Single IRBs and IRB Authorization Agreements

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CATS IRB was upgraded successfully on June 26, 2023. External IRB users have a siginficant (positive!) process change. Learn more: 


Effective January 25, 2018, the NIH has mandated that all domestic sites participating in a non-exempt, multi-site research study (where study activities outlined in a single protocol are carried out at multiple institutions) use a single IRB (sIRB).

Effective January 20, 2020, OHRP requires a sIRB for all domestic sites participating in a non-exempt, cooperative research study (two or more institutions coordinate to complete a portion of the research outlined in a specific protocol).

Authorization Agreements

An authorization agreement refers to the formal written agreement that documents respective authorities, roles, responsibilities, and communication between an institution/organization serving as the IRB of Record (Reviewing IRB) and the institution relying on that IRB (Relying IRB). This term includes: reliance agreement, cooperative agreement, master services agreement (MSA), master joint agreement (MJA), or umbrella agreement.

Researchers seeking to rely on the IRB of another institution or have Penn State's IRB serve as the reviewing IRB for another institution must have an IRB authorization agreement. These agreements are executed between a Reviewing IRB and one or more Relying Institutions and delineate the roles and responsibilities of the involved parties. The agreements can be for a single research study or for multiple studies (e.g., a master reliance agreement). The authorization agreement is negotiated and finalized by the Penn State IRB and reviewed by Penn State’s legal counsel, as needed. 

Authorizations agreements do not replace the need for IRB approval, and all human subjects research protocols still require a submission in CATS IRB, regardless of who may serve as the reviewing IRB. Even with an authorization agreement, researchers must still obtain IRB approval from the reviewing IRB and an acknowledgement of that approval from the HRPP before beginning any study activities and before funds can be released. The Penn State principal investigator remains responsible for ensuring all of Penn State’s institutional requirements are met before beginning the research and throughout the course of the research activities.

Note:  Penn State is a member of the SMART IRB Master Common Reciprocal Institutional Review Board Authorization Agreement and has Master Service Agreements in place with multiple commercial IRBs (e.g., WCG, Advarra). If an agreement outside of these already executed reliance agreements is required, it is not uncommon for new authorization agreements to take months because of the various institutional offices that must be involved. Researchers are advised to keep this in mind when considering a reliance request.

sIRB Review Process

sIRB review is more than just an IRB review. It includes other components, such as those depicted in the image below.

Picture of different regulatory stakeholders included in the Single IRB review process

sIRB vs Local Review

The image below depicts the different responsibilities of the sIRB compared to the local institution. 

A picture of Single IRB review versus local IRB review

Multi-Site Research

Multi-site studies use the same research procedures (i.e., protocol) outlined in a single protocol that is carried out at multiple institutions.

Examples of Multi-site Research

  • Protocols implemented at multiple locations that address the same research questions, involve the same methodologies, and evaluate the same outcomes, such as clinical trials
  • Sites that are accruing research participants for studies that are identical except for variations due to local context consideration

Cooperative Research

Cooperative or collaborative research is where two or more institutions coordinate to complete a portion of the research outlined in a protocol at their respective locations.

Examples of Cooperative Research

  • A study where one institution gathers the data and another institution analyzes the data
  • Protocols that are split between institutions, where one institution may collect a portion of the data, and another institution collects a different portion of the data

Note that the Single IRB requirement only applies to institutions engaged in non-exempt human subject research. For guidance determining if your involvement qualifies as "institutional engagement" in human subjects research, refer to the video provided by the Office for Human Research Protections.

Policies regarding willingness to serve as a Reviewing IRB are specific to each institution. To request that an institution’s IRB serve in this capacity, work with the IRB at that institution (and the principal investigator at that institution, if applicable) to confirm their policy before proceeding. The Penn State IRB makes the final determination regarding whether to be a Reviewing IRB or a Relying IRB when Penn State is engaged in the human subject research study in question.

For questions about Penn State HRPP reliance processes, please contact:

You can also schedule a meeting via Bookings.


Request to Rely (R2R) on an External IRB

5-step R2R at the Penn State HRPP

Investigators should be aware that reliance arrangements frequently require additional work on the part of the local study team, including submission to the Penn State HRPP and the external IRB, as well as managing communication between these offices. For minimal risk research, review times for external IRB protocols can exceed review times for minimal risk projects approved by a local IRB. See the ‘SMART IRB Relying on an External IRB: FAQs for Research Teams’ and the ‘SMART IRB Relying Investigator Checklist’ for additional details about local study team responsibilities.

