Assurance Process - FAQs:

An assurance of compliance is a written document submitted by an institution (not an Institutional Review Board) that is engaged in non-exempt human subjects research conducted or supported by HHS. Through the assurance of compliance, an institution commits to HHS that it will comply with the requirements set forth in the regulations for the protection of human subjects at 45 CFR part 46. The Federalwide Assurance is the only type of assurance of compliance accepted and approved by OHRP.

In general, an institution is considered to be engaged in human subjects research when its employees or agents:

(1) obtain data about living individuals for research purposes through intervention or interaction with them,

(2) obtain individually identifiable private information for research purposes (45 CFR 46.102(d),(f)) http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html#46.102; or

(3) obtain the informed consent of human subjects.

Employees and agents, including students, are individuals performing institutionally designated activities and acting on behalf of the institution or exercising institutional authority or responsibility.

In general, an institution is considered to be engaged in human subjects research whenever it receives a direct HHS award to support such research, even if all of the human subjects activities will be performed by agents or employees of another institution. In general, simply informing potential subjects about a research study is not considered engagement in research. Also, providing written information about a research study, including how to contact the investigators for information and enrollment, and seeking and obtaining prospective subjects' permission for investigators to contact them are not considered engagement in research. However, obtaining informed consent from a research participant is considered engagement in research.

[For details, please see OHRP guidance on this topic at: http://www.hhs.gov/ohrp/policy/engage08.html, specifically, Section (B)(4).]

The FWA covers all non-exempt human subjects research at the submitting institution that is HHS-conducted or -supported or funded by any other federal department or agency that has adopted the Common Rule and relies upon the FWA. It is not project specific. Domestic institutions may voluntarily extend their FWA to cover all human subjects research at the submitting institution regardless of the source of support for the particular research activity.

The key features of the Federalwide Assurance (FWA) are the following:

a)   The identifying information for the institution filing the FWA, the Human Protections Administrator (or a reliable point of contact) at the institution, and the institutional official signing the FWA;

b)   A list of the institution’s legal components that operate under different names that will be covered by the FWA and the city and state or country where the component is located. (legal components are generally defined as parts of your institution that may be viewed as separate organizations, but remain part of the legal entity or institution, for example, ABC University can list its XYZ University Hospital, KLM School of Public Health, and EFG Institute for International Studies as components);

c)   A statement of ethical principles to be followed in protecting human subjects of research;

d)   An applicability statement indicating that the FWA applies whenever the institution becomes engaged in human subjects research conducted or supported by any United States (U.S.) federal department or agency that has adopted the U.S. Federal Policy for Protectionof Human Subjects (known as the Common Rule), unless the research is exempt from Common Rule requirements or a Common Rule agency or department determines the research will be conducted under a separate assurance of compliance. U.S. institutions may voluntarily extend the Common Rule or 45 CFR part 46 to all research conducted by the institution regardless of the source of support;

e)   An assurance of compliance indicating that the institution will comply with the Terms of the FWA.  An institution outside of the U.S. also must assure that it will comply with one or more procedural standards whenever it engages in research covered by the FWA. A list of 6 such standards is included or an institution can submit another standard for the protection of human subjects that is recognized by the Common Rule departments and agencies. (See Terms of Assurance, section 3(b));

f)    The designation of all internal IRBs that will review the research covered by the FWA. If the institution has no internal IRB, it must designate the external IRB that reviews all research covered by the FWA.  If the institution relies upon multiple external IRBs, the institution should designate the external IRB that reviews the largest percentage of the research covered by the FWA.  All IRBs designated on an institution’s FWA must be registered [http://www.hhs.gov/ohrp/assurances/irb/index.html] with OHRP before the FWA can be approved).  Please note that all IRBs reviewing research covered by an instituion’s FWA must be registered whether or not they are designated on the institution’s FWA;

g)   Whenever the Institution relies upon an IRB operated by another institution or organization for review of research covered by the FWA, the institution must ensure that this arrangement is documented by a written agreement between the institution and the other organization or institution operating the IRB. The agreement must outline their relationship and include a commitment that the IRB will adhere to the requirements of the Institution’s FWA.  OHRP’s sample IRB Authorization Agreement may be used for this purpose, or the parties involved may develop their own agreement.  This agreement must be kept on file at both institutions/organizations and made available to OHRP or any U.S. federal department or agency conducting or supporting research covered by the FWA upon request; 

The signature of an official authorized to represent the institution, identified on the FWA as Signatory Official. The Signatory Official must assure that human subjects research to which the FWA applies is conducted in accordance with the Terms of Assurance.  The Signatory Official must electronically sign the FWA using the electronic submission system available through the OHRP website at: http://ohrp.cit.nih.gov/efile/, unless the institution lacks the ability to submit its FWA electronically.The Signatory Offical typically is someone at the level of President, Chief Executive Officer, Chief Operating Officer, Director General, or Chancellor.

OHRP is sometimes asked whether, if an international institution selects a procedural standard under the FWA that has less stringent requirements than 45 CFR part 46, the institution may disregard the more stringent requirements of 45 CFR part 46.

It is current OHRP policy that in the absence of an OHRP determination that a procedural standard affords protections equivalent to the protections provided by 45 CFR part 46, the requirements of 45 CFR part 46 must be applied to all research conducted or supported by HHS.

As described in a July 7, 2006 Federal Register notice (71 FR 38645) it is OHRP’s position that if an international institution selects a procedural standard under its FWA other than 45 CFR part 46, any requirements of 45 CFR part 46 still must be satisfied for non-exempt human subject research that is conducted or supported by HHS.

