4 PUBLIC POLICY REQUIREMENTS, OBJECTIVES AND OTHER APPROPRIATION MANDATES
NIH grants are subject to requirements intended to ensure that recipient organizations handle their Federal awards
responsibly. Grantees are required to adopt and enforce policies that minimize the opportunity for improper
financial gain on the part of the organization, its employees, and organizations and individuals whom they may
collaborate, and that limit the potential for research results to be tainted by possible financial or other gain. In
addition, NIH grantees are expected to provide safe and healthful working conditions for their employees and foster
work environments conducive to high-quality research.
This chapter addresses public policy requirements, objectives, and other appropriation mandates applicable to NIH
awards. The term "public policy" indicates that the requirement is based on social, economic, or other
objectives or considerations that may be attached to the expenditure of Federal funds by grantees, consortium
participants, and contractors, in general, or may relate to the expenditure of Federal funds for research or other
In addition to cross-cutting requirements that some or all Federal agencies must apply to their grant programs, NIH
grantees are subject to requirements contained in the HHS annual appropriations act that apply to the use of NIH
grant funds, applicable provisions in other Federal agencies' appropriations acts, including Treasury, and other
Federal statutes. Some of those requirements are included here in a separate section titled Appropriation Mandates
since they have been included in the appropriations acts for several years with little or no change. Those
requirements may be changed or other requirements may be added in the future.
The public policy requirements, objectives, and appropriation mandates listed in Exhibit 4 apply to all NIH awards
with exceptions as noted.
4.1 Public Policy Requirements and Objectives
NIH intends to uphold high ethical, health, and safety standards in both the conduct of the research it funds and the
expenditure of public funds by its grantees. The public policy requirements specified in this section set many of
those standards. The signature of the AOR on the application certifies that the organization complies, or intends to
comply, with all applicable policies, certifications and assurances referenced (and, in some cases, included) in the
application instructions. The policies, certifications and assurances listed in this section may or may not be
applicable to the project, program, or type of applicant organization. Requirements/objectives are listed in
As noted in this section, some requirements may necessitate the submission of a separate document (e.g., human
subjects assurance, certification of IRB approval or institutional exemption, civil rights assurance). Applicants and grantees should take particular note
of these requirements (for example, see specific sections on Human Subjects
Protections and Civil Rights Protections), the absence or
inadequacy of which may delay an award or render an applicant ineligible for award.
The grantee is responsible for: 1) establishing and maintaining the necessary processes to monitor its compliance and
that of its employees, consortium participants, and contractors with these requirements; 2) taking appropriate
action to meet the stated objectives; and, 3) informing NIH of any problems or concerns.
If a grant is awarded on the basis of false or misrepresented information, or if a grantee does not comply with these
public policy requirements, NIH may take any necessary and appropriate action, including using any of the remedies
described in Administrative Requirements—Enforcement Actions
or other available legal remedies.
Exhibit 4 contains information to help the grantee determine what public policy requirements, objectives and
appropriations mandates apply to its activities and whether a requirement should be included in a consortium
agreement or a contract for routine goods or services under the grant (see Glossary
in Part I for definitions). The exhibit distinguishes between these types of transactions under a grant and
indicates (by "Y" for Yes or "NA" for Not Applicable) whether a given requirement normally would
apply. However, even if the exhibit indicates that a requirement is not applicable that requirement potentially
could be applicable in a specific situation, e.g., if a contract under a grant involves research activity.
Therefore, this exhibit should be used as general guidance only. The grantee should consult the terms and conditions
of its award and should contact the GMO if it has any question concerning the applicability of a particular public
policy requirement or objective.
Exhibit 4 also indicates where, in the NIHGPS, the individual public policy requirements, objectives and
appropriation mandates are covered in more detail. The grantee should also consult its attorney, as appropriate,
regarding particular questions about the governing statute or regulation as applied to its specific circumstances.
Other cited policies or documents may provide additional information.
In addition to the requirements addressed in this section, there are applicable NIH administrative requirements
outlined in the Administrative Requirements chapter.
Some programs may have special requirements and are covered in IIB.
Exhibit 4: Public Policy Requirements, Objectives and Appropriation Mandates *
Requirement, Objective, or Appropriation Mandate
Contractor under Grant (routine goods/services)
Acknowledgment of Federal Funding (Appropriation Mandate) 4.2.1
* NA: A designation of NA in this table indicates that a
particular requirement does not apply to an otherwise eligible grantee, consortium participant, or contractor or may
not apply because the type of activity covered is one not normally performed by such an entity.
4.1.1 Animal Welfare Requirements
The PHS Policy on Humane Care and Use of Laboratory Animals(PHS Policy) requires that an approved
Animal Welfare Assurance be on file with the Office of Laboratory Animal Welfare (OLAW) at the time of award for all
grantee organizations receiving PHS support for research or related activities using live vertebrate animals.
Grantee organizations must establish appropriate policies and procedures to ensure the humane care and use of
animals, and bear ultimate responsibility for compliance with the PHS Policy in all PHS supported activities.
The PHS Policy incorporates the U.S. Government Principles for the Utilization and Care of Vertebrate Animals
used in Testing, Research, and Training, and requires the grantee to maintain an animal care and use program
based on the Guide for the Care and Use of Laboratory Animals. An Institutional Animal Care and Use Committee
(IACUC) appointed by the Chief Executive Officer or designee, is federally mandated to oversee the institution's
animal program, facilities, and procedures (Public Law 99-158, Sec. 495).
The PHS Policy defines "animal" as any live, vertebrate animal used or intended for use in research,
research training, experimentation, biological testing or related purposes.
Applications from organizations proposing the use of animals are incomplete if they do not thoroughly address the use
of vertebrate animals required in the Research Plan of the application. If the involvement of animals is indefinite
at the time of application, the applicant should provide an explanation and indicate when it is anticipated that
animals will be used. If an award is made, prior to conducting any animal activities the grantee must submit to the
NIH awarding IC for prior approval the detailed information about the use of animals as required in the Research
Plan of the application, and meet the Assurance and IACUC approval requirements of the PHS Policy.
Noncompeting and competing awards issued on or after October 1, 2012 (with FY 2013 funding) are prohibited from using NIH funds to procure cats from USDA Class B dealers. The procurement of cats may only be from USDA Class A dealers or other approved legal sources.
No costs for activities with live vertebrate animals may be charged to NIH if there is not a valid Animal Welfare
Assurance and IACUC approval of the activity.
The PHS Policy does not supersede applicable State or local laws or regulations that impose more stringent standards
for the care and use of animals in research. All grantee organizations are required to comply, as applicable, with
the regulations (9 CFR, Subchapter A) issued by the U.S. Department of Agriculture under the Animal Welfare Act, as
amended, 7 U.S.C. 2131 et seq., and other Federal statutes and regulations relating to animals.
220.127.116.11 Animal Welfare Assurance Requirements
An Animal Welfare Assurance is the document submitted by an institution assuring institutional compliance with the
PHS Policy. OLAW is responsible for requesting, negotiating, approving or disapproving, and, as necessary,
restricting or withdrawing approval of Assurances.
When an applicant institution does not have an Animal Welfare Assurance, the Authorized Organization Representative's
signature on the application constitutes declaration that the institution will submit an Assurance when requested by
OLAW. Upon such request, the institution shall prepare the Assurance as instructed by OLAW and in accordance with
the PHS Policy, and the authorized IACUC shall review those components of the application related to the care and
use of animals. Except in certain circumstances, the Assurance must be submitted to and approved by OLAW in order
for the IC to award the grant. No costs for activities with live vertebrate animals may be charged to NIH grants in
the absence of a valid Assurance on file with OLAW.
If the prime grantee does not have an Assurance and the animal activities will be conducted at an Assured institution named as a performance site, the grantee must obtain an Inter-institutional Assurance from OLAW. Under the Inter-institutional
Assurance, the grantee and performance site agree that the research will be conducted under the auspices and program
of animal care and use of the performance site's Assurance.
18.104.22.168 Verification of IACUC Approval
NIH will delay an award for research involving live vertebrate animals until the grantee organization and all
performance sites are operating in accordance with approved Animal Welfare Assurances and the grantee has provided
verification of IACUC approval of those sections of the application that involve use of vertebrate animals. IACUC
approval must have been granted within three years of the budget period start date to be valid; however, IACUCs may
determine that continuing review on a more frequent basis is appropriate.
Verification of IACUC approval may be filed at any time before award in accord with Just-in-Time procedures, unless
required earlier by the IC. Therefore, following peer review and notification of impact score/percentile,
applicant organizations with approved Assurances may wish to proceed with IACUC review for those applications that
have not yet received IACUC approval and that appear to be in a fundable range.
It is an institutional responsibility to ensure that the research described in the application is congruent with any
corresponding protocols approved by the IACUC.
No costs for activities with live vertebrate animals may be charged to NIH grants if there is not a valid IACUC
Under consortium (subaward) agreements in which the grantee collaborates with one or more other organizations, the
grantee, as the direct and primary recipient of NIH grant funds, is accountable for the performance of the project,
the appropriate expenditure of grant funds by all parties, and all other obligations of the grantee as specified in
the NIHGPS (see Consortium Agreements chapter in IIB). The
animal welfare requirements that apply to grantees also apply to consortium participants and subprojects.
The primary grantee is responsible for including these requirements in its agreements with collaborating
organizations, and for ensuring that all sites engaged in research involving the use of live vertebrate animals have
an approved Animal Welfare Assurance and that the activity has valid IACUC approval. The approval of more than one
IACUC is not required if the grantee and performance site(s) have Assurances; the institutions may exercise
discretion in determining which IACUC reviews research protocols and under which institutional program the research
will be conducted.
22.214.171.124 Foreign Grantees and Foreign Performance Sites
Foreign grantees must provide OLAW with an Animal Welfare Assurance for Foreign Institutions. This constitutes
institutional assurance and certification of compliance with the applicable laws, regulations, and policies of the
jurisdiction in which the research will be conducted, and a commitment to follow the International Guiding
Principles for Biomedical Research Involving Animals. IACUC approval is not required of foreign
grantees; however, OLAW encourages foreign grantees to use the standards in the Guide for the Care and Use of
When the grantee is a domestic institution and performance sites are foreign (i.e., domestic grant with a foreign
component), PHS Policy requirements are applicable. Accordingly, the grantee remains responsible for animal activities
conducted at the foreign site and must provide verification of IACUC approval (i.e., certification that the activities
as conducted at the foreign performance site are acceptable to the grantee). The grantee IACUC may accept, as its
own, the approval of a foreign organization's IACUC; however, the grantee IACUC remains responsible for the review.
Additionally, the foreign site must obtain an Animal Welfare Assurance for Foreign Institutions as described in the
126.96.36.199 Reporting to OLAW
Reporting requirements under the PHS Policy include an annual report to OLAW describing any change in the
institution's program for animal care and use as described in the Assurance, changes in IACUC membership, and the
dates the IACUC conducted its semiannual evaluations of the institution's program and facilities. The IACUC, through
the institutional official signing the Assurance, must promptly report any serious or continuing noncompliance with
the PHS Policy, serious deviations from the Guide for the Care and Use of Laboratory Animals, and any
Charges to NIH grant awards for the conduct of live vertebrate animal activities during periods of time that the
terms and conditions of the grant award are not upheld are not allowable. Specific situations under which charges
are not allowable are:
The conduct of animal activities in the absence of a valid Animal Welfare Assurance on file with OLAW.
The conduct of animal activities in the absence of a valid IACUC approval of the activities. Absence of IACUC
approval includes failure to obtain IACUC approval, expiration, or suspension of IACUC approval.
Instances of serious noncompliance with section IV.F.3. of the PHS Policy, such as those mentioned above, are to be
reported to OLAW and the IC supporting the grant award. In cases where charges have been made for unauthorized
animal activities, appropriate adjustments must be made to the grant to remove those charges. NIH requires that
reports contain a certification that no unallowable costs were charged to NIH grant funds during a period of
noncompliance. If such a certification cannot be made, a detailed accounting of unallowable charges made to each
affected grant should be included with the report. If a detailed accounting has not been completed at the time of
reporting, a date when it will be provided should be included.
NIH expects grantees to continue to maintain and care for animals during periods when animal activities are conducted
in the absence of a valid Animal Welfare Assurance and/or IACUC approval. ICs may allow expenditure of NIH grant
funds for maintenance and care of animals on a case-by-case basis. Consultation with the IC is encouraged regarding
questions concerning allowable costs.
