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

Background

Generic drug products demonstrate bioequivalence (BE) to the reference product by showing that they can deliver a similar amount of the drug to the site(s) of therapeutic action at a similar rate and extent as the reference drug product. The FDA has been researching the feasibility of alternative, scientifically valid methods, including in vitro approaches, to support an evaluation of BE for topical drug products. These research initiatives have supported the development of multiple draft product specific guidances for several topical drug products which have included an option to demonstrate BE using a comparative product characterization-based approach.

These in vitro, characterization-based BE approaches have been applicable to prospective generic products with formulations that have no difference in their components or composition relative to the reference product that may affect their local or systemic bioavailability (e.g. formulations that are qualitatively (Q1) and quantitatively (Q2) the same as the reference product), and which also have an arrangement of matter (Q3) that is similar to that of the reference product, typically within the range of variation characterized to exist among batches of the reference product. Further research is currently underway to evaluate the applicability of in vitro, characterization-based BE approaches to prospective generic products with formulations that have some differences in components or composition compared to the reference product, and/or which have differences in Q3 attributes that may be outside the range of variation characterized to exist among batches of the reference product. For example, sensitive instruments may discriminate differences in the rheological properties of topical semisolid drug products that may be imperceptible to patients, and which may not alter the retention of the product at the site of administration, or alter the function of the drug product; such differences between a test and reference product, although measurable by sensitive instruments, may not necessarily represent a potential failure mode for BE.

When a test product has the same Q1, Q2, and Q3 properties as the reference product, the risk of many potential failure modes for BE are essentially eliminated. However, these risks need to be better understood when considering the BE and therapeutic equivalence of a test product that has some Q1, Q2, and/or Q3 differences relative to the reference product. For example, if the occlusivity of a reference product formulation inhibits transepidermal water loss, increases skin hydration, and promotes healing, but if Q1, Q2 or Q3 differences between the test and reference product alter the occlusivity of the test product, then the therapeutic performance of the test product may be different relative to the reference product. As another example, if a given solvent activity of a reference product modulates the rate at which volatile components are lost from the product formulation in such a way that the cooling sensation derived from the endothermic evaporative metamorphosis of the reference product provides therapeutic relief, then Q1, Q2 or Q3 differences between the test and reference product may alter the therapeutic performance of the test product relative to the reference product. Equally, changes in the rheology, occlusivity, solvent activity or other properties of a product across its shelf life may alter its therapeutic performance over time.

To advance FDA's mission to make high quality, safe and effective drug products available to the American public while supporting innovation, it is essential to explore the potential utility of novel, efficient standards for BE that may be applicable to prospective generic topical drug products that may not have the same formulation as the reference product. To support this goal, it is necessary to investigate the qualitative and functional characteristics of compositionally different topical formulations and to understand when differences in product quality attributes may be clinically

meaningful and can impact the therapeutic equivalence.

The objective of this work is to support research relevant to topical semisolid drug products that will help to elucidate the relationship between a product's quality attributes and its functional properties and demonstrate the impact of product aging on the quality and sensory attributes of topical semisolid dosage forms. A specific objective is to elucidate how characterizations of the arrangement of matter, including the rheology, occlusivity and evaporative metamorphosis of different topical dosage forms may correlate with and/or be predictive of sensorial differences perceived by human subjects (or patients). It is not sufficient to only characterize physicochemical and structural qualities of semisolid formulations; this research specifically necessitates the assessment of complex human sensory perceptions about semisolid dosage forms (formulations) that can be correlated with the physicochemical and structural qualities of those same formulations.

Upon the successful completion of this research, it should be possible to predict, based upon product quality characterizations like particle size distribution, texture analysis, tribology, evaporative/drying rate, and other Q3 characteristics whether test and reference products that may be compositionally different are likely to provide comparable perceptions of grittiness, silky-smoothness, cooling sensation, or other functional properties that may be relevant to the therapeutic performance of a drug product or to patient perceptions of equivalence.

Compositional differences between topical formulations may have the potential to alter the physical and structural attributes of the dosage form in ways that may not only affect the bioavailability of a drug but also functional properties of a product (like providing a cooling sensation) that may have the potential to impact a patient's perception of therapeutic effect. The intent of this funding opportunity is to systematically elucidate the fundamental mechanistic principles underlying the complex interplay of such factors and to identify or develop approaches to characterize and compare information about compositionally different formulations that may be clinically relevant.

