indirect costs under grants to foreign and international organizations will be funded at a fixed rate of 8 percent of modified total direct costs (MTDC), exclusive of tuition and related fees, direct expenditures for equipment, and subawards in excess of $25,000.

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.

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

•         Generally, Resource Sharing Plans are expected, but they are not applicable for this FOA.

Appendix:

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

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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

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

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

See Part 2. 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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

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

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

See more tips for avoiding common errors.

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

Post-submission materials are those submitted after submission of the grant application but prior to objective review. They are not intended to correct oversights or errors discovered after submission of the application. FDA accepts limited information between the time of initial submission of the application and the time of objective review. Applicants must contact the assigned Grants Management Specialist to receive approval, prior to submitting any post submission materials. Acceptance and/or rejection of any post submission materials is at the sole discretion of the FDA. Any inquiries regarding post submission materials should be directed to the assigned Grants Management Specialist.

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

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

The extent to which the applicant describes the magnitude of the potential impact on global health by advancing harmonization of technical requirements for registration of pharmaceuticals for human use.

(a) The extent to which the applicant demonstrates success in leading and coordinating multilateral harmonization efforts, projects, and collaborative efforts among international drug regulators and pharmaceutical industry.

(b) The extent to which the applicant describes its experience in dissemination and communication of information on harmonized guidelines, and facilitation of the adoption of new or improved technical research and development approaches.

(a)The extent to which the applicant provides clear goals, objectives, and intended outcomes that align with an operational plan for identifying, supporting, developing, conducting, and coordinating global research efforts to support harmonization of technical requirements for registration of pharmaceuticals for human use; developing educational papers that summarize research; creating a mechanism and technical support for timely sharing of research among regulators and industry; and coordinating a network of regulators and industry to develop technical requirements.

(b)The extent to which the applicant describes how each of the proposed sub-activities will address the overall purpose of this grant and adhere to the Program priorities.

(a)The extent to which the management plan is adequate to achieve the objectives of the proposed project on time and within budget, including clearly defined responsibilities, timelines, and milestones for accomplishing project tasks.

(b)What is the background, expertise, and administrative experience of key project staff who will direct, manage, and administer the program and/or identify key hires that will be necessary to carry out the program and is it appropriate?

The extent to which the applicant documents strong capacity for managing drug regulatory harmonization work among regulatory authorities and pharmaceutical industry particularly in the European Union, Japan, and the United States.

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

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan 

When the proposed project involves human subjects and/or FDA-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.

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.

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.

Not Applicable.

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

Not Applicable.

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.

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).

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).

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.

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

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

As part of the objective review, all applications:

•         Will receive a written critique.

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

The following will be considered in making funding decisions:

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

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

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.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

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

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

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights 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 FDA 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.
•         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), FDA awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a 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 section 75.205 HHS awarding agency review of risk posed by applicants. This provision will apply to all FDA grants and cooperative agreements.

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

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

Certificates of Confidentiality 42 U.S.C. 241(d)

Awardees are responsible for complying with all requirements to protect the confidentiality of identifiable, sensitive information that is collected or used in biomedical, behavioral, clinical, or other research (including research on mental health and research on the use and effect of alcohol and other psychoactive drugs) funded wholly or in part by the Federal Government.  See 42 U.S.C. 241(d).  All research funded by FDA, in whole or in part, that is within the scope of these requirements is deemed to be issued a Certificate of Confidentiality through these Terms and Conditions.   Certificates issued in this manner will not be issued as a separate document. 

Awardees are expected to ensure that any investigator or institution not funded by FDA who receives a copy of identifiable, sensitive information protected by these requirements, understand they are also subject to the requirements of 42 U.S.C. 241(d).  Awardees are also responsible for ensuring that any subrecipient that receives funds to carry out part of the FDA award involving a copy of identifiable, sensitive information protected by these requirements understand they are also subject to subsection 42 U.S.C. 241(d).

Additional terms and conditions regarding FDA regulatory and CDER programmatic requirements may be part of the Notice of Award.

Reporting Requirements:

All FDA grants require both Financial and Performance reporting.

Financial Reporting:

A. Cash Transaction Reports

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

B. Financial Expenditure Reports

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

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

Performance Progress Reporting:

When multiple years (more than one budget period) are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually as required in the Notice of Award. Annual RPPRs must be submitted using the RPPR module in eRA Commons. The annual RPPR must include a detailed budget. Annual RPPRs are due no later than 60 days prior to the start of the next budget period.