Before NIH may make an award to a domestic organization, the AOR must certify, by means of the signature on the
application, that the organization has on file with the HHS OCR a one-time Assurance of Compliance with the statutes
described in this subsection. The Assurance, Form HHS 690, is filed for the organization and is not required for
each application. If the application has been recommended for funding and the applicant organization does not have
an Assurance of Compliance on file, it will receive the required form and instructions for completion and submission
from the awarding IC. The HHS 690 also is available from GrantsInfo@nih.gov
or by telephone at 301-945-7573.
Domestic organizations that receive funding from grantees (including consortium participants and contractors under
grants) rather than directly from NIH, also are required to file an HHS 690. The applicant/grantee is responsible
for determining whether those organizations have the required Assurance on file and, if not, ensuring that it is
filed with OCR.
188.8.131.52 Civil Rights Act of 1964
Title VI of the Civil Rights Act of 1964 provides that no person in the
United States shall, on the grounds of race, color, or national origin, be excluded from participation in, be denied
the benefits of, or be subjected to discrimination under any program or activity receiving Federal financial
assistance. The HHS implementing regulations are codified at 45 CFR 80.
184.108.40.206 Education Amendments of 1972
Title IX of the Education Amendments of 1972 provides that no person in the
United States shall, on the basis of sex, be excluded from participation in, be denied the benefits of, or be
subjected to discrimination under any educational program or activity receiving Federal financial assistance. The
HHS implementing regulations are codified at 45 CFR 86.
220.127.116.11 Rehabilitation Act of 1973
Section 504 of the Rehabilitation Act of 1973, as amended, provides that no otherwise qualified handicapped
individual in the United States shall, solely by reason of the physical or mental impairment, be excluded from
participation in, be denied the benefits of, or be subjected to discrimination under any program or activity
receiving Federal financial assistance. These requirements pertain to the provision of benefits or services as well
as to employment. The HHS implementing regulations are codified at 45 CFR parts 84 and 85.
18.104.22.168 Age Discrimination Act of 1975
The Age Discrimination Act of 1975 prohibits discrimination on the basis of age in any program or activity receiving
Federal financial assistance. The HHS implementing regulations are codified at 45 CFR 91.
22.214.171.124 Limited English Proficiency
EO 13166, August 11, 2000, requires grantees receiving Federal financial assistance to take steps to ensure that
people with limited English proficiency can meaningfully access health and social services. A program of language
assistance should provide for effective communication between the service provider and the person with limited
English proficiency to facilitate participation in, and meaningful access to, services. The obligations of grantees
are explained on the OCR Web site at http://www.hhs.gov/ocr/civilrights/resources/specialtopics/lep/.
4.1.3 ClinicalTrials.gov Requirement
Applicants and grantees should familiarize themselves with the requirements of Title VIII, Sec. 801 of Public Law 110-85 (also known as the FDA Amendments Act of 2007 or FDAAA), with respect to registration and results reporting requirements that may apply to certain studies. In particular, grantees should be aware that if an applicable clinical trial is funded in whole or in part by an NIH grant or cooperative agreement, any application or progress report shall include a certification that the Responsible Party has made all required submissions to ClinicalTrials.gov. The NIH strongly encourages registration of all clinical trials, whether required by FDAAA or not. For additional information, see http://grants.nih.gov/ClinicalTrials_fdaaa/index.htm and http://www.clinicaltrials.gov.
126.96.36.199 Certificates of Confidentiality
Section 301(d) of the PHS Act provides that the Secretary may authorize people engaged in biomedical, behavioral,
clinical, or other research activities to protect the privacy of research subjects by withholding the names and
other identifying characteristics of those subjects from individuals not engaged in the research. Individuals that
have such authorization may not be compelled to disclose subjects' names or other identifying characteristics in any
Federal, State, or local civil, criminal, administrative, legislative or other proceeding. CoCs may be granted for
studies collecting information that, if disclosed, could have adverse consequences for subjects or damage their
financial standing, employability, insurability, or reputation. By protecting researchers from being compelled to
disclose information that would identify research subjects, CoCs contribute to achieving research objectives and
promote participation in studies by helping to ensure confidentiality and privacy to participants. Information on
CoCs is available on the NIH Web site at the CoC Kiosk at http://grants.nih.gov/grants/policy/coc/index.htm.
Requests for CoCs should be submitted to the GMO, and, subject to awarding IC review and approval, a certificate may
be issued pursuant to section 301(d).
Research subject protections under CoCs differ from those provided under the Health Insurance Portability and Accountability Act (HIPAA)
Privacy Rule 42 CFR parts 160 and 164, and under Section 543 of the PHS Act (see Confidentiality of Alcohol and Drug Abuse Patient Records below) by
protecting identifiable health information from forced disclosure (e.g., by court order). Therefore, researchers may
obtain CoCs to withhold (protect) information that otherwise may be subject to release without individual consent under the Privacy Rule or Section 543 of
the PHS Act.
188.8.131.52 Confidentiality of Alcohol and Drug
Abuse Patient Records
Section 543 of the PHS Act, as implemented in 42 CFR 2, requires that records of substance abuse patients be
kept confidential except under specific circumstances and purposes. These protections differ from those available to
patients under HIPAA and are intended to ensure that a patient in a drug or alcohol abuse program is not made more
vulnerable than a similar patient who does not seek treatment. The covered records are any information, written or
not, of a patient who has applied for or been given diagnosis or treatment for alcohol or drug abuse at a federally
assisted program and includes any individual who, after arrest on a criminal charge, is identified as an alcohol or
drug abuser in order to determine that individual's eligibility to participate in a program. This includes records
of the identity, diagnosis, or treatment of any patient which are maintained in connection with the performance of
any program or activity relating to substance abuse education, training, treatment, rehabilitation, or research,
which is conducted under an NIH grant. Except as authorized under a court order, no patient record may be used to
initiate or substantiate any criminal charges against a patient or to conduct any investigation of a patient. The
regulations also describe procedures to allow for nonvoluntary disclosure of certain information by persons engaged
in research on mental health, including research on the use and effect of alcohol and other psychoactive drugs.
184.108.40.206 Confidentiality of Patient Records: Health Insurance Portability and Accountability Act
HHS issued the final version of the "Standards for Privacy of Individually Identifiable Health Information"—the
Privacy Rule—on August 14, 2002. The Privacy Rule is a Federal regulation under the Health Insurance
Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health
information. It is administered and enforced by OCR, HHS. Those entities required to comply with the Privacy Rule
(classified under the rule as "covered entities") had until April 14, 2003 to do so (with the exception of
small health plans which have an extra year to comply).
Decisions about applicability and implementation of the Privacy Rule reside with the researcher and the grantee
organization. The OCR Web site (http://www.hhs.gov/ocr/) provides information
on the Privacy Rule, including the complete text of the regulation and a set of decision tools for determining
whether a particular entity is subject to the rule. An educational booklet, Protecting Heath Information in
Research: Understanding the HIPAA Privacy Rule, is available through OCR's Web site and also at http://privacyruleandresearch.nih.gov/. That Web site also
includes other educational materials including information specific to grants.
4.1.5 Controlled Substances
If controlled substances are proposed to be administered as part of a research protocol or if research is to be
conducted on the drugs themselves, applicants/grantees must ensure that the DEA requirements, including
registration, inspection, and certification, as applicable, are met. Regional DEA offices can supply forms and
information concerning the type of registration required for a particular substance for research use. The main
registration office in Washington, DC may be reached at 800-882-9539. Information also is available from the National Institute on Drug Abuse at
4.1.6 Debarment and Suspension
HHS regulations published in 2 CFR 376 implement the government-wide debarment and suspension system guidance (2
CFR 180) for HHS' non-procurement programs and activities. "Non-procurement transactions" include,
among other things, grants, cooperative agreements, scholarships, fellowships, and loans. NIH implements the HHS
Debarment and Suspension regulations as a term and condition of award. Accordingly, recipients of NIH grants ("primary
covered transactions"), including sponsoring institutions for Kirschstein-NRSA individual fellowships, are
required to determine whether it or any of its principals (as defined in 2
CFR 180.995 and 2
CFR 376.995) is excluded or disqualified from participating in a covered transaction (i.e., grant or
cooperative agreement) prior to entering into the covered transaction, i.e., prior to the drawdown of funds which
signals acceptance of the grant award. Grantees may decide the method and frequency by which this determination is made and may check excluded parties in SAM, although checking SAM is not required.
Prior to the drawdown of funds for each grant award, grantees must report to the funding IC if the grantee or any of
Are presently excluded or disqualified;
Have been convicted within the preceding three years of any of the offenses listed in 2 CFR 180.800(a) or had a
civil judgment for one of those offenses within that time period;
Are presently indicted for or otherwise criminally or civilly charged by a governmental entity (Federal, State,
or local) with commission of any of the offenses listed in 2 CFR 180.800(a); or
Have had one or more public transactions (Federal, State, or local) terminated within the preceding three years
for cause or default.
Disclosure of unfavorable information by grantees under this requirement will not necessarily cause NIH to deny
participation in the grant. NIH will consider the information when determining whether to enter into the covered
transaction. NIH will also consider any additional information or explanation that grantees elect to submit with the
disclosed information. However, if it is later determined that a grantee failed to disclose information that it knew
at the time it accepted the NIH grant award, NIH may (a) terminate the transaction for material failure to comply
with the terms and conditions of the award or (b) pursue any other available remedies, including suspension and
Grantees must immediately report to the NIH funding IC if at any time during the project period, including periods of
no-cost extension, they discover that they (a) failed to disclose information prior to the drawdown of funds or (b)
due to changed circumstances the grantee or any of its principals for the grant now meet the reporting criteria.
"Lower tier" transactions (e.g., consortiums, subcontracts, consultants, collaborators, and contractors
that require the provision of goods or services that will equal or exceed $25,000) also are subject to the HHS
regulations. Prior to entering into a lower tier covered transaction with a participant (as defined in 2
CFR 180.980), grantees must verify that the person (as defined in 2
CFR 180.985) is not excluded or disqualified. Grantees may not enter into any transaction with a person who
is disqualified from that transaction unless an exception under the disqualifying statue, Executive Order, or
regulation has been obtained from HHS.
Grantees must require participants at the next lower tier to (a) comply with the HHS Debarment and Suspension
regulations as a condition of participation in the transaction and (b) pass the requirement to comply with the HHS
Debarment and Suspension regulations to each person involved in the covered transaction at the next lower tier.
Likewise, before entering into such a transaction lower tier participants and contractors under grants (where the
contract requires the provision of goods or services that will equal or exceed $25,000) must report to the grantee
if it or any participants are presently excluded or disqualified.
Grantees also are required to assure compliance for each trainee under a Kirschstein-NRSA institutional research
training grant, or other similar NIH-supported institutional training grant, before their appointment.
Organizations or individuals that are suspended, debarred, or voluntarily excluded from eligibility cannot receive
NIH grants, be paid from NIH grant funds, whether under a primary or lower-tier transaction (including trainees on
NIH-supported training grants), or otherwise participate during the period of suspension, debarment, or exclusion.
Because individuals who have been debarred, suspended, declared ineligible, or voluntarily excluded from covered
transactions may not receive Federal funds for a specified period of time, charges made to the NIH grants for such
individuals (e.g., salary) are unallowable.
4.1.7 Drug-Free Workplace
The Drug-Free Workplace Act of 1988 (41 U.S.C. § 701 et seq.) requires that all organizations receiving grants
from any Federal agency agree to maintain a drug-free workplace. By signing the application, the AOR agrees that the
grantee will provide a drug-free workplace and will comply with the requirement to notify NIH if an employee is
convicted of violating a criminal drug statute. Failure to comply with these requirements may be cause for
debarment. Government wide requirements for Drug-Free Workplace for Financial Assistance are found in 2 CFR
182; HHS implementing regulations are set forth in 2 CFR 382.400. All recipients of NIH grant funds must comply
with the requirements in Subpart B (or Subpart C if the recipient is an individual) of part 382.