The expectation is that the investigators not only have expertise in semisolid formulation manufacturing and Q3 characterization, but can conduct human research studies that characterize people's perceptions about various specific properties of topical dosage forms, and about the perceived sameness of comparator products/formulations. Investigators are expected to have generated preliminary data to demonstrate their understanding of the sensory attributes for different topical dosage forms that have the potential to impact a product's therapeutic equivalence, and must have demonstrated experience with identifying and characterizing relevant Q3 attributes of topical semisolid products/formulations that can be correlated with sensorial attributes perceived by humans.

Investigators would be expected to manufacture topical formulations that are intentionally and systematically varied in Q1, Q2, and/or Q3 attributes, which would then be characterized using a variety of relevant Q3 characterization tests. Investigators would also be expected to generate clinical results by evaluating these formulations in product testing focus groups, using appropriate controls, study designs, and questionnaires. Based upon the results of the physical and structural product quality tests, and the questionnaire responses, investigators would be expected to evaluate what quality tests correlate with and are predictive of sensorial differences perceived by human subjects (or patients). The expectation is that some preliminary data has been generated in vitro for at least one topical dosage form so that the investigators are demonstrably well ready and able to initiate the clinical research that is a key focus of this funding opportunity, as well as to advance similar in vitro and in vivo studies with other topical dosage forms during this this cooperative agreement.

The deliverables would include a body of evidence to support the acceptability of Q3 differences for prospective generic products that may not have the same formulation as the reference product, but which may have similar Q3 attributes.  The outcomes of this research should help to identify ranges in which certain product quality attributes may vary without producing clinically meaningful differences.

The rationale for offering the funding opportunity as a two-year award is to afford sufficient time and resources to be able to research and evaluate data from multiple systematically varied topical formulations (of multiple different dosage forms), to complete comprehensive Q3 characterizations of each formulation, to conduct sensorial testing of those formulations with human subjects who would evaluate the look and feel of the same series of topical formulations, and to monitor the changes in Q3 and sensorial attributes of these topical products across their shelf-life. While the proposal would benefit from specific plans relating to the types of formulations to be evaluated, and the types of quality and sensorial tests that will be utilized for the analysis, the expectation is that the specific formulations that would ultimately be manufactured and tested would be selected in collaboration with the FDA. The intent of the cooperative agreement is that the award recipient will work collaboratively with FDA scientists to refine the research strategy, develop study designs and protocols, orchestrate study conduct, analyze data, and publish the results.

NOTE: The expectation is that evidence of existing data generated in vitro for at least one topical dosage form will be submitted in the application; this evidence will be considered by when scoring the 'Significance' of the application. The expectation is also that the data generated as an outcome of this research award, including but not necessarily limited to any individual replicate/subject-level data (not just summary results), any model constructs and data sets, and/or any computer code that represents an outcome of the award should be shared with the FDA Office of Generic Drugs (OGD) prior to the completion of the award period, and it is strongly preferred that FDA would explicitly be granted permission to make such data publicly available after a reasonable amount of time following the completion of the award period (e.g., 1 year after the end of the award period); the applicant's Data Sharing Plan will specifically be considered when scoring the 'Significance' of the application.

Specific areas of scientific interest would include research to:

1. Identify the product quality tests that would characterize the qualities of topical products relevant to their sensorial attributes, and sensorial tests that would evaluate subjects' perceptions about the formulations.

3. Collaborate with FDA scientists to refine the research strategy and to finalize the systematically varied series of formulations for each topical dosage (including a topical ointment and topical foam).

4. Evaluate these series of formulations clinically in human subjects (or patients) using product testing focus groups.

5. Based upon the results of the physico-structural product quality tests, and the questionnaire responses, evaluate what quality tests correlate with and are predictive of sensorial differences perceived by human subjects (or patients). 

6. Iteratively repeat the steps above, as needed, to achieve the objectives of the award for multiple topical dosage forms.

7. Evaluate the effect of product ageing on quality and sensorial attributes of the manufactured formulations.

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.