The section entitled, ‘Reliance on an External IRB for Review of Human Subject Research Studies’ in the Investigator Manual (HRP-103) provides the criteria that Penn State’s IRB considers when deciding to cede review to an external IRB. Typically, we require that the Reviewing IRB is part of an AAHRPP accredited institution or organization. See the AAHRPP website for a list of accredited institutions/organizations. 

NOTE: The Penn State HRPP will only enter into reliance arrangements when our site is engaged in non-exempt human subject research. See "Worksheet – Exemption Determination (HRP-312)" within the CATS library to assess whether the activities carried out by our site meets any of the listed criteria. If so, local IRB review should be sought instead.

Investigators requesting a reliance determination should complete a Reliance Request Form. This form must be completed PRIOR to a submission in CATS IRB.

Penn State’s HRPP CANNOT guarantee their willingness to support the use of the sIRB without the submission of this form. If an institution is listed under the "External IRB" list in CATS IRB, there is still a need to complete the Reliance Request Form and confirm the details related to the authorization agreement that will be used. Determinations are made on a case-by-case basis. Penn State will not enter into authorization agreements for research determined to be exempt.

If you are not ready to submit a protocol, but are submitting a grant proposal that includes a single IRB plan, the HRPP has issued a statement confirming our understanding of the NIH single IRB policy and agreeing to rely on sIRBs that meet certain criteria (e.g., using SMART IRB Agreement). The full statement is available for download and may be included in grant applications.

If the Reviewing IRB is requiring a specific letter of support be signed for a grant proposal, or the criteria outlined in the attached statement are not met, please submit the request via the Reliance Request Form at least two weeks before the grant submission deadline.

A CATS submission should only occur after the Penn State HRPP has agreed to the reliance arrangement proposed within STEP TWO.

All human subject research being reviewed by an external IRB, through either a master reliance agreement with a commercial IRB, the SMART IRB Reliance Agreement, or through study-specific reliance agreements with other institutions, must submit an external IRB submission to the HRPP office through CATS for registration and review of local requirements (e.g. conflict of interest, education requirements, state law, institutional policy, ancillary office review). The external IRB submission will be reviewed and returned to you with instruction to submit to the reviewing IRB. Any documents required by the Reviewing IRB should be included with your submission (e.g. local context forms, reliance documents requiring IRB/institutional signatures).

Visit the CATS IRB Help Center to review the "External IRB Submissions" job aid for more information about submitting an external IRB submission to the Penn State HRPP.

For federally funded research, the external IRB submission should only be submitted to the Penn State HRPP after the funding agency has agreed to the proposed sIRB plan.

Reliance on an external IRB is specific to the ethical review of the study, as specified under the HHS regulations at 45 CFR Part 46 and/or FDA regulations at 21 CFR Part 56. Questions about how to submit to the external (Reviewing) IRB should be directed to that IRB. The reliance arrangement may involve standard operating procedures (SOPs) that describe with whom and how to communicate with the external IRB. In addition, the external IRB may have its own distinct steps/processes in its submission process.

Reliance requests that do not fall under an existing Master Agreement with Penn State

Penn State institutional language will likely be required in the consent forms approved by the external IRB. This language can be found in HRP-109 - Consent Language Document. This language should match the Penn State template consent language from the following sections as applicable:

  • Compensation for Injury
  • Compensation for Participation
  • Radiation Safety Language (provided after the local Radiation Safety review)
  • Authorization to Use and Disclose Information for Research Purposes


See the 'SMART IRB Informed Consent Documents: Inserting Local Context Language' for additional details about the process for review and approval of local consent forms.

Reliance requests that fall under an existing Master Agreement with Penn State

The IRBs listed below have existing master agreements with Penn State and therefore have Penn State standard consent language and local context information on file. Please reach out to the point of contacts listed below for questions related to submitting to one of these IRBs. For questions about Penn State requirements or CATS IRB submissions please reach out the appropriate HRPP staff.

When using WCG:
When using Advarra:
  • What is the process to use Advarra?
    • Once you are ready to submit to Advarra, please visit
    • Select either the investigator application or protocol application, depending on what you wish to submit to Advarra
    • CIRBI helpdesk can be reached at Email: or toll free at 1-866-99CIRBI (1-866-992-4724)
  • For any questions on how to submit, please contact


When using NCI CIRB:


Final versions of the study documents approved by the external IRB, alongside the external IRB approval letter, should be attached prior to resubmission of the external IRB submission in CATS. Final acknowledgement of the submission cannot occur until all applicable ancillary reviews have been completed. Because ancillary reviews are by definition ancillary to the IRB review, all criteria for setting ancillary reviews is the same regardless of whether an external IRB is being used.