4.1.8 Federal Funding Accountability and Transparency Act (FFATA)
Public Law 109-282, the Federal
Funding Accountability and Transparency Act of 2006 as amended (FFATA), requires full disclosure of all entities
and organizations receiving Federal funds including grants, contracts, loans and other assistance and payments
through a single publicly accessible Web site, USASpending.gov. The Web
site includes information on each Federal financial assistance award and contract over $25,000, including such
The name of the entity receiving the award
The amount of the award
Information on the award including FAIN, transaction type, funding agency, etc.
The location of the entity receiving the award
A unique identifier of the entity receiving the award; and
Names and compensation of highly-compensated officers (as applicable)
Compliance with this law is primarily the responsibility of the Federal agency. However, two elements of the law
require information to be collected and reported by recipients: 1) information on executive compensation when not
already reported through the Central Contractor Registry; and 2) similar information on all
subawards/subcontracts/consortiums over $25,000. Information on the recipient reporting requirement for this law can
be found in Monitoring—Reporting—Financial Reports—Recipient
Reporting of Subrecipient Data for FFATA.
This requirement is being implemented in accordance with OMB Interim Final Guidance, Federal Register Volume 75,
Number 177, September 14, 2010. Full text of the award term is available at 2 CFR 170.
4.1.9 Federal Information Security Management Act
All information systems, electronic or hard copy which contain Federal data need to be protected from unauthorized
access. This also applies to information associated with NIH grants and contracts. Congress and the OMB have
instituted laws, policies and directives that govern the creation and implementation of federal information security
practices that pertain specifically to grants and contracts. The current regulations are pursuant to the Federal
Information Security Management Act (FISMA), 44 U.S.C. 3541 et seq. The applicability of FISMA
to NIH grantees applies only when grantees collect, store, process, transmit or use information on behalf of HHS or
any of its component organizations. In all other cases, FISMA is not applicable to recipients of grants, including
cooperative agreements. The grantee retains the original data and intellectual property, and is responsible for the
security of this data, subject to all applicable laws protecting security, privacy, and research. If and when
information collected by a grantee is provided to HHS, responsibility for the protection of the HHS copy of the
information is transferred to HHS and it becomes the agency's responsibility to protect that information and any
derivative copies as required by FISMA.
4.1.10 Financial Conflict of Interest
NIH requires grantees and investigators (except Phase I SBIR/STTR applicants and grantees) to comply with the requirements of 42 CFR 50, Subpart F, "Responsibility of Applicants for Promoting Objectivity in Research for which PHS Funding is Sought." A Final Rule amending the 1995 PHS regulation (and the companion regulation at 45 CFR 94, "Responsible Prospective Contractors," imposing similar requirements for research contracts) was published on August 25, 2011 in the Federal Register (http://www.gpo.gov/fdsys/pkg/FR-2011-08-25/pdf/2011-21633.pdf).
The requirements under the 2011 revised regulation promote objectivity in research by establishing standards that provide a reasonable expectation that the design, conduct, or reporting of research funded under PHS grants or cooperative agreements will be free from bias by any conflicting financial interest of an Investigator, defined as the PD/PI and any other person, regardless of title or position, who is responsible for the design, conduct, or reporting of research funded by PHS, or proposed for such funding, which may include, for example, collaborators or consultants. These requirements do not apply to Federal employees or Federal agencies. Federal agencies have their own set of rules governing financial conflicts of interest for employees. When submitting a grant application, the signature of the AOR certifies the applicant Institution’s compliance with the requirements of 42 CFR 50, Subpart F, including that:
There is in effect at the Institution an up-to-date, written and enforced administrative process to identify and manage Financial Conflicts of Interest (FCOI) with respect to all research projects for which NIH funding is sought or received;
The Institution shall promote and enforce Investigator compliance with the regulation’s requirements including those pertaining to disclosure of Significant Financial Interests;
The Institution shall identify and manage FCOIs and provide initial and ongoing FCOI reports to the NIH consistent with this subpart;
When requested, the Institution will promptly make information available to the NIH/HHS relating to any Investigator disclosure of financial interests and the Institution’s review of, and response to, such disclosure, whether or not the disclosure resulted in the Institution’s determination of an FCOI;
The Institution shall fully comply with the requirements of the regulation.
When the Institution determines that an FCOI exists (see #3 above), the Institution must report to the NIH awarding IC through the submission of an initial and annual FCOI report using the eRA Commons FCOI Module. The initial FCOI report will include the following information:
Grant number and PD/PI or Contact PD/PI if the grant is awarded under the multiple PI model;
Name of Investigator (if different from the PD/PI) with the FCOI;
Name of the entity with which the Investigator has an FCOI;
Nature of the FCOI (e.g., consulting fees, honoraria, paid authorship, equity interest, intellectual property rights and interests, and reimbursed or sponsored travel);
Value of the financial interest $0-4,999; $5,000-9,999; $10,000-19,999; amounts between $20,000-100,000 by increments of $20,000; amounts above $100,000 by increments of $50,000 or a statement that a value cannot be readily determined;
A description how the financial interest relates to the NIH-funded research and the basis for the Institution’s determination that the financial interest conflicts with such research; and
Key elements of the Institution’s management plan, including:
Role and principal duties of the conflicted Investigator in the research project;
Conditions of the management plan;
How the management plan is designed to safeguard objectivity in the research project;
Confirmation of the Investigator’s agreement to the management plan;
How the management plan will be monitored to ensure Investigator compliance; and
Other information as needed.
The annual FCOI report must be submitted to the NIH through the eRA Commons FCOI Module each year within a competitive segment or until the Institution reports that the FCOI no longer exists. The annual FCOI report will include the following information:
Status of the FCOI
Changes to the management plan, if applicable
The Institution will incorporate as part of a written agreement with a subrecipient terms that establish whether the FCOI policy of the awardee Institution or that of the subrecipient will apply to subrecipient Investigators and include time periods to meet disclosure and/or FCOI reporting requirements. Subrecipient Institutions who rely on their FCOI policy must report identified FCOIs to the awardee Institution in sufficient time to allow the awardee Institution to report the FCOI to the NIH to meet its reporting obligations. (See Consortium Agreements, 15.2.1 Written Agreement.)
The Institution will make certain information available concerning identified FCOI held by senior/key personnel as defined in the regulation via a publicly accessible Web site or by a written response to any requestor within five business days of a request, and update such information as specified in the regulation.
The Institution will require each Investigator (including subrecipient Investigators, if applicable) to complete training prior to engaging in NIH-supported research and at least every four years, and immediately under the designated circumstances:
Institutional FCOI policies change in a manner that affects Investigator requirements
An Investigator is new to an Institution
An Institution finds an Investigator noncompliant with the Institution's FCOI policy or management plan.
As described in the regulation, examples of how FCOIs might be addressed include but are not limited to, the following:
Public disclosure of FCOI (e.g., when presenting or publishing the research);
Disclosure of FCOI directly to human subjects research participants;
Monitoring of research by independent reviewer(s);
Modification of the research plan;
Change of personnel or personnel responsibilities, or disqualification of personnel from participation in all or a portion of the research;
Reduction or elimination of Significant Financial Interests (e.g., sale of an equity interest)
Severance of relationships that create financial conflicts.
The information above is only a sample of the regulatory requirements found in 42 CFR 50, Subpart F. Applicants and grantees must review the regulation in its entirety to ensure compliance with all of the requirements. Resources applicable to FCOI, including Frequently Asked Questions, etc. can be found on OER's Conflict of Interest Web site at http://grants.nih.gov/grants/policy/coi/index.htm.
4.1.11 Fly America Act
The Fly America Act (49 U.S.C. 40118) generally provides that foreign air travel funded by Federal government money
may only be conducted on
U.S. flag air carriers. A "U.S. flag air carrier" is an air carrier that holds a certificate under 49 U.S.C.
41102 but does not include a foreign air carrier operating under a permit. There are limited circumstances under
which use of a foreign-flag air carrier is permissible. These circumstances are outlined below:
Airline "Open Skies" Agreements. A foreign flag air carrier may be used if the transportation is
provided under an air transportation agreement between the United States and a foreign government, which the
Department of Transportation has determined meets the requirements of the Fly America Act. For example, in 2008,
the U.S. entered into an "Open Skies" Agreement with the European Union (EU). This Agreement gives European
Community airlines (airlines of Member States) the right to transport passengers and cargo on flights funded by
the U.S. government, when the transportation is between a point in the United States and any point in a Member
State or between any two points outside the United States.
The U.S.-EU Open Skies Agreement was amended effective June 24, 2010. GSA issued Guidance October 6, 2010. Pursuant to the amendment,federal contractors and grantees (not U.S. Government employees) need not be concerned about city-pair contract fares. However, contractors and grantees must check with the airline to ensure that the airline is covered by the U.S.-EU Open Skies agreement which may change periodically.
Additionally, pursuant to the amendment, EU airlines are no longer limited to flying passengers between points in the United States and points in the EU. Instead, EU airlines are authorized to transport passengers between points in the United States and points outside the EU if the EU airline is authorized to serve the route under the U.S.-EU Open Skies Agreement. This includes flights that originate, arrive, or stop in the European Union. For additional information, please see the text of the Amendment and GSA Bulletin FTR 11-02.
information on other "open skies" agreements in which the United States has entered, refer to GSA's
Web site: http://www.gsa.gov/portal/content/103191.
Involuntary Rerouting. Travel on a foreign-flag carrier is permitted if a U.S.-flag air carrier involuntarily
reroutes the traveler via a foreign-flag air carrier, notwithstanding the availability of alternative U.S.-flag
air carrier service.
Travel To and From the U.S. Use of a foreign-flag air carrier is permissible if the airport abroad is: (a) the
traveler's origin or destination airport, and use of U.S.-flag air carrier service would extend the time in a
travel status by at least 24 hours more than travel by a foreign-flag air carrier; or (b) an interchange point,
and use of U.S.-flag air carrier service would increase the number of aircraft changes the traveler must make
outside of the U.S. by two or more, would require the traveler to wait four hours or more to make connections at
that point, or would extend the time in a travel status by at least six hours more than travel by a foreign-flag
Travel Between Points Outside the U.S. Use of a foreign-flag air carrier is permissible if: (a) travel by a
foreign-flag air carrier would eliminate two or more aircraft changes en route; (b) travel by a U.S.-flag air
carrier would require a connecting time of four hours or more at an overseas interchange point; or (c) the
travel is not part of the trip to or from the U.S., and use of a U.S.-flag air carrier would extend the time in
a travel status by at least six hours more than travel by a foreign-flag air carrier.
Short Distance Travel. For all short distance travel, regardless of origin and destination, use of a
foreign-flag air carrier is permissible if the elapsed travel time on a scheduled flight from origin to
destination airport by a foreign-flag air carrier is three hours or less and service by a U.S.-flag air carrier
would double the travel time.
4.1.12 Health and Safety Regulations and Guidelines
Grantees are responsible for meeting applicable Federal, State, and local health and safety standards and for
establishing and implementing necessary measures to minimize their employees' risk of injury or illness in
activities related to NIH grants. In addition to applicable Federal, State, and local laws and regulations, the
following regulations must be followed when developing and implementing health and safety operating procedures and
practices for both personnel and facilities:
Nuclear Regulatory Commission Standards and Regulations, pursuant to the Energy Reorganization Act of 1974 (42
U.S.C. 5801 et seq.). Copies may be obtained from the U.S. Nuclear Regulatory Commission,Washington, DC 20555-0001.
The following guidelines are recommended for use in developing and implementing health and safety operating
procedures and practices for both personnel and facilities:
Prudent Practices for Safety in Laboratories (1995), National Research Council, National Academy Press, 500 Fifth Street, NW, Lockbox 285, Washington, DC 20055 (ISBN 0-309-05229-7). This publication can be obtained by telephoning 800-624-8373. It also is available at http://www.nap.edu/catalog/4911.html.
Grantee organizations are not required to submit documented assurance of their compliance with or implementation of
these regulations and guidelines. However, if requested by the awarding IC, grantees should be able to provide
evidence that applicable Federal, State, and local health and safety standards have been considered and have been
put into practice.
4.1.13 Human Stem Cell Research
Under Executive Order 13505 NIH may support and conduct responsible, scientifically worthy human stem cell research,
including human embryonic stem cell (hESC) research, to the extent permitted by law. NIH Guidelines on Human Stem Cell Research,
effective July 7, 2009, implement the Executive Order. The Guidelines apply to the expenditure of NIH funds for
research using hESCs and certain uses of induced pluripotent stem cells.