•         University of Queensland

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.
• 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, with the following additional requirements:

•         For field 4. a. Federal Identifier - The Federal Identifier is required. Include only the IC and serial number of the previously assigned award number (e.g., use FD006700 from 5U01FD006700-02).
•         For field 8. TYPE OF APPLICATION - applicant must mark 'RENEWAL'.

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.
• If an applicant is requesting indirect costs as part of their budget, a copy of the most recent Federal indirect cost rate or F&A agreement must be provided as part of the application submission. This agreement should be attached to the RESEARCH & RELATED Other Project Information Component as line #12 'Other Attachments'.
• If the applicant organization has never established an indirect cost rate and/or does not have a negotiated Federal indirect cost rate agreement, a de minimis indirect cost rate of 10 percent (10%) of modified total direct costs (MTDC) will be allowed. MTDC means all direct salaries and wages, applicable fringe benefits, materials and supplies, services, travel, and subaward and subcontracts up to the first $25,000 of each subaward or subcontract. MTDC excludes equipment, capital expenditures, charges for patient care, rental costs, tuition remission, scholarships and fellowships, participant support costs and the portion of each subaward and subcontract in excess of $25,000.
• Indirect/F&A 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. (With the exception of the American University of Beirut and the World Health Organization, which are eligible for full F&A cost reimbursement). Awards to domestic organizations with a foreign or international consortium participant may include 8 percent of 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, with the following additional requirements:

Research Strategy: The Research Strategy should include a brief Progress Report that summarizes Progress to Date and accomplishments achieved during the current funding period. The Progress Report should include a summary of the specific aims of the previous project period and the importance of the findings, progress made towards achievements, explanation on any significant changes to the specific aims and any new directions.

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

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

Appendix:

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

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 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

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 and 45 CFR 75.

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.

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

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

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

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

If the project involves human subjects and/or 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?

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

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.

When the proposed project involves human subjects and/or 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.

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

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

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 recipient’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions and in the Notice of Award. 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.

Institutional Review Board or Independent Ethics Committee Approval: For projects that involve Human Subjects and/or Clinical Trials Research, Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in FDA-funded studies, the awardee must provide FDA copies of documents related to all major changes in the status of ongoing protocols.

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. For information about FDA's commitment to supporting a safe and respectful work environment and what FDA's expectations are for institutions and the individuals supported on FDA-funded awards, please see https://www.fda.gov/science-research/about-science-research-fda/fda-sexual-harassment-policy-concerning-extramural-research.
•         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 Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all FDA grants and cooperative agreements.

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

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

Additional terms and conditions regarding FDA regulatory and 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.

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).

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.

For grant awards not covered under Expanded Authorities, Carryover and No Cost Extension (NCE) requests will require prior approval. All Carryover and NCE requests should be submitted using the Prior Approval module in eRA Commons. ****Please review the section on Expanded Authorities to determine if this award is covered/not covered under Expanded Authorities and whether prior approval is needed for carryover and no cost extension requests.****

The following activities require prior approval from FDA on all awards:

1. Change in Grantee Organization

2. Significant Rebudgeting

3. Change in Scope or Objectives

4. Deviation from Terms and Conditions of Award

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

6. 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 [email protected] 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). The expended funds reported on the Final FFR must exactly match the disbursements reported on the grantee's report to the Payment Management System and the charge advances in 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:

Prohibition on certain telecommunications and video surveillance services or equipment:

(a) As described in CFR 200.216, recipients and subrecipients are prohibited to obligate or spend grant funds (to include direct and indirect expenditures as well as cost share and program) to:

(1) Procure or obtain,

(2) Extend or renew a contract to procure or obtain; or

(3) Enter into contract (or extend or renew contract) to procure or obtain equipment, services, or systems that use covered telecommunications equipment or services as a substantial or essential component of any system, or as critical technology as part of any system. As described in Pub. L. 115-232, section 889, covered telecommunications equipment is telecommunications equipment produced by Huawei Technologies Company or ZTE Corporation (or any subsidiary or affiliate of such entities).

i. For the purpose of public safety, security of government facilities, physical security surveillance of critical infrastructure, and other national security purposes, video surveillance and telecommunications equipment produced by Hytera Communications Corporation, Hangzhou Hikvision Digital Technology Company, or Dahua Technology Company (or any subsidiary or affiliate of such entities).

ii. Telecommunications or video surveillance services provided by such entities or using such equipment.

iii. Telecommunications or video surveillance equipment or services produced or provided by an entity that the Secretary of Defense, in consultation with the Director of the National Intelligence or the Director of the Federal Bureau of Investigation, reasonably believes to be an entity owned or controlled by, or otherwise, connected to the government of a covered foreign country.