Failure to submit timely reports may affect future funding. Additional Financial and Performance Progress reports may be required for this award. Any additional reporting requirements will be listed under Section IV Special Terms and Condition of the Notice of Award.

Salary Caps:

None of the funds in this award shall be used to pay the salary of an individual at a rate in excess

of the current Executive Level II of the Federal Executive Pay Scale.

Acknowledgment of Federal Support:

When issuing statements, press releases, publications, requests for proposal, bid solicitations and other documents --such as tool-kits, resource guides, websites, and presentations (hereafter statements )--describing the projects or programs funded in whole or in part with FDA federal funds, the recipient must clearly state:

1. the percentage and dollar amount of the total costs of the program or project funded with federal money; and,

2. the percentage and dollar amount of the total costs of the project or program funded by non-governmental sources.

When issuing statements resulting from activities supported by FDA financial assistance, the recipient entity must include an acknowledgement of federal assistance using one of the following statements.

If the FDA Grant or Cooperative Agreement is NOT funded with other non-governmental sources:

This [project/publication/program/website, etc.] [is/was] supported by the Food and Drug Administration (FDA) of the U.S. Department of Health and Human Services (HHS) as part of a financial assistance award [FAIN] totaling $XX with 100 percent funded by FDA]/HHS. The contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by FDA/HHS, or the U.S. Government.

If the FDA Grant or Cooperative Agreement IS partially funded with other nongovernmental sources:

This [project/publication/program/website, etc.] [is/was] supported by the Food and Drug Administration (FDA) of the U.S. Department of Health and Human Services (HHS) as part of a financial assistance award [FAIN] totaling $XX with XX percentage funded by FDA/HHS and $XX amount and XX percentage funded by non-government source(s). The contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by FDA/HHS, or the U.S. Government.

The federal award total must reflect total costs (direct and indirect) for all authorized funds (including supplements and carryover) for the total competitive segment up to the time of the public statement. Any amendments by the recipient to the acknowledgement statement must be coordinated with FDA. If the recipient plans to issue a press release concerning the outcome of activities supported by FDA financial assistance, it should notify FDA in advance to allow for coordination.

Additional prior approval requirements pertaining to Acknowledgement of Federal Support, publications, press statements, etc. may be required, and if applicable, will be listed under Section IV Special Terms and Condition of the Notice of Award.

Prior Approval:

All prior approval requests must be submitted using the Prior Approval module in eRA Commons. Any requests involving budgetary issues must include a new proposed budget and a narrative justification of the requested changes. If there are any questions regarding the need or requirement for prior approval for any activity or cost, the grantee is to contact the assigned Grants Management Specialist prior to expenditure of funds. The following activities require prior approval from FDA:

1. Carryover of Unobligated Balances

2. No Cost Extensions

3. Change in Grantee Organization

4. Significant Rebudgeting

5. Change in Scope or Objectives

6. Deviation from Terms and Conditions of Award

7. Change in Key Personnel which includes replacement of the PD/PI or other key personnel as specified on the NoA.

8. Disengagement from the project for more than three months, or a 25 percent reduction in time devoted to the project, by the approved PD/PI. No individual may be committed to more than 100% professional time and effort. In the event that an individual's commitment exceeds 100%, the grantee must make adjustments to reduce effort. For FDA-sponsored projects, significant reductions in effort (i.e., in excess of 25% of the originally proposed level of effort) for the PD/PI and key personnel named on named on this Notice of Award must receive written prior approval from FDA.

Additional prior approval requirements may be required for this award, and if applicable, will be listed under Section IV Special Terms and Condition of the Notice of Award.

Audits and Monitoring:

Audit Requirements:

1. Recipients of Federal funds are subject to annual audit requirements as specified in 45 CFR 75.501 (https://www.ecfr.gov/cgi-bin/retrieveECFR?gp=1&SID=8040c4036b962cc9d75c3638dedce240&ty=HTML&h=L&r=PART&n=pt45.1.75#se45.1.75_1501). Grantees should refer to this regulation for the current annual Federal fund expenditure threshold level which requires audit.

2. Foreign recipients are subject to the same audit requirements as for-profit organizations (specified in 45 CFR 75.501(h) through 75.501(k).