For the purpose of the NIH Guidelines, "human embryonic stem cells (hESCs)" are cells that are derived from
the inner cell mass of blastocyst stage human embryos, are capable of dividing without differentiating for a
prolonged period in culture, and are known to develop into cells and tissues of the three primary germ layers.
Although hESCs are derived from embryos, such stem cells are not themselves human embryos. Induced pluripotent stem
cells are human cells that are capable of dividing without differentiating for a prolonged period in culture, and
are known to develop into cells and tissues of the three primary germ layers.
NIH grantees may use hESCs that have been approved by NIH in accord with the NIH Guidelines and are posted on the NIH Human Embryonic Stem Cell Registry, or may
establish eligibility of specific cell lines for NIH funding by submitting a Request for Human Embryonic Stem Cell Line to be
Approved for Use in NIH Funded Research (NIH Form 2890). Prior to the use of NIH funds, applicants and
grantees must provide assurances, when endorsing applications and progress reports submitted to NIH for projects
using hESCs, that the hESCs to be used are listed on the NIH Registry and will be used in accordance with any
restrictions associated with the line as cited on the Registry. If a specific line from the NIH Registry cannot be
identified at the time of submission, the applicant/grantee must provide a strong justification why one cannot be identified at that time and a certification that one from the NIH Registry
will be used.
DHHS regulations for Protection of Human Subjects, 45 CFR 46, Subpart A, establish safeguards
for individuals who are the sources of many human tissues used in research, including non-embryonic human adult stem
cells and human induced pluripotent stem cells. When research involving human adult stem cells or induced
pluripotent stem cells constitutes human subject research, Institutional Review Board review may be required and
informed consent may need to be obtained per the requirements detailed in 45 CFR 46, Subpart A.
In addition, 45 CFR 46, Subpart A, may apply to certain research using hESCs. This regulation applies, among other
things, to research involving individually identifiable private information about a living individual, 45 CFR 46.102(f).
The HHS Office for Human Research Protections (OHRP) considers biological
material, such as cells derived from human embryos, to be individually identifiable when they can be linked to
specific living individuals by the investigators either directly or indirectly through coding systems. Thus, in
certain circumstances, IRB review may be required, in addition to compliance with these Guidelines. Applicant
institutions are urged to consult OHRP guidance at http://www.hhs.gov/ohrp/policy/index.html#topics.
220.127.116.11 hESC Research Prohibited with NIH Funding
The following uses of hESCs, even if derived from embryos donated in accordance with the NIH Guidelines and listed on
the NIH Registry or human induced pluripotent stem cells, are prohibited:
Research in which hESCs or human induced pluripotent stem cells are introduced into non-human primate
Research involving the breeding of animals where the introduction of hESCs or human induced pluripotent stem
cells may contribute to the germ line.
In addition, the derivation of stem cells from human embryos is prohibited in NIH funded research by the annual
appropriations ban on funding of human embryo research known as the Dickey Wicker Amendment. NIH funding for
research using hESCs derived from other sources, including somatic cell nuclear transfer, parthenogenesis, and/or
IVF embryos created for research purposes, is also prohibited.
4.1.14 Human Fetal Tissue Research
Human fetal tissue is defined as tissue or cells obtained from a dead human embryo or fetus after a spontaneous or
induced abortion or stillbirth. This definition does not include established human fetal cell lines. Research
involving the transplantation of human fetal tissue must be conducted in accordance with applicable Federal, State
and local laws as well as the following NIH guidance.
Guidance for grantees conducting research on human fetal tissue and other information on the governing Federal
statute is found in sections 498A and 498B of the PHS Act, 42 U.S.C. 298g-2.
The scientific and ethical challenges associated with research utilizing human fetal tissue make it imperative that
researchers and their organizations be fully aware of and in compliance with the Federal requirements, particularly
section 498B. When an application involving human fetal tissue research is submitted to NIH, the AOR's signature
certifies that researchers using these tissues are in compliance with section 498B of the PHS Act. The statute
specifically prohibits any person from knowingly acquiring, receiving, or transferring any human fetal tissue for
valuable consideration. The term "valuable consideration" is a concept similar to profit and does not
include reasonable payment for costs associated with the collection, processing, preservation, storage, quality
control, or transportation of these tissues. Violation of this statute carries criminal penalties that apply to both
those that supply and those that acquire human fetal tissue.
18.104.22.168 Research on Transplantation of Human Fetal Tissue
Sections 498A and 498B contain additional requirements for research on the transplantation of human fetal
tissue for therapeutic purposes conducted or supported by NIH. Under section 498A, the official who signs the
application is certifying that the research on transplantation of human fetal tissue will adhere to the following
The woman who donates the fetal tissue must sign a statement declaring that the donation is being made:
for therapeutic transplantation research,
without any restriction regarding the identity of individuals who may receive the transplantation, and
without the donor knowing the identity of the recipient.
The attending physician must sign a statement that he/she has:
obtained the tissue in accordance with the donor's signed statement and
fully disclosed to the donor his or her intent, if any, to use the tissue in research and any known
medical risks to the donor or risks to her privacy associated with the donation that are in addition to
risks associated with the woman's medical care.
In the case of tissue obtained pursuant to an induced abortion, the physician's statement also must state that
obtained the woman's consent for the abortion before requesting or obtaining consent for the tissue to
did not alter the timing, method, or procedures used to terminate the pregnancy solely for the purpose
of obtaining the tissue for research; and
performed the abortion in accordance with applicable State and local laws.
The PD/PI must sign a statement certifying that he/she is aware that the tissue is human fetal tissue obtained
in a spontaneous or induced abortion, or pursuant to a stillbirth and that the tissue was donated for research
purposes. The PD/PI also must certify that this information has been shared with others who have
responsibilities regarding the research and, before eliciting informed consent from the transplantation
recipient, will obtain written acknowledgment that the patient is aware of the aforementioned information.
The PD/PI must certify in writing that he/she has had no part in any decisions as to the timing, method, or
procedures used to terminate the pregnancy.
In submitting an application to NIH, the AOR that signs the application is certifying that, if research on the
transplantation of human fetal tissue is conducted under the grant-supported project, the organization will make
available for audit by the HHS Secretary or designee, the physician statements, the PD/PI's statements, and informed
consents required by subsections 498A(b)(2) and (c) of the PHS Act or will ensure HHS access to those records, if
maintained by an entity other than the grantee. This requirement is in addition to the requirements concerning human
subjects in research.
In addition, FDA has jurisdiction over fetal cells and tissues intended for use in humans and requests that
investigators contact them to determine whether any planned or ongoing clinical research would require submission of
IND application. Additional information and FDA contact information is available at http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/ucm105857.htm.
4.1.15 Human Subjects Protections
The HHS regulations for the protection of human subjects, in 45 CFR 46, implement Section 491(a) of the PHS Act
and provide a framework, based on established, internationally recognized ethical principles, to safeguard the
rights and welfare of individuals who participate as subjects in research activities supported or conducted by the
NIH or other HHS components.
The HHS regulations stipulate that the grantee organization(s), whether domestic or foreign, bears ultimate
responsibility for safeguarding the rights and welfare of human subjects in HHS-supported activities (46.101(a) and
46.103(a)). Grantee institutions "engaged" in human subjects research must obtain a Federalwide Assurance
(FWA) with the HHS Office for Human Research Protections (OHRP), and establish appropriate policies and procedures
for the protection of human subjects. An institution is engaged in human subjects research if:
the institution's employees or agents intervene or interact with human subjects for research purposes;
the institution's employees or agents obtain individually identifiable private information about human subjects
for research purposes; or
the institution receives a direct HHS award to conduct human subjects research, even where all activities
involving human subjects are carried out by a subcontractor or collaborator.
The HHS regulations at Subparts B, C, and D include additional protections for specific populations as follows:
human fetuses, pregnant women, and neonates (45 CFR 46, Subpart B);
prisoners (45 CFR 46, Subpart C); and
children (45 CFR 46, Subpart D).
Certain research activities are exempt from regulatory requirements for an FWA and IRB oversight (45 CFR 46.101(b)).
OHRP guidance states that institutions
must adopt clear procedures under which the IRB (or some authority other than the investigator) determines whether
proposed research is exempt from the human subjects regulations. NIH will make a final determination as to whether
proposed activities are covered by the regulations or are in an exempt category, based on the information provided
in the Research Plan.
Unless all research activities meet the criteria for one or more exemptions from 45 CFR 46, research involving human
subjects may only be conducted under an HHS award if the organization has a current OHRP approved FWA and provides
certification that an Institutional Review Board (IRB) registered under the specific Assurance has reviewed and
approved the proposed activity in accordance with the HHS regulations.
In accepting an award that supports human subjects research, the grantee institution assumes responsibility for all
research conducted under the award, including protection of human subjects at all participating and consortium
sites, and for ensuring that an FWA and certification of IRB review and approval exists for each site before human
subjects research may begin. When consultants are performing research involving human subjects on NIH-funded
projects, the consultant's institution must establish an approved FWA.
The NIH Office of Extramural Research Human Subjects Web site contains additional information and Frequently Asked
Questions that are available to help investigators understand how these Federal requirements apply to their
research. See http://grants.nih.gov/grants/policy/hs/index.htm.
Applications will be considered incomplete if they do not address the involvement of human subjects in the Research
Plan of the application. If human subjects research is anticipated within the period of the award but definite plans for
involvement of human subjects cannot be described in the application (referred to as "delayed onset human subjects research" in the NIH grant application instructions), applicants must provide a detailed explanation
of why it is not possible to develop definite plans. Prior to the involvement of human subjects the grantee must submit
to the NIH awarding IC for prior approval either (1) detailed information as required in the Research Plan of the
application, and meet the FWA and IRB certification requirements, or (2) if all of the research meets the criteria
for one or more exemptions, identification of which exemptions(s) is/are applicable to the research, and a
justification for the exemption with sufficient information about the involvement of human subjects to allow a
determination that the claimed exemption is appropriate. Typically, grantees that are part of large clinical research networks or consortia that plan to add new protocols after the award must follow the awarding IC's procedures for approval of new protocols. Institutions with award mechanisms that allow them to select new projects, typically small future research projects (e.g., pilot projects), for support by their NIH award are responsible for ensuring that the selected projects follow all relevant regulations and policies including those governing the involvement of human subjects in research, including prior approval from the institutional IRB if applicable. They must follow the awarding IC's procedures for prior approval of new protocols and updating the IC on the status of funded projects in annual progress reports which are typically described in the FOA and/or NoA.
Grantees may not draw funds from the payment system, request funds from the paying office, or make obligations
against Federal funds for research involving human subjects at any site engaged in nonexempt research for any period
not covered by both an FWA and IRB approval consistent with 45 CFR 46. Costs associated with IRB review of
human research protocols are not allowable as direct charges to NIH-funded research unless such costs are not
covered by the organization's F&A rate.
The use of autopsy materials is governed by applicable State and local law and is not directly regulated by 45 CFR 46.
22.214.171.124 Federalwide Assurance Requirements
The Federalwide Assurance (FWA) commits the institution to compliance with the requirements set forth in 45 CFR 46,
and the Terms of Assurance. Each institution that is "engaged" in HHS supported human subjects research
must obtain an FWA from OHRP. (See http://www.hhs.gov/ohrp/assurances/assurances/index.html.)
When an applicant organization proposes non-exempt human subjects research and does not have a FWA, the AOR signature
on the application constitutes declaration that the organization will comply with 45 CFR 46 and proceed to obtain a
FWA. The NIH awarding component will place a restriction in the NoA so that no human subjects research may be
conducted under the award until the FWA and certification of IRB review and approval (or certification of institutional determination of exemption, if applicable) have been obtained and accepted
Each legally separate entity must file its own FWA even if the organization does not operate its own IRB and
designates another IRB (registered with OHRP and agreeing to the designation) for that purpose. Affiliated
organizations or organizations that will serve as additional performance sites for the grant-supported research also
must file an FWA. It is the grantee organization's responsibility to ensure that all sites engaged in research
involving human subjects have an appropriate FWA and IRB approval consistent with 45 CFR 46. It also is the
grantee's responsibility to comply with NIH prior approval requirements related to the addition of sites not
included in the approved application (see Administrative
Requirements—Changes in Project and Budget—Prior Approval Requirements). A list of organizations
with approved assurances is available at the OHRP Web site (http://www.hhs.gov/ohrp).