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.

Clinical Trials - Human Subjects Protections:

The Grantee/Principal Investigator (PI) is required to have a current Federal Wide Assurance (FWA) for the Protection of Human Subjects on file with the Office for Human Research Protections (OHRP), 1101 Wootton Parkway, Suite 200, Rockville, MD 20852, before conducting research that involves human subjects. Questions about FWAs should be directed to OHRP.

Research funded by this initiative must comply with federal regulations governing the protection of human subjects in research at 45 CFR Part 46 and may also be subject to FDA’s human subject protection regulations at 21 CFR Parts 50 & 56.   These regulations require that research involving human subjects must be approved by an IRB that must assess the risks of the research to the subjects and whether any risks of the research are minimized, the anticipated benefits of the research to the subjects, and the importance of the knowledge that may be reasonably expected to result. (See 45 CFR Part 46, available at https://www.hhs.gov/ohrp/regulations-and-policy/regulations/45-cfr-46/index.html).

The proposed research protocol should comply with ICHE6 Good Clinical Practice: Consolidated Guidance, available at https://www.fda.gov/media/93884/download. This guidance lays out an international ethical and scientific quality standard for designing, conducting, recording, and reporting trials that involve the participation of human subjects. Applicants are encouraged to review the regulations, guidance, and information sheets on human subject protection and good clinical practice available on FDA’s webpage on Clinical Trials and Human Subject Protection at https://www.fda.gov/science-research/science-and-research-special-topics/clinical-trials-and-human-subject-protection.

Clinical Trial - Human Subject Training for Key Personnel

The grantee/PI is responsible for ensuring that all key personnel receive appropriate training in their human subject protection responsibilities. Key personnel include all principal investigators, co-investigators, and performance site investigators responsible for the design and conduct of the study. HHS, FDA, and OGD PO do not require or endorse any specific education programs. Appropriate instructions might include, for example, the online tutorials offered by the NIH and OHRP, at https://grants.nih.gov/grants/policy/hs/training.htm and by OHRP at https://www.hhs.gov/ohrp/education-and-outreach/index.html

Within 30 days of the award, the PI must provide a letter that includes the names of the key personnel, the title of the human subjects protection education program completed by each of the key personnel, and a one-sentence description of the program. This letter should be signed by the PI and cosigned by the institutional signing official and sent to the FDA Project Officer, and to Grants Management Officer (GMO)/Specialist (GMS), whose names appear on the official Notice of Grant Award.

Clinical Trials - Protocol

The grant application must include a copy of the research/investigational plan or protocol in the grant application.

Clinical Trials - Informed Consent

Consent forms, assent forms, and any other information given to a subject should be included in the grant application, even if they are in draft form. All such documents should be attached in an appendix section. The applicant is referred to HHS and FDA regulations at 45 CFR 46.116 and 21 CFR 50.25 for details regarding the required elements of informed consent.

Clinical Trials - Monitoring

Data and safety monitoring of a clinical trial should be commensurate with the risks posed to the study participants and with the size and complexity of the study. In addition, the Grantee, and any third party engaged in supporting the clinical research, are responsible for oversight of data and safety monitoring, ensuring that monitoring systems are in place, that the quality of the monitoring activity is appropriate, and that the OGD PO is informed of recommendations resulting from monitoring activities.

Each proposed research study must have data and safety monitoring procedures in place to safeguard the well-being of study participants and to ensure scientific integrity. Monitoring must be performed on a regular basis throughout subject accrual, while study procedures are being conducted, and during follow-up periods. Information regarding data and safety monitoring should be included in the grant application or protocol.

