Q&A: Institutional Responsibilities Under a Federalwide Assurance

In a recent webinar, Advarra regulatory experts presented on the topic titled Institutional Responsibilities Under a Federalwide Assurance (FWA). Our experts discussed what an FWA is, its requirements and how the assurance process has changed in response to revisions to 45 CFR 46, the Common Rule. Due to time constraints, we were unable to answer all of the questions posed during the Q&A period, so our experts have responded to additional questions in this blog.

Q: If a U.S. institution elects to “check the box” under item 4b of its FWA application, does the institution agree to apply 45 CFR Part 46, Subpart A: Basic HHS Policy for Protection of Human Subjects (the Common Rule) along with 45 CFR Part 46: Subparts B – E to its non-exempt human subjects research regardless of source of support?
A: It depends. Within the “applicability” section of the FWA , U.S. institutions may voluntarily elect to apply either the Common Rule (45 CFR 46 subpart A) or the entirety of 45 CFR part 46 (i.e., 45 CFR 46, subparts A-E) to all of its non-exempt human subjects research regardless of source of support. Thus, if an institution selects the first option under 4b of its FWA application then the institution only commits to applying the Common Rule to its non-exempt human subjects research regardless of support. Conversely, if an institution selects the second option under 4b of its FWA application, then the institution commits to applying the Common Rule and subparts B-E of 45 CFR 46 to its non-exempt human subjects research regardless of support.

For additional information, please view the OHRP website’s section on registering IRBs and obtaining FWAs.

Q: If we “check the box,” do we have to disclose this to research participants in the informed consent process?
A: Such a disclosure is not required by the regulations (although an IRB could choose to require that this information be disclosed).

Q: Is it still necessary to submit and maintain an IRB roster with OHRP?
A: OHRP has not yet issued clarification on this point.

Q: If a laboratory has an IRB and conducts internal and external research for presentations and publication, should the laboratory apply for an FWA?
A: Before answering the question, it is important to explain the differences between the IRB registration process and the FWA process. The IRB registration process is applicable to any IRB that reviews research conducted or supported by the Department of Health and Human Services (HHS) or reviews research subject to Food and Drug Administration (FDA). The FWA process applies to institutions engaged in non-exempt human subjects research supported by a Common Rule department or agency. See OHRP’s Engagement Guidance Document.

Given this, if the laboratory is not engaged (as described in OHRP guidance) in research conducted or supported by a Common Rule department or agency, an FWA is not needed. If the IRB affiliated with the laboratory reviews HHS supported or conducted research, or research subject to FDA oversight, then the IRB must be registered with HHS.

Q: How can the exemption determination come before the “research” and “human subject research” determinations?
A: Before considering whether an activity meets one or more of the exemption categories, one must first determine whether an activity involves “human subjects” and “research” (as defined in the Common Rule). For the purposes of the presentation, we discussed exemptions first. OHRP’s mini tutorial on engagement has an excellent description of the questions one should ask before beginning an engagement analysis.

Q: What does the term “supported” mean in the context of “research conducted or supported by a federal department/agency”?
A: While “supported” is not defined in 45 CFR Part 46, it generally refers to the mechanisms through which a federal department or agency enables an institution to conduct a research activity (generally through the provision of funds). “Support” as used in the Common Rule includes (but is not limited to) the following mechanisms: grants, awards, contracts, and cooperative agreements. It also includes other situations where the federal government provides other types of support including, but not limited to the provision of supplies, products, drugs, employee’s time, and identifiable private information collected for research purposes.

The NIH’s Grants and Fundings website provides additional examples of HHS support mechanisms.

Q: Is “external IRB” defined anywhere? If a large health system has a corporate IRB, would it be appropriate to have all divisions in the health system have an FWA and rely upon the corporate IRB or “external” IRB?
A: For the purposes of the Common Rule, consider an “external IRB” to be an “IRB that is not operated by the institution [engaged in/conducting the research]” (see 45 CFR 46.103(e)). This could be an independent IRB (e.g., a commercial IRB), or an IRB operated by another institution (e.g., University X relying on the IRB operated by Hospital Y).