Please note that research activities cannot begin at any Penn State location until acknowledgment of this final submission has been provided, even if the external IRB has provided their review/approval of the protocol.

Post-Approval R2R Requirements

After an Acknowledgement of Reliance on an External IRB is issued, the following changes must be submitted to the IRB Office for review:

  • Revised consent forms
    •  While all revised consent forms must be submitted in CATS, researchers may implement these changes at PSU once they are approved by the Reviewing IRB UNLESS the proposed changes impact local considerations (e.g., ancillary reviews, PSU standard consent language). Changes that impact local considerations must await PSU HRPP acknowledgement prior to their implementation
  • Changes in study team members (for a training status check)
  • Changes in funding sources
  • Changes in the financial interest of study team member(s) including the PI
  • Changes that impact institutional requirements (e.g., ancillary reviews, EIM form, HRP-880, HRP-598)


Visit the CATS IRB Help Center to review the "External IRB Submissions" job aid for more information about submitting a modification to the Penn State HRPP for an external IRB submission.

At this time, the PSU HRPP does not require Continuing Review (CR) submissions or documentation of a CR for External IRB studies. Please consult with the External IRB for CR submission requirements.

Request to Serve (R2S) as the Reviewing IRB 

While the processes for PSU to serve as the Reviewing IRB are still under development, we have started to offer this option when the research meets all the following criteria: 

  • The federally funded multi-site/cooperative project has five or less domestic sites that are engaged in non-exempt human subject research. 

  • All Relying Sites have or will sign on to the SMART IRB Master Common Reciprocal Institutional Review Board Authorization Agreement. 

Requests for the PSU IRB to serve as the Reviewing IRB should be submitted well in advance of any funding applications where a single IRB plan is needed. Investigators seeking an R2S should complete a Reliance Request Form. This form must be completed PRIOR to a submission in CATS IRB. Penn State’s HRPP CANNOT guarantee their willingness to act as the Reviewing IRB without the submission of this form. 

Investigators anticipating the need for a single IRB, and whose research does not fit the above criteria, should plan to use a commercial IRB or another accredited institution’s IRB that has the capacity for such large scale review. NOTE: PSU can still be the prime awardee of a grant and rely on an external IRB. 

As per the NIH FAQs, “recipient institutions have the flexibility to develop their own fee structures for single IRB costs”. If the PSU HRPP agrees to serve as the Reviewing IRB and sIRB fees apply, a letter of support will be provided, which provides a direct cost estimate (included as line item in budget) for the sIRB review fees to be charged to your award over the life of the project. The charges included in this estimate are for the additional costs incurred by providing external IRB review for other sites and are in addition to the indirect costs that cover IRB review at PSU for PSU researchers. 

R2S submissions in CATS are structured differently than projects undergoing local review. If the funding is awarded, the PI and lead coordinator(s) must schedule a meeting with the reliance team in order to discuss submitting your R2S in CATS. 

NOTE: The PSU study team for an R2S is responsible for facilitating communication between the PSU HRPP and the Relying Sites. The PSU study team must ensure that the relying sites are familiar with Penn State policy, such as RNI reporting timelines. The PSU study team is also responsible for submitting on behalf of all Relying Sites in CATS, including future continuing reviews, modifications, and RNIs. Study teams should consider allocating additional resources for administrative staff support in their grant applications. See the ‘SMART IRB Overall PI Checklist’ for guidance on the responsibilities of the study team for an R2S. 

SMART IRB Resources

SMART IRB is an initiative developed under an award from the National Center for Advancing Translational Science (NCATS) of the National Institutes of Health (NIH) to support single IRB review in facilitation of multi-site human subjects research.

The Penn State HRPP signed on to the SMART IRB Agreement as a Participating Institution. Using the SMART IRB Agreement as the ‘Reliance Agreement’ is an option if the other Participating Institutions have signed on and also agree to use the SMART IRB Agreement for a given study. A decision to use the SMART IRB agreement is made on a study-by-study basis by each Participating Institution.

Investigators are advised to visit the Resources section of the SMART IRB website for template documents that may be useful in the reliance process, including templates for the sIRB section of a grant application:

Using SMART IRB agreement does NOT replace or negate the internal submission process at Penn State regardless of whether Penn State is the Reviewing IRB or relying on an external IRB. Investigators should never assume that the agreement can or will be used for a given study or convey to others, including a funding agency, that the agreement will be used, without explicit documented agreement from each Participating Institution. NOTE: There are currently three listings for Penn State as participating institutions signed onto SMART IRB, please be sure to select the appropriate institution:

  • Penn State College of Medicine
  • The Pennsylvania State University [covers University Park and all other campus locations except the Penn State College of Medicine]