The specific approach to monitoring will depend on features of the research study to be conducted (e.g., several levels of monitoring), such as having a Data and Safety Monitoring Board (DSMB), Study Monitoring Committee (SMC), and/or Independent Medical Monitor (IMM). Monitoring activities should be appropriate to the study, study population, research environment, and degree of risk involved. Guidance is available at: https://www.fda.gov/media/93884/downloadand https://www.fda.gov/regulatory-information/search-fda-guidance-documents/establishment-and-operation-clinical-trial-data-monitoring-committees

Clinical Trial - Study Monitoring Plan

The study protocol must include a section describing the proposed plan for interim data monitoring. This section should explain who will be responsible for interim monitoring (i.e., a Data Safety Monitoring Board (DSMB), a Safety Monitoring Committee ( SMC), or the study investigator), what data will be monitored (i.e., performance and safety data only vs. efficacy data as well), the timing of the first data review (e.g., "the first interim monitoring will occur when the initial 20 participants have completed the 6 month follow-up visit"), and the frequency of interim reviews (which will depend on factors such as the study design, interventions, and anticipated recruitment rate). The plan will specify "stopping guidelines" and other criteria, if appropriate, for the monitors to follow in their review of the interim data. Guidance on these topics is available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/establishment-and-operation-clinical-trial-data-monitoring-committees.

A preliminary monitoring plan must be submitted as part of the Research Plan section of the grant application for a clinical trial. The monitoring plan will be examined as part of the peer review process, and any comments and concerns will be provided to the applicant in a summary statement (a document which reflects Ad Hoc Reviewer comments on the application submitted for funding). OGD staff will work with the applicant to address concerns raised before the grant award is made.

Clinical Trials - Clinical Trials.gov

The Food and Drug Administration Amendments Act of 2007 (FDAAA) contains provisions that expanded the current database known as ClinicalTrials.gov to include additional requirements for individuals and entities, including grantees, who are involved in conducting certain clinical trials of drugs (including biological products) or devices. Such trials are referred to, in the statute, as applicable clinical trials.   These additional requirements include mandatory registration of certain applicable clinical trials, as well as reporting of results for certain applicable clinical trials for inclusion in the ClinicalTrials.gov database.  More detailed information on the definition of "applicable clinical trial" and the registry and results reporting requirements can be found at http://clinicaltrials.gov/ct2/manage-recs/fdaaa.

FDAAA also added new requirements concerning applicable clinical trials supported by grants from HHS, including FDA. Under these provisions, any grant or progress report forms required under a grant from any part of HHS, including FDA, must include a certification that the person responsible for entering information into ClinicalTrials.gov (the "responsible party") has submitted all required information to the database. There are also provisions regarding when agencies within HHS, including FDA, are required to verify compliance with the registration and results submission requirements of FDAAA before releasing funding to grantees. OGD program staff will provide additional information on these requirements, including the appropriate means by which to certify that a grantee has complied with the database requirements.

Clinical Trials - Data and Safety Monitoring Boards

The establishment of data and safety monitoring boards (DSMBs) may be appropriate for multi-site clinical trials depending on the risk to the study participants. See  https://www.fda.gov/regulatory-information/search-fda-guidance-documents/establishment-and-operation-clinical-trial-data-monitoring-committees and  https://www.fda.gov/media/75398/download

The Grantee/PI must adhere to the following processes for Grants involving Human Subject research from the FDA.

1.  The Grantee is required to have a current Federal Wide Assurance for the Protection of Human Subjects for its institution on file with the Office for Human Research Protections (OHRP), 1101 Wootton Parkway, Suite 200, Rockville, MD 20852, before conducting research that involves human subjects. Questions about FWAs should be directed to OHRP. A copy of the current FWA shall be included in the Grantee/PI's proposal.  Additionally, the IRB of record (local IRB) appears on the FWA needs to be registered with OHRP and be in active, good standing.

2.  Upon award, the OGD PO will arrange a meeting via telephone conference with the Grantee/PI and Study Coordinator to discuss requirements of the FDA Institutional Review Board (IRB), including the roles and responsibilities of the OGD PO, OGD Sponsor (if different from OGD PO) OGD Human Subject Protection (HSP) Liaison and Clinical Research Team (CRT).  Additionally, the discussion may include the determination of whether the research study’s IRB review would be better served through a joint review arrangement or through an IRB Authorization Agreement (IAA), in which one IRB relies upon the review of another qualified IRB as the responsible IRB for the research study.  The discussion may also include the determination of whether OGD is engaged in nonexempt human subject research.