No individual may receive NIH grant funds for nonexempt research involving human subjects unless the individual is
affiliated with or sponsored by an organization that assumes responsibility for the research under an FWA or the
individual makes other arrangements with OHRP.
Detailed information concerning FWAs, including the OHRP Assurance Training Module, is available on the OHRP Web site
126.96.36.199 Certification of IRB Approval
Grantees must provide a certification to NIH that the research application has been approved by an appropriate IRB,
consistent with 45 CFR 46. IRB approval must have been granted within 12 months before the budget period start date
to be valid.
Certification of IRB approval may be filed at any time before award in accord with Just-in-Time procedures, unless
required earlier by the IC. Therefore, following peer review and notification of impact score/percentile,
applicant organizations with OHRP FWAs may wish to proceed with IRB review for those applications that have not yet
received IRB approval and that appear to be in a fundable range.
The HHS regulations require that the IRB review the actual application or proposal for HHS support (45 CFR 46.203(f)). OHRP's 5/31/2000 memo IRB Review of Applications for HHS Support (http://www.hhs.gov/ohrp/policy/aplrev.html) recommends
that IRBs ensure that all research described in the application or proposal is entirely consistent with any
corresponding protocol(s) submitted to the IRB.
188.8.131.52 Reporting to Funding Agency and OHRP
Under the HHS regulations, grantee institutions must have written procedures for ensuring prompt reporting to the
IRB, appropriate institutional officials, and the NIH of any unanticipated problem involving risks to subjects or
others or any serious or continuing noncompliance with 45 CFR 46 or IRB requirements (45 CFR 46.103(b)(5)). Any IRB suspension or termination of approval must include a statement of the reasons
for the IRB's action and must be reported promptly to the investigator, appropriate institutional officials, and NIH (45 CFR 46.113). Grantee institutions must also file incident reports with OHRP
of unanticipated problems involving risks to subjects or others, serious or continuing noncompliance with 45 CFR 46
or with the requirements or determinations of the IRB, and suspension or termination of IRB approval. See OHRP
6/20/20011 Guidance on Reporting Incidents to OHRP (http://www.hhs.gov/ohrp/compliance/reports/index.html).
184.108.40.206 OHRP Oversight
OHRP has regulatory responsibility for oversight of grantee compliance with the HHS human subjects regulations. In
carrying out this responsibility, OHRP evaluates all written allegations or indications of non-compliance with the
HHS regulations it receives from any source. All compliance oversight evaluations are predicated on the HHS
regulations and the organization's assurance of compliance. Any corrective actions imposed as a result of a compliance
oversight evaluations are intended to remedy identified non-compliance and prevent reoccurrence. Because each case
is different, OHRP tailors corrective actions to foster the best interest of human research subjects and, to the
extent possible, of the organization, research community, and HHS. Most compliance oversight evaluations and
resultant corrective actions are resolved at the OHRP level. However, OHRP may recommend actions to be taken by
other HHS officials.
Information about the FWA submission process and about OHRP activities related to oversight and compliance, as well
as copies of the human subjects regulations, may be obtained from OHRP at the address shown in Part III or from its
home page at http://www.hhs.gov/ohrp/.
220.127.116.11 Education in the Protection of Human Research Participants
Before funds are awarded for competing applications involving human subjects, applicants must submit documentation
that all senior/key personnel involved in human subjects research have received training
in the protection of human subjects. Senior/key personnel include all individuals responsible for the design or
conduct of the study, including senior/key personnel of consortium participants or alternate performance sites if
they are participating in research that involves human subjects. This documentation should be included in the cover
letter signed by the AOR that accompanies the description of other support, IRB and IACUC approval, and other
information submitted prior to funding in accordance with Just-in-Time procedures. For non-competing continuation
awards, the description of education for new senior/key personnel should be part of the progress report submitted as
a prerequisite to award. A free, web-based tutorial that presents information about protections for human
participants in research, and satisfies the NIH human subjects training requirement, is found at http://phrp.nihtraining.com/. Additional information about this
education requirement is available on the NIH Web site at: http://grants.nih.gov/grants/policy/hs_educ_faq.htm.
18.104.22.168 Data and Safety Monitoring
The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported
human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the
validity and integrity of the data. The NIH policies on data and safety monitoring specify that the level and
frequency of monitoring should be commensurate with the risks, nature, and complexity of the clinical trial, and are
in addition to any monitoring requirements imposed by FDA or the NIH Guidelines for Research Involving
Recombinant DNA Molecules ("NIH Guidelines"). There are a number of options for monitoring clinical trials including, but
not limited to, monitoring by a/an:
Independent individual/safety officer,
Designated medical monitor,
Internal committee or board with explicit guidelines,
DSMB (required for multi-site trials).
Applications that include clinical trials must include a general description of the data and safety monitoring plan.
The description of the data and safety monitoring plan in competing applications will be reviewed by the SRG. A
general description of a monitoring plan establishes the overall framework for data and safety monitoring. It must
describe the entity that will be responsible for monitoring how adverse events will be reported to the IRB and the
NIH and, when appropriate, how the NIH Guidelines and FDA regulations for INDs and IDEs will be satisfied.
A detailed monitoring plan must be included as part of the research protocol, be submitted to the local IRB, and be
reviewed and approved by the NIH awarding IC prior to the accrual of human subjects. The awarding IC may specify the
reporting requirements for adverse events, which are in addition to the annual report to the IRB. The clinical trial
monitoring function is above and beyond that traditionally provided by IRBs; however, the IRB must be cognizant of
the procedures used by clinical trial monitoring entities and the monitor must provide periodic reports to
investigators for transmittal to the local IRB.
NIH specifically requires the establishment of DSMBs for multi-site clinical trials involving interventions that
entail potential risk to the participants, and generally for Phase III clinical trials. Although Phase I and Phase
II clinical trials also may use DSMBs, smaller clinical trials may not require this oversight format, and
alternative monitoring plans may be appropriate.
For multi-site Phase I and II trials, investigators should organize a central reporting entity that will be
responsible for preparing timely summary reports of adverse events for distribution among sites and the IRBs of
participating sites. The frequency of summary reports will depend on the nature of the trial. Organizations with a
large number of clinical trials may develop standard monitoring plans for Phase I and II clinical trials. However,
such plans always should be evaluated for appropriateness for the particular investigation.
All multi-site trials with DSMBs are expected to forward summary reports of adverse events to individual IRBs so they
can address reports related to the site for which they have responsibility. Grantees should address questions on
this subject to the NIH PO.
22.214.171.124 Inclusion of Children as Subjects in Clinical Research
NIH-conducted or supported clinical research must adhere to the NIH Policy and Guidelines on the Inclusion of
Children as Participants in Research Involving Human Subjects. The goal of the Policy is to increase the
participation of children in research so that adequate data will be developed to support the cause, treatment and
cure of diseases that affect children (http://grants.nih.gov/grants/funding/children/children.htm).
NIH supported clinical research must include children in the research design unless there are scientific or ethical
reasons not to include them. For the purpose of this policy requirement a child is defined as an individual under
the age of 21 years.
The involvement of children in clinical research must be in compliance with all applicable provisions of pertinent
Federal laws and regulations, including the HHS human subjects regulations at 45 CFR 46 Subpart D, which
address additional protections for children who participate as subjects in research.
Investigative teams are to have expertise in dealing with children of the ages included as subjects, facilities to
must be appropriate to accommodate the children, and there must be inclusion of a sufficient number of children to
contribute to a meaningful analysis relative to the purpose of the study.
126.96.36.199 Inclusion of Women and Minorities as Subjects
in Clinical Research and Reporting Sex/Gender, Racial, and Ethnic Participation
NIH-conducted and –supported Clinical research must conform to the NIH Policy and Guidelines on the
Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm),
in accord with Public Health Service Act sec. 492B, 42 U.S.C. sec 289a-2. The policy requires that
women and members of minority groups and their subpopulations be included in NIH-conducted or supported clinical
research, unless a clear and compelling rationale and justification establishes to the satisfaction of the NIH IC
Director that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research.
Exclusion under other circumstances may be made by the Director, NIH, upon the recommendation of an IC Director
based on a compelling rationale and justification.
Cost is not an acceptable reason for exclusion except when the research would duplicate existing data. Women of
childbearing potential should not be routinely excluded from participation in clinical research. The policy applies
to research subjects of all ages in NIH-supported clinical research studies (see definition of clinical research).
The inclusion of individuals on the basis of sex/gender, race, and ethnicity must be addressed in developing a
research design appropriate to the scientific objectives of the study. A proposed outreach program for recruiting
should also be included. When an NIH-defined Phase III clinical trial is
proposed, investigators must consider whether clinically important sex/gender, racial, and/or ethnic differences in the
intervention effect are to be expected and plan the research accordingly.
Investigators must also collect and annually report information on sex/gender, race, and ethnicity in clinical
research studies. The OMB minimum standards for maintaining, collecting, and presenting data on race and ethnicity
for all grant projects are described in OMB Directive
No. 15. The categories in this classification are social-political constructs and should not be interpreted
as being scientific or anthropological in nature. The standards include five racial categories: American Indian or
Alaska Native, Asian, Black or African American, Native Hawaiian or Other Pacific Islander, and White. There are two
categories for ethnicity: "Hispanic or Latino," and "Not Hispanic or Latino."
4.1.16 Investigational New Drug
Applications/Investigational Device Exceptions
To be eligible for NIH funding, all clinical research involving investigational drugs and devices, or other products
regulated by the FDA, must comply with all applicable FDA requirements, including those for INDs, IDEs, and human
subjects protections. Among other provisions, FDA regulations for human subjects protections are published in 21 CFR
parts 50 and 56 with additional standards found in parts 312 and 812.
When applicable, the sponsor of the IND/IDE, whether NIH, a grantee, or a third party, is legally responsible for
meeting the FDA requirements for sponsors. If the sponsor is also the PI, then the sponsor will need to satisfy
FDA's requirements for sponsor-investigators. If the IND/IDE sponsor is a third party, such as a pharmaceutical
company or research organization under contract to a grantee or to a pharmaceutical company, the legal
responsibility for monitoring the clinical trial and reporting to FDA rests with the sponsor rather than the
grantee. This generally will be the case for larger, multi-site clinical trials. If the grantee is the IND/IDE
holder, commonly referred to as an "investigator-initiated IND/IDE," the grantee or the investigator
serves as the sponsor and assumes the legal responsibility. In any case, the grantee is ultimately responsible to
NIH for ensuring compliance with the applicable requirements for protection of human subjects, including compliance
with FDA's requirements.
Following the filing of an
IND, FDA has a 30-day period in which to review it. FDA may allow the
IND to proceed or may defer approval of the
IND until changes it deems acceptable are made. FDA also may order a clinical trial to be suspended or terminated,
at any time, based on information it receives about that clinical trial.
When NIH funds any part of a clinical study involving an
IND or an IDE, NIH must be knowledgeable about any significant communications with FDA concerning the study. The
grantee organization must report certain types of FDA communications to the NIH awarding IC within 72 hours of
receiving a copy of, or upon being informed of, the FDA communication (through the PD/PI or another person acting on
behalf of the grantee), whichever occurs first. This notification requirement applies to any of the following
communications from FDA with the sponsor of the
IND or IDE:
Warning letters (whether sent to the grantee or to the commercial sponsor)
Notices of Initiation of Disqualification Proceedings and
Opportunity to Explain
Opportunity for Hearing
Notice of Disqualification
Clinical hold letters that pertain to breaches of good manufacturing practices, good clinical practices, or
other major issue requiring significant changes in the protocol.
The notification should be made in writing, but also may be done by telephone if a written notice would delay the
notification. It should include a statement of the action taken or contemplated and the assistance needed to resolve
the situation. These requirements apply to the grantee even if the grantee or the NIH-funded PD/PI is the sponsor.
Failure to comply with this requirement may result in NIH imposing a corrective and/or enforcement action (see Administrative Requirements—Enforcement Actions). FDA
communications are considered grant-related records for purposes of retention and access (see Administrative Requirements—Monitoring—Record
Retention and Access).