For example, the International Conference on Harmonization E-6 Guidelines for Good Clinical Practice (ICH-GCP-E6) do not specifically limit use of expedited review for research undergoing continuing review by the IRB. For research conducted or supported by HHS, if an international institution selected ICH-GCP-E6 as its primary procedural standard  on its FWA, the IRB may only use an expedited review procedure to conduct continuing review of HHS-conducted or supported research if the research qualifies for expedited review as provided for under HHS regulations at 45 CFR 46.110.

Please note that the statements above pertain to compliance with the requirements of 45 CFR part 46 for non-exempt human subjects research that is conducted or supported by HHS. If the institution needs guidance regarding implementation of the Common Rule and/or other applicable U.S. federal regulations for research that is not conducted or supported by HHS, the institution should contact appropriate officials at the U.S. federal department or agency conducting or supporting the research.

Employees and agents of the institution holding an approved FWA are covered whenever they are involved in the conduct of research covered by the FWA. Employees and agents, including students, are individuals performing institutionally designated activities and acting on behalf of the institution or exercising institutional authority or responsibility.

An institution holding an OHRP-approved FWA (hereafter referred to as the assured institution) may extend the applicability of its FWA to cover two types of collaborating individual investigators: collaborating independent investigators and collaborating institutional investigators.

1. A collaborating independent investigator is:
   1. not otherwise an employee or agent of the assured institution;
   2. conducting collaborative research activities outside the facilities of the assured institution; and
   3. not acting as an employee of any institution with respect to his or her involvement in the research being conducted by the assured institution.
2. A collaborating institutional investigator is:
   1. not otherwise an employee or agent of the assured institution;
   2. conducting collaborative research activities outside the facilities of the assured institution;
   3. acting as an employee or agent of an institution that does not hold an OHRP-approved FWA with respect to his or her involvement in the research being conducted by the assured institution; and employed by, or acting as an agent of, an institution that does not hold an OHRP-approved FWA and does not routinely conduct human subjects research.

The extension of an assured institution’s FWA to cover a collaborating individual investigator should be documented using an Individual Investigator Agreement (IIA) or another similar agreement developed by the institution holding the FWA (see http://www.hhs.gov/ohrp/policy/guidanceonalternativetofwa.html for OHRP’s guidance on the use of the IIA and the link to the sample IIA document).

If HHS-conducted or -supported human subjects research activities routinely occur at a non-assured institution, the institution should obtain an OHRP-approved FWA, and the IIA (or similar agreements) should not be used. Also, if the non-assured institution is the primary awardee for an HHS-supported award providing support for non-exempt human subjects research, the institution must obtain its own OHRP-approved FWA. If an institution is uncertain about the need for its own FWA, it should consult with OHRP.

NOTE: All previous types of sample agreements to cover an independent investigator [i.e., Agreement for Independent Investigators (AII), Non-Institutional Investigator Agreement (NIA), and Unaffiliated Investigator Agreement (UIA)] have been replaced by the sample Individual Investigator Agreement (IIA). Previously executed AIIs, NIAs, and UIAs may remain in effect until all applicable research that has already been initiated is completed or until the previous agreement has been replaced by a new Individual Investigator Agreement modeled on the OHRP sample IIA, or by a comparable written agreement developed by an assured institution.

The FWA Signatory Official should be a high-level institutional official who has the authority to represent the institution named in the Federalwide Assurance (FWA), as well as all the institutional components listed in the FWA. Entities that the Signatory Official is not authorized to represent may not be covered under the FWA. This person is usually the President, Chief Executive Officer, Chief Operating Officer, Director General, or Chancellor.

The intent in requiring that the Signatory Official be a high-level individual is two-fold. First, OHRP encourages institutions to promote a culture of conscience for the ethical conduct of human subjects research at the highest level within the institution. Second, the Signatory Official should be at a level of responsibility that would allow authorization of necessary administrative or legal action should that be required. OHRP recommends that the Signatory Official not be the chair or member of any IRB designated under the FWA.

If you have questions about submitting an FWA, you should contact the Assurance Coordinator assigned to your state or international region (see the OHRP website at http://www.hhs.gov/ohrp/assurances/status/contact/index.html).

With electronic submission of your institution’s Federalwide Assurance (FWA), which is required unless your institution lacks the ability to submit its FWA electronically, the Signatory Official, Human Protections Administrator, and the individual who submitted the FWA will receive an automatically generated email when OHRP approves the FWA.  A copy of the approved FWA will be attached to that email.

If human subjects research conducted or supported by a non-HHS Common Rule department or agency involves collaborating institutions that do not hold an FWA or other applicable OHRP-approved assurance of compliance for federalwide use, OHRP does not require the collaborating institutions to obtain FWAs, but an FWA may be required by the non-HHS department or agency conducting or supporting the human subjects research.

For such situations, while obtaining an FWA would be one option for the collaborating institutions to comply with the assurance of compliance requirement of the Common Rule §__.103(a) [http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html#46.103], obtaining an FWA would not be required by HHS. When requests for guidance on this topic are received by OHRP, OHRP will refer the requestor to appropriate officials at the conducting or supporting Common Rule department or agency for assistance in deciding on an appropriate assurance mechanism.

When the allegations or indications of noncompliance (complaints) are limited solely to the research activities conducted or supported by another Common Rule department or agency, for Human Research Protections (OHRP) will refer the matter to appropriate officials at the other department or agency for further investigation and action, as appropriate. OHRP’s Division of Compliance Oversight (DCO) will not be involved in the conduct of the investigation unless the relevant department or agency requests OHRP’s involvement. When the other department or agency completes its investigation without OHRP involvement, a report on the outcome of the investigation should be provided to OHRP.

Yes, whenever non-U.S. institutions are engaged in non-exempt HHS-supported or -conducted human subjects research, the HHS human subjects protection regulations, 45 CFR part 46, apply.

Please see: http://www.hhs.gov/ohrp/assurances/assurances/filasurt.html