3.  Following the meeting referenced above, the Grantee/PI shall submit the proposed study documents including, but not limited to the research protocol, informed consent, and recruitment advertisements to the OGD PO for review. The OGD PO, CRT and/or its designee shall review the submitted study documents to ensure completeness of the submission package. Following the review and sign-off by the CDER HSP Liaison and OGD supervisors, the submission package shall be submitted electronically to the FDA IRB. The Grantee/PI also shall submit the final, approved research study documents to the OGD PO.

4.  If the Grantee/PI has already received local IRB approval or exemption for the final study documents prior to the submission to FDA IRB, then a copy of the local IRB certification letter must be included in the submission package sent to the OGD PO, and the Grants Management Officer (GMO)/Specialist (GMS). If applicable, the Grantee/PI may submit the final research study documents to their local IRB at the same time as submission to FDA IRB and shall provide the local IRB approval letter to the OGD PO. This requirement would include proposed research that is exempt from IRB approval.  Please note: Certification of local IRB review, exemption or approval must include the following: the PHS/HHS application number, title of the project, and name of the program director/principal investigator, date of local IRB approval or exemption, and appropriate signatures. The PI must ensure that any protocol(s) are consistent with the research plan in the corresponding application.

5.  For research studies requiring review by the FDA IRB, the FDA IRB will review the research study documents, to assure that the rights and welfare of human subjects involved are adequately protected, and for compliance with all relevant regulations. The FDA IRB will also determine whether the proposed research is exempt under 45 CFR 46.104(b) and whether an investigational new drug application is required (see 21 CFR Part 312). Upon approval by the FDA IRB, the OGD PO and/or his/her designee will provide a copy of the FDA IRB’s letter, stating that it has reviewed and approved the proposed research study, to the Grants Management Specialist, and the Grantee/PI. If FDA IRB renders a decision other than approval of the proposed research study documents (i.e., approvable with stipulations or disapproval), the OGD PO and/or his/her designee will provide a copy of the FDA IRB’s letter to the Grantee/PI and will assist the Grantee/PI in revising the research study documents for re-submission to FDA IRB for review and approval.

6.  For research studies requiring review by the FDA IRB, the Grantee/Pl shall not advertise for, recruit, or enroll human subjects, or otherwise commence any research involving human subjects until the FDA IRB has reviewed and approved the proposed research study, but may begin other limited aspects of grant performance prior to receiving FDA IRB approval of the proposed research study (such as training, and development of protocol training documents, planning, communications, travel, etc.). Research involving human subjects may commence immediately upon the Grantee/PI receipt of the FDA IRB’s approval documentation.

7.  For research studies requiring review by the FDA IRB, failure to obtain FDA IRB approval of the proposed research study will result in termination of the grant. However, failure to obtain FDA IRB approval during FDA IRB’s initial review will not automatically result in termination of the grant. Instead, the grantee may correct any deficiencies identified during the FDA IRB review and resubmit the proposed research study to FDA IRB for a second review. The Grantee/PI is encouraged to solicit the FDA IRB’s input during the resubmission process via the OGD PO and/or HSP Liaison as mentioned above.

8.  The Grantee/PI shall seek FDA IRB (through the OGD PO) and local IRB review and approval whenever modifications, amendments, or other changes are made to the research study documents. Modifications and amendments include, but are not limited, to changes to the protocol, consent forms, recruitment materials, and the addition or deletion of investigators. Changes may be instituted immediately after the recipient has received both the local IRB and FDA IRB approval, unless the changes are necessary to eliminate apparent immediate hazards to the subject. The OGD PO and/or his/her designee will provide a copy of FDA IRB’s approval of the proposed changes to the Grantee/PI and the GMO/GMS.

9.  Quality Assurance monitoring will be performed (either remotely or via on-site visits) by the OGD PO, CRT and/or its designee to help ensure human subject protection throughout the conduct of the study and assess compliance with the regulations and the FDA IRB requirements that govern the conduct of research involving human subjects.