3. For-profit and foreign entities can email their audit reports to AuditResolution@hhs.gov or mail them to the following address:

U.S. Department of Health and Human Services

Audit Resolution Division, Room 549D

Attention: Robin Aldridge, Director

200 Independence Avenue, SW

Washington, DC 20201

Monitoring:

Recipients are responsible for managing the day-to-day operations of grant-supported activities using their established controls and policies, as long as they are consistent with Federal, DHHS and FDA requirements. However, to fulfill their role in regard to the stewardship of Federal funds, FDA monitors our grants to identify potential problems and areas where technical assistance might be necessary. This active monitoring is accomplished through review of reports and correspondence from the recipient, audit reports, site visits, and other information available to FDA.

1. Desk review: FDA grants monitoring specialists will periodically reach out to recipients to request information for the completion of desk reviews. Requested information may include:

•         Policies and procedures
•         List of grant expenditures
•         Accounting records
•         Supporting documents (e.g., invoices, receipts, paystubs, timesheets, contracts, etc.)
•         Financial statements
•         Audit reports
•         Other related documentation

2. Site visits: FDA will conduct site visits when necessary and will notify the recipient with reasonable advance notice of any such visit(s).

3. Foreign entities: All Foreign entities are subject to the same monitoring requirements as domestic entities. Foreign entities covered under immunity Executive Orders will provide supporting documents for monitoring requirements unless such an action is a violation of the Executive Orders. Recipients may discuss with the FDA to come up with an alternate approach to satisfy the award monitoring requirements.

All recipients will make reasonable efforts to resolve issues found, including audit findings. Successful resolutions to issues are important as they are part of the grant performance review. All recipients are responsible for submitting all requested information in an expeditious manner. Failure to submit timely reports and/or respond to inquiries from FDA may affect future funding or enforcement actions, including withholding, or conversion to a reimbursement payment method.

Financial Conflict of Interest (FCOI):

This award is subject to the Financial Conflict of Interest (FCOI) regulation at 42 CFR Part 50 Subpart F.

Closeout Requirements (when applicable):

A Final Research Performance Progress Report (FRPPR), Final Federal Financial Report SF-425, Final Invention Statement HHS-568 (if applicable), Tangible Personal Property Report SF-428 (if applicable), and Statement of Disposition of Equipment (if applicable) must be submitted within 90 days after the expiration date of the project period. All closeout documents must be submitted electronically in eRA Commons.

The Final FFR must indicate the exact balance of unobligated funds and may not reflect unliquidated obligations. There must be no discrepancies between the Final FFR expenditure data and FFR cash transaction data in the Payment Management System (PMS). It is the recipient's responsibility to reconcile reports submitted to PMS and to the FDA.

Program Income:

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

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

Any Program Income generated during the Project Period of this grant by the grantee or sub-grantee will be treated as identified below.

Treatment of Program Income:

Other:

This award is subject to the requirements of 2 CFR Part 25 for institutions to maintain an active registration in the System of Award Management (SAM). Should a consortium/subaward be issued under this award, a requirement for active registration in SAM must be included.

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 with cumulative total value greater than $10,000,000 must report and maintain information 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 the Federal Awardee Performance and Integrity Information System (FAPIIS)). Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75.

Cooperative Agreement Terms and Conditions of Award

The purpose of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Program (ICH) is to provide support in convening leading global drug regulatory agencies and pharmaceutical manufacturer associations to achieve greater harmonization of technical standards to ensure that safe, effective, and high-quality medicines are developed and registered in the most resource-efficient manner. The outcome of this effort will be a series of internationally recognized guidelines aimed at quality, safety, efficacy, and other multidisciplinary areas.

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

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

2.A.1. Principal Investigator Rights and Responsibilities

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

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

Additionally PD/PIs will:

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

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

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

2.A.2. FDA Responsibilities

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

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

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

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

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

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

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 threaten submission by the due date, and post-submission issues)

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

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

Jill Adleberg
Center for Drug Evaluation and Research (CDER)
Telephone: 301-796-5259
Email: jill.adleberg@fda.hhs.gov

Shashi Malhotra

Office of Acquisitions & Grants Services (OAGS)

Food and Drug Administration

Telephone: 240-402-7592

Email: Shashi.Malhotra@fda.hhs.gov

Shashi Malhotra

Office of Acquisitions & Grants Services (OAGS)

Food and Drug Administration

Telephone: 240-402-7592

Email: Shashi.Malhotra@fda.hhs.gov

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

Awards are made under the authorization of 21 USC  383 and 393, as amended by the Food and Drug Administration Modernization Act of 1997 (FDAMA).