4.1.17 Lobbying Prohibition
Recipients of Federal grants, cooperative agreements, contracts, and loans are prohibited by 31 U.S.C. 1352, "Limitation
on use of appropriated funds to influence certain Federal contracting and financial transactions," from using
appropriated Federal funds to pay any person for influencing or attempting to influence any officer or employee of
an agency, a Member of Congress, an officer or employee of Congress, or an employee of a Member of Congress with
respect to the award, continuation, renewal, amendment, or modification of any of these instruments. These
requirements are implemented for HHS in 45 CFR 93, which also describes types of activities, such as
legislative liaison activities and professional and technical services, which are not subject to this
prohibition under certain circumstances.
Applicants for NIH awards are required to certify and disclose that they:
have not made, and will not make, such a prohibited payment;
used or will use non-appropriated funds if they have made or agreed to make such payment; and
will include these requirements in consortium agreements and contracts under grants that will exceed $100,000
and obtain necessary certifications from those consortium participants and contractors.
Certifications and disclosures must be filed at the times prescribed in the regulations based on the expected total costs.
Consistent with EO 12770 (July 25, 1991), Metric Usage in Federal Government Programs, measurement values in
applications and grantee-prepared reports, publications, and other grant-related documents should be in metric. See
Construction Grants chapter in IIB for requirements for metric
usage in construction activities.
4.1.19 Military Recruiting and Reserve Officer
Training Corps Program Access to Institutions of Higher Education
Section 588 of the National Defense Authorization Act of 1995, amended (10 U.S.C. § 983), precludes NIH grant
awards to institutions of higher education that DoD determines have an anti-Reserve Officer Training Corps (ROTC)
policy or practice (regardless of when implemented) that either prohibits or, in effect, prevents the Secretary of
Defense from gaining entry to campuses or access to students or information for military recruiting. DoD publishes
each determination of ineligibility in the Federal Register as well as publishing, once every 6 months,
a list of all currently ineligible schools. If DoD determines that an institution is ineligible during an ongoing
project period, NIH will suspend support of current and future grant awards as provided in Administrative Requirements—Enforcement Actions—Suspension,
Termination, and Withholding of Support. Funding eligibility may be restored on the basis of new information
provided by DoD.
4.1.20 National Environmental Policy Act
All NIH grants, whether or not they include construction or major A&R activities, are subject to the requirements
of the National Environmental Policy Act (NEPA) of 1969, as amended. This Act requires Federal agencies to consider
the reasonably foreseeable environmental consequences of all grant-supported activities. As part of NIH's
implementation of this Act, grantees are required to promptly notify NIH of any reasonably foreseeable impacts on
the environment from grant-supported activities, or certify that no such impacts will arise upon receipt of a grant
award. In addition, NIH has determined that most NIH research grants are not expected to individually or
cumulatively have a significant effect on the environment unless any part of the proposed research and/or project
includes one or more of the following categorical exclusions listed below:
The potential environmental impacts of the proposed research may be of greater scope or size than other actions
included within a category.
The proposed research threatens to violate a Federal, State, or local law established for the protection of the
environment or for public health and safety.
Potential effects of the proposed research are unique or highly uncertain.
Use of especially hazardous substances or processes is proposed for which adequate and accepted controls and
safeguards are unknown or not available.
The proposed research may overload existing waste treatment plants due to new loads (volume, chemicals,
toxicity, additional hazardous wasted, etc.).
The proposed research may have a possible impact on endangered or threatened species.
The proposed research may introduce new sources of hazardous/toxic wastes or require storage of wastes pending
new technology for safe disposal.
The proposed research may introduce new sources of radiation or radioactive materials.
Substantial and reasonable controversy exists about the environmental effects of the proposed research.
The Federal Debt Collection Procedures Act of 1990 (Act), 28 U.S.C. 3201(e), provides that an organization or
individual that is indebted to the United States , and has a judgment lien filed against it, is ineligible to
receive a Federal grant. NIH cannot award a grant unless the AOR of the applicant organization (or individual in the
case of a Kirschstein-NRSA individual fellowship) certifies, by means of his/her signature on the application, that
the organization (or individual) is not delinquent in repaying any Federal debt. If the applicant discloses
delinquency on a debt owed to the Federal government, NIH may not award the grant until the debt is satisfied or
satisfactory arrangements are made with the agency to which the debt is owed. In addition, once the debt is repaid
or satisfactory arrangements made, NIH will take that delinquency into account when determining whether the
applicant would be a responsible NIH grant recipient.
Anyone who has been judged to be in default on a Federal debt and who has had a judgment lien filed against him or
her should not be listed as a participant in an application for an NIH grant until the judgment is paid in full or
is otherwise satisfied. No funds may be used for or rebudgeted following an award to pay such an individual. NIH
will disallow costs charged to awards that provide funds to individuals in violation of this Act.
These requirements apply to all types of organizations and awards, including foreign grants.
4.1.22 President's Emergency Plan for AIDS Relief (PEPFAR) Program
188.8.131.52 PEPFAR Agreements
Special terms and conditions concerning prostitution and sex trafficking apply to all grants awarded under the U.S. President's Emergency Plan for AIDs Relief (PEPFAR) program. These are:
The U.S. Government is opposed to prostitution and related activities, which are inherently harmful and dehumanizing, and contribute to the phenomenon of trafficking in persons. None of the funds made available under this agreement may be used to promote or advocate the legalization or practice of prostitution or sex trafficking. Nothing in the preceding sentence shall be construed to preclude the provision to individuals of palliative care, treatment, or post-exposure pharmaceutical prophylaxis, and necessary pharmaceuticals and commodities, including test kits, condoms, and, when proven effective, microbicides.
The following definitions apply for purposes of this provision:
"Commercial sex act" means any sex act on account of which anything of value is given to or received by any person.
"Prostitution" means procuring or providing any commercial sex act and the “practice of prostitution” has the same meaning.
means the recruitment, harboring, transportation, provision, or obtaining of a person for the purpose of a commercial sex act.
The Grantee must insert this provision, which is a standard provision, in all subawards or subcontracts.
This provision includes express terms and conditions of the award and any violation of it is grounds for unilateral termination of the award by NIH prior to the end of its term.
184.108.40.206 PEPFAR Agreements Between the U.S. Government and Foreign Non-Governmental Organizations (NGOs)
Additional requirements regarding the opposition to prostitution and sex trafficking apply to grants awarded under PEPFAR and issued to foreign Non-Governmental Organizations (NGOs). The terms and conditions for such agreements with foreign NGOs are:
The U.S. Government is opposed to prostitution and related activities, which are inherently harmful and dehumanizing, and contribute to the phenomenon of trafficking in persons. None of the funds made available under this agreement may be used to promote or advocate the legalization or practice of prostitution or sex trafficking. Nothing in the preceding sentence shall be construed to preclude the provision to individuals of palliative care, treatment, or post-exposure pharmaceutical prophylaxis, and necessary pharmaceuticals and commodities, including test kits, condoms, and, when proven effective, microbicides.
Except as provided in (b)(2) and (b)(3), by accepting this award or any subaward, a non-governmental organization or public international organization awardee/subawardee agrees that it is opposed to the practices of prostitution and sex trafficking because of the psychological and physical risks they pose for women, men, and children. Any enforcement of this clause is subject to Alliance for Open Society International v. USAID, 05 Civ. 8209 (S.D.N.Y., orders filed on June 29, 2006 and August 8, 2008) (orders granting preliminary injunction) for the term of the Orders.
The following organizations are exempt from (b)(1): the Global Fund to Fight AIDS, Tuberculosis and Malaria; the World Health Organization; the International AIDS Vaccine Initiative; and any United Nations agency.
Contractors and subcontractors are exempt from (b)(1) if the contract or subcontract is for commercial items and services as defined in FAR 2.101, such as pharmaceuticals, medical supplies, logistics support, data management, and freight forwarding.
Notwithstanding section (b)(3), not exempt from (b)(1) are recipients, subrecipients, contractors, and subcontractors that implement HIV/AIDS programs under this assistance award, any subaward, or procurement contract or subcontract by:
Providing supplies or services directly to the final populations receiving such supplies or services in host countries;
Providing technical assistance and training directly to host country individuals or entities on the provision of supplies or services to the final populations receiving such supplies and services; or
Providing the types of services listed in FAR 37.203(b)(1)-(6) that involve giving advice about substantive policies of a recipient, giving advice regarding the activities referenced in (i) and (ii), or making decisions or functioning in a recipient's chain of command (e.g., providing managerial or supervisory services approving financial transactions, personnel actions).
The following definitions apply for purposes of this provision:
"Commercial sex act" means any sex act on account of which anything of value is given to or received by any person.
"Prostitution" means procuring or providing any commercial sex act and the “practice of prostitution” has the same meaning.
"Sex trafficking" means the recruitment, harboring, transportation, provision, or obtaining of a person for the purpose of a commercial sex act. 22 U.S.C. 7102(9).
The recipient shall insert this provision, which is a standard provision, in all subawards, procurement contracts or subcontracts.
This provision includes express terms and conditions of the award and any violation of it shall be grounds for unilateral termination of the award by NIH prior to the end of its term.
4.1.23 Pro-Children Act of 1994
Public Law 103-227, Title X, Part C, Environmental Tobacco Smoke, also known as the Pro-Children Act of 1994, imposes
restrictions on smoking in facilities where federally funded children's services are provided. NIH grants are
subject to these requirements only if they meet the Act's specified coverage. The Act specifies that smoking is
prohibited in any indoor facility (owned, leased, or contracted for) used for the routine or regular provision of
kindergarten, elementary, or secondary education or library services to children under the age of 18. In addition,
smoking is prohibited in any indoor facility or portion of a facility (owned, leased, or contracted for) used for
the routine or regular provision of federally funded health care, day care, or early childhood development (Head
Start) services to children under the age of 18. The statutory prohibition also applies if such facilities are
constructed, operated, or maintained with Federal funds. The statute does not apply to children's services provided
in private residences, facilities funded solely by Medicare or Medicaid funds, portions of facilities used for
inpatient drug or alcohol treatment, or facilities where Women, Infants and Children (WIC) coupons are redeemed.
Failure to comply with the provisions of the law may result in the imposition of a civil monetary penalty of up to
$1,000 per violation and/or the imposition of an administrative compliance order on the responsible entity.
Because of the nature of NIH programs and funding, individual transactions, rather than entire programs, may be
subject to these requirements. The signature of the AOR will indicate the intent to comply. Any questions concerning
the applicability of these provisions to an NIH grant should be directed to the GMO.
220.127.116.11 Public Health Security and Bioterrorism
Preparedness and Response Act (Select Agents)
The Public Health Security and Bioterrorism Preparedness and Response Act of 2002, 42 U.S.C. 201, is designed to
provide protection against misuse of select agents and toxins whether inadvertent or the result of terrorist acts
against the U.S. homeland or other criminal acts. The Act was implemented, in part, through regulations published by
HHS and USDA at 42 CFR 73, 9 CFR 121 and 7 CFR 331 or commonly referred to as "Select Agent Regulations."
Copies of these regulations are available at http://www.selectagents.gov/Regulations.html,
or can be obtained from CDC,
1600 Clifton Road,
30333; telephone: 404-718-2000.
Research involving select agents and recombinant or synthetic nucleic acid molecules also is subject to the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines). The NIH Guidelines apply to all research projects (NIH-funded and non-NIH-funded) that involve recombinant or synthetic nucleic acid molecules and are conducted at or sponsored by an organization that receives NIH support for recombinant or synthetic nucleic acid molecule research. A copy of the NIH Guidelines are available at http://oba.od.nih.gov/oba/index.html.
18.104.22.168.1 Select Agents
22.214.171.124.1.1 Select Agent Awards to U.S. Institutions
Domestic grantees who conduct research involving select agents or toxins (see Section 3 and 4 of 42 CFR 73 and 9 CFR 121 and Section 3 of 7 CFR 331) must maintain a registration with CDC (or USDA, depending on the agent) before using
NIH funds. No funds can be used for research involving select agents or toxins if the registration certificate
maintained by CDC or USDA is suspended or revoked.