Q: OHRP audits: Can you explain more when are these conducted, how often, etc.? What are the elements of the review?
A: Please refer to the OHRP Guidance Document titled Compliance Oversight Procedures for Evaluating Institutions (2009), available on the OHRP website. This document discusses the types of evaluations OHRP conducts and the scope of such evaluations.

Q: What is the most current available assurance OHRP training?
A: Please refer to the OHRP website regarding assurance training. However note what OHRP states at the beginning of this assurance training webpage, i.e.,this assurance training reflects the pre-2018 Common Rule. It does not reflect the requirements in the 2018 Common Rule, for which the general compliance date was January 21, 2019.

Q: Say an independent research site has no internal IRB and is using the sponsor’s selected central IRB for each study the site participates in. Must the site declare one central IRB on the FWA, and then all of their studies must go through the chosen central IRB on the FWA regardless of what sponsors choose?
A: In its “FWA Instructions” OHRP provides the following: “This Institution assures that it will rely upon only Institutional Review Boards (IRBs) registered with OHRP to review the research to which this FWA applies. Designate all of your institution’s internal IRBs that review research under this FWA. If your institution has no internal IRBs, designate the external IRB that reviews all of the research to which this FWA applies or, if multiple external IRBs are relied upon, list the external IRB that reviews the largest percentage of research to which this FWA applies.

Note: Institutions designating internal IRBs do not need to designate any of the external IRBs upon which it relies.”

To that end, if the institution has an internal IRB designated on the FWA, it does not need to designate any of the external IRBs upon which it relies. And remember, if the independent research site is not engaged in research supported by a Common Rule department or agency (e.g., research only subject to the FDA regulations), then the independent research site need not obtain an FWA.

Q: If an institution participating in a multisite study has checked the box, but all the other participating sites have not, how does that affect the institutions that have not checked the box?
A: In this situation, the conduct of the study at the site(s) that have checked the box must be conducted in compliance with the Common Rule. While there is no official guidance available on how institutions might handle this situation, it is legally permissible for the institutions (and IRBs) to determine only the sites with the box checked on the FWA would be subject to the Common Rule (in addition to the other regulatory frameworks that might apply to the study).

Q: Is an IRB authorization agreement needed for multisite, industry-sponsored research under central IRB?
A: It depends. If one of the sites is operated by a Common Rule department/agency (e.g., one of the sites is a VA Medical Center), then at a minimum the site and central IRB need to have IRB reliance documentation in place (to the extent required by the Terms of the Assurance and 45 CFR 46.103(e) in the revised Common Rule); additionally, if one of the sites “checks the box” on the FWA, then that site would also need to have IRB reliance documentation in place (with the same caveats as previously discussed).

Q: Does an institution with no IRB need only have a procedure for reporting, and simply rely on the external IRB for everything else?
A: If an FWA-holding institution relies entirely on external IRBs, it still must ensure the terms of its FWA with HHS are satisfied. Specifically, the institution would still need to ensure the written procedure requirements outlined in the FWA Terms are satisfied. One way to ensure the written procedure requirements outlined in the FWA Terms are satisfied is to enter into a comprehensive IRB Authorization Agreement which could collectively describe which written procedures will be followed for the studies covered by the IRB Authorization Agreement

Q: Do commercial IRBs fall under OHRP with the revised Common Rule?
A: All IRBs reviewing research subject to the Common Rule must comply with the Common Rule (see 45 CFR 46.101(a) in the revised Common Rule). To that end, if a commercial IRB reviews HHS conducted or supported research, it would fall under OHRP’s compliance oversight authority for those studies. Additionally, a commercial IRB would fall under OHRP’s compliance oversight authority for any “check the box” studies it might review.

To learn more about Federalwide Assurances and its role in clinical research, watch the webinar Institutional Responsibilities Under a Federalwide Assurance.

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