10.  The OGD CRT and/or its designee will provide the Grantee/PI, GMO/GMS, and CDER HSP Liaison with a report of all identified concerns related to human subject protections, along with suggested corrective actions. If concerns are identified, the Grantee/PI is responsible for providing responses to the corrective actions listed in the report to the OGD CRT, GMO/GMS and OGD PO, within two weeks of receipt. If a Steering Committee or Monitoring Board is established by the Grantee/recipient, in collaboration with the OGD PO, responses to the report must be routed through the Steering Committee and the Monitoring Board as established. Non-compliance with federal regulations and FDA IRB requirements may be reported to OHRP or CDER’s Office of Compliance. As warranted, FDA IRB in collaboration with the HSP Liaison will notify OHRP or CDER’s Office of Compliance of any regulatory concerns. The Grantee/PI must provide documentation that the QA report and revised study documents (if appropriate) have been submitted to their local IRB. The documentation should reflect that the local IRB is aware and indicate whether any further action is required. Copies of this documentation must also be provided to the Steering Committee, Monitoring Board, HSP Liaison, and to the OGD PO. This documentation will be forwarded to FDA IRB for review and documentation by the OGD PO and/or his/her designee.

11.  The Grantee/PI will provide a letter (certification of local IRB approval), at least annually, stating that the local IRB has reviewed and approved the continuation of the research performed under this grant. This letter shall be submitted to the GMO/GMS, and the OGD PO. The OGD PO will provide a letter, at least annually, stating that FDA IRB has reviewed and approved the continuation of the research performed under this grant if applicable. This letter shall be submitted to the Grantee/PI, and GMO/GMS.

12.  The Grantee/PI will submit all proposed modifications and amendments to any of the research study documents for research performed under this grant to the OGD PO with a copy to the HSP Liaison, for submission to FDA IRB for review and approval. Modifications and amendments include, but are not limited to, changes to the protocol, consent forms, recruitment materials, and the addition or deletion of investigators. Changes may be instituted immediately after the Grantee/PI has received both the local IRB (and FDA IRB if applicable) approval documentation, unless the changes are necessary to eliminate apparent immediate hazards to the subject.

13.  The grantee/PI or awardee institution is responsible for ensuring that all key personnel receive appropriate training in their human subject protection responsibilities. Key personnel include all principal investigators, co-investigators, study coordinators, and performance site investigators responsible for the design and conduct of the study (or as deemed Key Personnel by the PI). HHS, FDA, and OGD do not require or endorse any specific education programs. Information might be available at https://grants.nih.gov/policy/clinical-trials.htm and by OHRP at https://www.hhs.gov/ohrp/education-and-outreach/index.html

14.  Within 30 days of the award, the PI must provide a letter that includes the names of the key personnel, the title of the human subjects protection education program completed by each of the key personnel, and a one-sentence description of the program. This letter should be signed by the PI and cosigned by the institutional signing official and sent to OGD PO and GMO/GMS whose names appears on the official Notice of Grant Award (NGA).

15.  If it is determined that the proposed research study is not subject to 45 CFR Part 46, then the grant and programmatic file will be documented accordingly.

16.  The generated data and reports will contain de-identified information only, and the code to link subjects to subject IDs will be kept at the study site in a secure and controlled manner.  Under no circumstances, the PI will share any identifiable data and/or the code with the OGD PO and/or his/her designee will receive.

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

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

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: [email protected]

Tannaz Ramezanli, Pharm.D., Ph.D.
Center for Drug Evaluation and Research
U.S. Food and Drug Administration
Telephone: 301-348-1930
Email: [email protected]

Shashi Malhotra
Office of Acquisitions & Grants Services (OAGS)
Food and Drug Administration
Telephone: 240-402-7592
Email: [email protected]

Shashi Malhotra
Office of Acquisitions & Grants Services (OAGS)
Food and Drug Administration
Telephone: 240-402-7592
Email: [email protected]

All awards are subject to the terms and conditions, cost principles, and other considerations described in the HHS Grants Policy Statement, 45 CFR 75 and Notice of Award.

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