126.96.36.199.1.2 Select Agent Awards to Foreign Institutions and International Organizations
Foreign Institutions and International Organizations who conduct research involving select agents (see 42 CFR 73 for
the select agent list; and 7 CFR 331 and 9 CFR 121 for the relevant animal and plant pathogens) must provide
information satisfactory to the NIH that a process equivalent to that described in 42 CFR 73 for U.S. institutions
is in place and will be administered on behalf of all select agent work sponsored by NIH funds before using these
funds for any work directly involving select agents. Grantees must be willing to address the following key elements
appropriate for their institutions: safety, security, training, procedures for ensuring that only
approved/appropriate individuals have access to the select agents, and any applicable laws, regulations and policies
equivalent to 42 CFR 73. If this work will not, in fact, involve select agents (e.g. excluded strains), and you
provide documentation satisfactory to the NIH that your work does not now nor will it in the future (i.e. throughout
the life of the award) involve select agents, no further action will be necessary.
188.8.131.52.1.3 Select Agent Awards to U.S. Institutions with Foreign Subcomponents
Grantees who conduct research involving select agents (see 42 CFR 73 for the select agent list; and 7 CFR 331 and 9
CFR 121 for the relevant animal and plant pathogens) must complete registration with CDC (or USDA, depending on the
agent) before using NIH funds for any work directly involving the select agent at the U.S. institution. No funds can
be used for research involving select agents if the final registration certificate is denied. Before using NIH funds
for any work directly involving the select agents at a foreign subrecipient, the U.S. grantee must provide
information from the foreign institution satisfactory to the NIH that a process equivalent to that described in 42
CFR 73 for U.S. institutions is in place and will be administered on behalf of all select agent work sponsored by
these funds. Grantees must be willing to address the following key elements appropriate for the foreign institution:
safety, security, training, procedures for ensuring that only approved/appropriate individuals have access to the
select agents, and any applicable laws, regulations and policies equivalent to 42 CFR 73. If this work will not, in
fact, involve select agents (e.g. excluded strains), and you provide documentation satisfactory to the NIH that your
work does not now nor will it in the future (i.e. throughout the life of the award) involve select agents, no
further action will be necessary.
184.108.40.206 Dual User Research of Concern
On March 29, 2012, the Federal government issued a policy for the oversight of life sciences "Dual Use Research of Concern" (DURC). DURC is defined as life sciences research that, based on current understanding, can be reasonably anticipated to provide knowledge, information, products, or technologies that could be directly misapplied to pose a significant threat with broad potential consequences to public health and safety, agricultural crops and other plants, animals, the environment, materiel, or national security. Despite its value and benefits, some research may be misused for harmful purposes. The fundamental aim of this oversight policy is to preserve the benefits of life sciences research while minimizing the risk of misuse of the knowledge, information, products, or technologies provided by such research.
The policy applies to research that involves one or more of 15 agents listed in the policy that can also be reasonably anticipated to produce one or more of 7 effects described in the policy. Research involving these agents and effects will be reviewed by NIH to determine whether it meets the definition of DURC.
For research that may be considered DURC, NIH will work collaboratively with the institution and grantee to develop a risk mitigation plan, which may be implemented through a term of award. For example, NIH may request that institutions periodically review a project for its DURC potential, propose any modifications to the risk mitigation plan, and share any resulting manuscripts with their Program Official prior to submitting the manuscript to a journal.
4.1.25 Reporting and Assurance Requirements for
Institutions Receiving Awards for Training of Graduate Students for Doctoral Degrees
As required by Section 403C of the Public Health Service Act, each institution receiving an NIH award for the
training of graduate students for doctoral degrees must provide information on completion rates and time to degree
to all applicants to doctoral programs supported by NIH training awards. Specifically, institutions must provide
applicants with the following information for the programs to which they apply:
The percentage of students admitted for study who successfully attain a doctoral degree, and
The average time (not including any leaves of absence) between the beginning of graduate study and the receipt
of a doctoral degree.
Institutions affected by this Assurance and information disclosure requirement are doctoral degree
granting institutions that receive any of the following institutional training grant awards or cooperative
agreements from the NIH for the doctoral training of graduate students:
D43, TU2, T15, T32, T37, T90, U2R, U90, and U54/TL1
Institutions are not affected by this requirement if they:
Receive only individual NIH fellowship awards.
Provide training only to undergraduate or master's level students supported through one of the activity codes
Provide only short-term training to doctoral-level health professional students through one of the activity
codes listed above.
Receive an award for one or more of the activity codes for doctoral training of graduate students, but do not
confer doctoral degrees themselves (e.g., teaching hospitals).
Receive an institutional training grant award for doctoral training of graduate students from a Public Health
Service Agency other than the NIH.
In complying with this Assurance and information disclosure requirement, institutions may decide how best to present
the required information to applicants and may wish to consider consolidating data by department or broad program to
which candidates apply, or providing additional information in order to provide context.
Grantees with awards for any of the activity codes listed above are also required to provide corresponding
information on trainees supported by each of their awards when submitting a renewal application or non-competing
continuation progress report (PHS 2590).
4.1.26 Research Involving Recombinant or Synthetic Nucleic Acid Molecules (including Human Gene Transfer Research)
220.127.116.11 Scope and Applicability
The NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines) (March 2013 or latest revision) apply to all research projects (NIH-funded and non-NIH-funded) that involve recombinant or synthetic nucleic acid molecules and are conducted at or sponsored by an organization that receives NIH support for recombinant or synthetic nucleic acid molecule research. A copy of the NIH Guidelines is available at http://oba.od.nih.gov/rdna/nih_guidelines_oba.html.
According to the NIH Guidelines, recombinant and synthetic nucleic acid molecules are defined as (1) molecules that a) are constructed by joining nucleic acid molecules and b) can replicate in a living cell, i.e. recombinant nucleic acids, or (2) nucleic acid molecules that are chemically or by other means synthesized or amplified, including those that are chemically or otherwise modified but can base pair with naturally occurring nucleic acid molecules, i.e. synthetic nucleic acids, or (3)molecules that result from the replication of those described in (1) or (2). The NIH Guidelines apply to both basic and clinical research studies. Specific guidance for the conduct of human gene transfer studies appears in Appendix M of the NIH Guidelines.
Failure to comply with these requirements may result in suspension or termination of an award for recombinant or synthetic nucleic acid molecule research at the organization, or a requirement for NIH prior approval of any or all recombinant or synthetic nucleic acid molecule projects at the organization. Two specific requirements of the NIH Guidelines are discussed below, but the grantee should carefully review the NIH Guidelines in their entirety to ensure compliance with all of the requirements for projects involving recombinant or synthetic nucleic acid molecules.
Recombinant or synthetic nucleic acid research involving select agents also is subject to pertinent CDC and USDA regulations, 42 CFR 73, Select Agents and Toxins; and 7 CFR 331 and 9 CFR 121, Possession, Use, and Transfer of Biological Agents and Toxins.
18.104.22.168 Institutional Biosafety Committee
Each organization that conducts research involving recombinant or synthetic nucleic acid molecules, including contractors under grants, must have policies and procedures to ensure compliance with the NIH Guidelines and must establish a standing IBC. The IBC is required to review each proposed project for recombinant or synthetic nucleic acid molecule experiments to ensure that the procedures, project, personnel, and facilities are adequate and in compliance with the NIH Guidelines. Section IV of the NIH Guidelines specifies the composition of IBCs. A roster of the IBC members and biosketches for each member must be submitted to the NIH's Office of Biotechnology Activities (OBA). At a minimum, the roster should indicate the name of each IBC member, as well as which IBC members are serving as the chairperson, contact person, and, as applicable, experts in biosafety or plant, animal, or human experimentation. Biosketches should include a description of the occupation and professional qualifications of each member. Organizations can register their IBC with OBA on-line by utilizing the IBC Registration Management System (RMS). IBC-RMS can be accessed at: http://ibc-rms.od.nih.gov.
22.214.171.124 Investigators and Institutional Staff
Section IV of the NIH Guidelines also specifies the roles and responsibilities of PIs, biological safety officers (BSOs) and grantee institutions with respect to the safe conduct and oversight of recombinant or synthetic nucleic acid research. Investigators, laboratory staff, BSOs, and institutional officials should read and be aware of their duties and expected biosafety practices, as described by the NIH Guidelines.
126.96.36.199 Safety and Annual Reporting
Appendix M-I-C-4 of the NIH Guidelines requires PIs to report serious adverse events (SAEs) that are both unexpected and possibly associated with the human gene transfer product to OBA and the IBC as soon as possible but no later than 15 calendar days after the sponsor's initial receipt of the information (i.e., at the same time the event must be reported to the FDA). SAEs that are also fatal or life-threatening must be reported no later than seven calendar days. In addition, investigators must submit to OBA annual reports covering certain information about the protocol. Further information about the content of these reports can be found in Appendix M-I-C-3 of the NIH Guidelines. Investigators may use the GeMCRIS database (http://www.gemcris.od.nih.gov/) as an electronic tool to report adverse events or annual reports on human gene transfer trials to NIH OBA.
4.1.27 Research Misconduct
Title 42 CFR 93, PHS Policies on Research Misconduct, Subpart C, "Responsibilities of Institutions"
specifies grantee responsibilities to have written policies and procedures for addressing allegations of research
misconduct, to file an Assurance of Compliance with the HHS Office of Research Integrity, and take all reasonable
and practical steps to foster research integrity. Research misconduct is defined as the fabrication, falsification,
or plagiarism in proposing, performing, or reviewing research, or in reporting research results. The HHS Office of
Research Integrity (ORI) has responsibility for addressing research integrity and misconduct, monitors institutional
investigations of research misconduct and facilitates the responsible conduct of research through education,
preventive, and regulatory activities (http://www.ori.dhhs.gov).
To be eligible for PHS funding an institution must have an assurance on file with ORI stating that it has developed
and will comply with an administrative process for responding to allegations of research misconduct in PHS-supported
research that complies with 42 CFR 93. An institution establishes an assurance when an official signs the
face-page (SF 424 (R&R) or PHS 398) of the grant application form or when the institution files a separate
assurance form. Once established, institutions maintain their assurance by filing the Annual Report on Possible
Research Misconduct (between January 1 and March 1 each year), submitting their policy for responding to allegations
of research misconduct for review when requested by ORI, revising their policy when requested by ORI to bring the
policy into compliance with the PHS regulation, and complying with the PHS regulation.
As stated throughout the NIHGPS, the grantee has primary responsibility for ensuring that it is conducting its
NIH-funded project in accordance with the approved application and budget and the terms and conditions of the award.
The grantee must carry out its responsibilities with extra care where research misconduct has been found or where a
research misconduct investigation has been initiated, as specified in 42 CFR 93, Subpart C. The grantee must report
promptly to ORI any decision to initiate an investigation of research misconduct.
The regulations specify the timing of an institutional investigation, related reporting to ORI, notice to the
respondent, custody of records, documentation, opportunity for respondent to comment on the report, and the
components on a final institutional investigative report.
If a misconduct investigation is initiated, the grantee must take any necessary steps, in addition to its normal and
ongoing responsibilities under the grant, to protect the scientific integrity of the project, protect human subjects
and live vertebrate animals, provide reports to ORI, and ensure the proper expenditure of funds and continuation of
the project during the investigation, if appropriate. ORI staff members are available to help grantees with
investigating and reporting on research misconduct, and IC staff members are available to provide technical
assistance and to work with grantees to protect funded projects from the adverse effects of research misconduct.
The grantee is responsible for the actions of its employees and other research collaborators, including third
parties, involved in the project. When the grantee finds research misconduct by anyone working on an NIH
grant-supported project, whether at the grantee organization or at a third-party organization, the grantee must
assess the effect of that finding on the ability to continue that project, as originally approved by NIH, and must
promptly obtain NIH approval of any intended change of PD/PI or other senior/key personnel. Examples of possible
sanctions by NIH are withdrawal of approval of the PD/PI or other senior/key personnel, debarment, disallowance of
costs associated with the invalid or unreliable research, withholding of a continuation award, or suspension or
termination, in whole or in part, of the current award. These actions are described in Administrative Requirements—Enforcement Actions.
Where research misconduct has affected data validity or reliability, ORI or NIH may require the grantee and its
employee/collaborator authors to submit a correction or retraction of the data to a journal, publish the corrected
data, or both. If the grantee does not comply with this requirement, NIH may invoke its rights, under 45 CFR part 74
or 92, to access the data (including copyrightable material developed under the award), have the data reviewed, and
submit the correction.
4.1.28 Seat Belt Use
Pursuant to EO 13043 (April 16, 1997), Increasing the Use of Seat Belts in the United States, NIH encourages
grantees to adopt and enforce on-the-job seat belt policies and programs for their employees when operating
vehicles, whether organizationally owned or rented or personally owned.
4.1.29 Smoke-Free Workplace
NIH strongly encourages grantees to provide smoke-free workplaces and to promote the nonuse of tobacco products. NIH
defines the term "workplace" to mean office space (including private offices and other workspace),
conference or meeting rooms, corridors, stairways, lobbies, rest rooms, cafeterias, and other public spaces.
4.1.30 Standards of Conduct
NIH requires grantees to establish safeguards to prevent employees, consultants, members of governing bodies, and
others who may be involved in grant-supported activities from using their positions for purposes that are, or give
the appearance of being, motivated by a desire for private financial gain for themselves or others, such as those
with whom they have family, business, or other ties. These safeguards must be reflected in written standards of
conduct. Except as provided below, NIH does not require a grantee to establish separate standards of conduct if it
maintains such standards for its non-grant-supported activities, as long as those standards are consistent with
State and local laws and cover, at a minimum, expected conduct in regard to financial interests, gifts, gratuities
and favors, nepotism, and such other areas as political participation and bribery. The standards also must do the
Address the conditions under which outside activities, relationships, or financial interests are proper or
Provide for advance notification of outside activities, relationships, or financial interests to a responsible
Include a process for notification and review by the responsible official of potential or actual violations of
Specify the nature of penalties that the grantee may impose. These penalties would be in addition to any
penalties that NIH or a cognizant Federal agency may impose for infractions that also violate the terms or
conditions of award.
The grantee is not required to submit its general standards of conduct to NIH for review or approval. However, a copy
must be made available to each of its officers, each employee and consultant working on the grant-supported project
or activity, each member of the governing board, if applicable, and, upon request, to NIH. The grantee is
responsible for enforcing its standards of conduct, taking appropriate action on individual infractions, and, in the
case of financial conflict of interest, informing the IC CGMO if the infraction is related to an NIH award. (A
listing of the NIH GMOs is available at http://grants.nih.gov/grants/stafflist_gmos.htm.)
If a suspension or separation action is taken by a grantee against a PD/PI or other senior/key personnel under an
NIH grant, the grantee must request prior approval of the proposed replacement as specified in Administrative Requirements—Changes in Project and
Budget—Prior Approval Requirements.
The grantee must promptly report issues involving potential criminal violations, such as misappropriation of Federal
funds, to the HHS OIG.
4.1.31 Text Messaging While Driving
Executive Order 13513 (E.O. 13513) requires each Federal agency to encourage contractors, subcontractors, and grant
and cooperative agreement recipients and subrecipients to adopt and enforce policies that ban text messaging while
driving company-owned or -rented vehicles or Government Owned Vehicles, or while driving Personally Owned Vehicles
when on official Government business or when performing any work for or on behalf of the Government.
To further the requirement of encouraging such policies, the NIH encourages grantees to consider new rules and
programs, reevaluate existing programs to prohibit text messaging while driving, and conduct education, awareness,
and other outreach for employees about the risks associated with texting while driving. These initiatives should
encourage voluntary compliance with the grantee agency's text messaging policy while off duty.
For the purposes of this policy and pursuant to E.O. 13513, the following definitions apply:
"Texting" or "Text Messaging" means reading from or entering data into any handheld or other
electronic device, including for the purpose of SMS texting, e-mailing, instant messaging, obtaining
navigational information, or engaging in any other form of electronic data retrieval or electronic data
"Driving" means operating a motor vehicle on an active roadway with the motor running, including while
temporarily stationary because of traffic, a traffic light or stop sign, or otherwise. It does not include
operating a motor vehicle with or without the motor running when one has pulled over to the side of, or off, an
active roadway and has halted in a location where one can safely remain stationary.
4.1.32 Trafficking in Persons
This government-wide award term implements Section 106 (g) of the Trafficking Victims Protection Act (TVPA) of 2000,
as amended (22 U.S.C. 7104), located at 2 CFR 175. This is implemented in accordance with OMB Interim Final
Guidance, Federal Register Volume 72, No. 218, November 13, 2007. A Final Notice is expected to be issued in the
future; however, HHS agencies have implemented this award term based on the Interim Final Guidance.
In accordance with the statutory requirement, in each agency award under which funding is provided to a private
entity, section 106(g) of the TVPA, as amended, requires the agency to include a condition that authorizes the
agency to terminate the award, without penalty, if the recipient or a subrecipient —
Engages in severe forms of trafficking in persons during the period of time that the award is in effect;
Procures a commercial sex act during the period of time that the award is in effect; or
Uses forced labor in the performance of the award or subawards under the award.
Full text of the award term is provided at 2 CFR 175.15.
4.1.33 USA Patriot Act
The Uniting and Strengthening America by Providing Appropriate Tools Required to Intercept and Obstruct Terrorism Act
(USA PATRIOT Act) (P.L. 107-56) amends 18 U.S.C. 10 and provides criminal penalties for possession of any biological
agent, toxin, or delivery system of a type or in a quantity that is not reasonably justified by a prophylactic,
protective, bona fide research, or other peaceful purpose. The Act also establishes restrictions on access to
specified materials. "Restricted persons," as defined by the Act, may not possess, ship, transport, or
receive any biological agent or toxin that is listed as a select agent (see Public
Health Security and Bioterrorism Preparedness and Response Act in this section).
4.2 Appropriation Mandates
The following statutory provisions limit the use of funds on NIH grants, cooperative agreements, and contract awards.
These are provided separately in this section since they are subject to change annually based on specific
appropriation language that restricts the use of grant funds. References to "Act" in these sections refer
to the governing HHS annual appropriation Act. A list of Appropriation Mandates applicable to each fiscal year can
be found on the OER Web site.
4.2.1 Acknowledgment of Federal Funding
All HHS grantees must acknowledge Federal funding when issuing statements, press releases, requests for proposals,
bid invitations, and other documents describing projects or programs funded in whole or in part with Federal money.
Grantees are required to state (1) the percentage and dollar amounts of the total program or project costs financed
with Federal money and (2) the percentage and dollar amount of the total costs financed by nongovernmental
4.2.2 Certification of Filing and Payment of Taxes
None of the funds appropriated or otherwise made available by the governing appropriation Act may be used to enter
into a contract in an amount greater than $5,000,000 or to award a grant in excess of such amount unless the
prospective contractor or grantee certifies in writing to NIH that, to the best of its knowledge and belief, the
contractor or grantee has filed all Federal tax returns required during the 3 years preceding the certification, has
not been convicted of a criminal offense under the Internal Revenue Code of 1986, and has not more than 90 days
prior to certification, been notified of any unpaid Federal tax assessment for which the liability remains
unsatisfied, unless the assessment is the subject of an installment agreement or offer in compromise that has been
approved by the Internal Revenue Service and is not in default, or the assessment is the subject of a non-frivolous
administrative or judicial proceeding.
4.2.3 Dissemination of False or Deliberately Misleading Information
None of the funds made available in the governing appropriations Act may be used to disseminate information that is deliberately false or misleading.
4.2.4 Gun Control
The FY 2012 Appropriations Act provides that NIH funds may not be used, in whole or in part, to advocate or promote gun control.
4.2.5 Human Embryo Research and Cloning Ban
NIH funds may not be used to support human embryo research. NIH funds may not be used for (1) the creation of a human
embryo or embryos for research purposes; or (2) for research in which a human embryo or embryos are destroyed,
discarded, or knowingly subjected to risk of injury or death greater than that allowed for research on fetuses in
utero under 45 CFR 46.204(b) and subsection 498(b) of the PHS Act (42 U.S.C. 289g(b)). The term "human embryo
or embryos" includes any organism not protected as a human subject under 45 CFR 46, as of the date of enactment
of the governing appropriations act, that is derived by fertilization, parthenogenesis, cloning, or any other means
from one or more human gametes or human diploid cells.
In addition to the statutory restrictions on human fetal research under subsection 498((b) of the PHS Act, by
Presidential memorandum of March 4, 1997, NIH is prohibited from using Federal funds for cloning of human
4.2.6 Lobbying—Appropriation Prohibition
NIH appropriated funds may not be used, other than for normal and recognized executive-legislative relationships for publicity or propaganda purposes, for the preparation, distribution, or use of a kit, pamphlet, booklet, publication, electronic communication, radio, television, or video presentation designed to support or defeat the enactment of legislation before the Congress or any State or local legislature or legislative body, except in presentation to the Congress or any State legislature or local legislature itself or designed to support or defeat any proposed or pending regulation administrative action, or order issued by the executive branch of any State or local government, except in presentation to the executive branch of any State or local government itself. No part of any governing appropriation act shall be used to pay the salary or expenses of any grant or contract recipient, or agent acting for such recipient, related to any activity designed to influence the enactment of legislation, appropriations, regulation, administrative action, or Executive Order proposed or pending before the Congress or any State government, State legislature or local legislature or legislative body other than for normal and recognized executive-legislative relationships or participation by an agency or officer of a State, local or tribal government in policymaking and administrative processes within the executive branch of that government. No part of any governing appropriation Act shall be used for any activity to advocate or promote any proposed, pending or future Federal, State or local tax increase, or any proposed, pending, or future requirement or restriction on any legal consumer product, including its sale or marketing, including but not limited to the advocacy or promotion of gun control, except as described above. Also see Public Policy Requirements and Objectives - Lobbying Prohibition, Appropriation Mandates - Gun Control and Cost Considerations - Allowability of Costs and Activities.
4.2.7 Promotion or Legalization of Controlled Substances
Grantees are prohibited from knowingly using appropriated funds to support activities that promote the legalization
of any drug or other substance included in Schedule I of the schedules of controlled substances established by
section 202 of the Controlled Substances Act, 21 U.S.C. 812 except for normal and recognized executive-congressional
communications. This limitation does not apply if the grantee notifies the GMO that there is significant medical
evidence of a therapeutic advantage to the use of such drug or other substance or that federally sponsored clinical
trials are being conducted to determine therapeutic advantage (see also Public Policy Requirements/Controlled
4.2.8 Restriction on Abortion Funding
NIH appropriated funds and funds in any trust fund to which funds are appropriated in the governing appropriation Act
may not be spent for any abortion. None of the funds appropriated in the governing appropriation Act, and none of
the funds in any trust fund to which funds are appropriated in this Act, shall be expended for health benefits
coverage that includes coverage of abortion. The term "health benefits coverage" means the package of
services covered by a managed care provider or organization pursuant to a contract or other arrangement.
188.8.131.52 Exceptions to Restrictions on Abortions
The limitations established in the preceding section shall not apply to an abortion — (1) if the
pregnancy is the result of an act of rape or incest; or (2) in the case where a woman suffers from a physical
disorder, physical injury, or physical illness, including a life endangering physical condition caused by or
arising from the pregnancy itself, that would, as certified by a physician, place the woman in danger of death
unless an abortion is performed.
Nothing in the preceding section shall be construed as prohibiting the expenditure by a State, locality,
entity, or private person of State, local, or private funds (other than a State's or locality's contribution of
Medicaid matching funds).
Nothing in the preceding section shall be construed as restricting the ability of any managed care provider
from offering abortion coverage or the ability of a State or locality to contract separately with such a
provider for such coverage with State funds (other than a State's or locality's contribution of Medicaid
(1) None of the funds appropriated to NIH may be made available to a Federal agency or program, or to a State or
local government, if such agency, program, or government subjects any institutional or individual health care
entity to discrimination on the basis that the health care entity does not provide, pay for, provide coverage
of, or refer for abortions. (2) In this subsection, the term "health care entity" includes an
individual physician or other health care professional, a hospital, a provider-sponsored organization, a health
maintenance organization, a health insurance plan, or any other kind of health care facility, organization, or
4.2.9 Restriction on Distribution of Sterile Needles
NIH appropriated funds may not be used to carry out any program of distributing sterile needles or syringes for the hypodermic injection of any illegal drugs.
4.2.10 Salary Cap/Salary Limitation
None of the funds appropriated in the governing appropriation Act for the NIH (the Act), shall be used to pay the salary of an
individual through a grant or other extramural mechanism at a rate in excess of that prescribed in the Act. Applications and
proposals with categorical direct cost budgets reflecting direct salaries of individuals in excess of the rate prescribed in the Act will be adjusted in accordance with the legislative salary limitation. Current and historical
information on the applicable salary cap for each fiscal year is on the OER Salary Cap Summary webpage.