Key Dates

Related Announcements

• August 26, 2014 - Guidance on Significant Changes to Animal Activities. See Notice NOT-OD-14-126
• March 18, 2011 - Guidance to Reduce Regulatory Burden for IACUC Administration Regarding Alternate Members and Approval Dates. See Notice NOT-OD-11-053
• January 8, 2009 - Guidance to IACUCs Regarding Use of Designated Member Review (DMR) for Animal Study Proposal Review Subsequent to Full Committee Review (FCR). See Notice NOT-OD-09-035

Issued by

Office of The Director, National Institutes of Health (OD)

Purpose

Through this Request for Information (RFI), the NIH Office of Laboratory Animal Welfare (OLAW) seeks input on encouraging Institutional Animal Care and Use Committees (IACUCs) at Assured institutions to use existing flexibilities to streamline the review of protocols and significant changes.

Background

OLAW oversees animal activities at Assured institutions by the authority of the Health Research Extension Act of 1985 (HREA), the Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals (Policy), and memoranda of understanding with the National Aeronautics and Space Administration (NASA), National Science Foundation (NSF), and Department of Veterans Affairs (VA).

In response to the 21^st Century Cures Act, section 2034(d) and feedback from stakeholders, the NIH conducted a review of applicable regulations and policies for the care and use of laboratory animals to reduce the administrative burden on investigators while maintaining the integrity and credibility of research findings and protection of research animals. One of the actions identified in the resulting report, Reducing Administrative Burden for Researchers: Animal Care and Use in Research, encourages Assured institutions to use flexibilities that streamline review of protocols and significant changes, such as designated member review (DMR), DMR subsequent to full committee review (FCR), veterinary verification and consultation (VVC), and administrative handling of increases in previously approved animal numbers. These processes, when implemented correctly, maintain compliance, high standards of animal welfare, and the rigor of the IACUC review process.

Options for Review of Protocols and Significant Changes

IACUCs are required by PHS Policy IV.B.6.-7. to review funded or supported animal activities and proposed significant changes in ongoing activities related to the care and use of animals with a decision to approve, require modifications in (to secure approval) or withhold approval. The PHS Policy IV.C.2. and 9 C.F.R. 2.31(d)(2) of the Animal Welfare Regulations (AWRs) describe two methods of IACUC review of research activities involving animals FCR and DMR. Additionally, PHS Policy IV.C.5. and an amendment to the AWRs 2.31(d)(5) require the IACUC to conduct a complete review of each previously approved, ongoing activity at least once every three years.

FCR and DMR: FCR and DMR are equally valid methods of IACUC review for protocols and significant changes, recognizing that all IACUC members must be provided with the opportunity to call for FCR (see Protocol Review and FAQ D.3.). Any IACUC member may, at any time, request to see the revised protocol or request FCR. If FCR is requested, then the protocol must be reviewed by this method. The IACUC may discuss approved protocols and significant changes in future meetings as a form of continuing review or in response to animal welfare concerns.

The PHS Policy IV.C. and Animal Welfare Regulations (9 CFR 2.31 (d) (1) (i)- (xi)) define the responsibilities of the IACUC regarding review and approval of animal activities. Prior to the review, each IACUC member must be provided with a list of proposed research projects to be reviewed. Written descriptions of each research project must also be available to all IACUC members (PHS Policy IV.C.2.). In addition:

• The review must not be finalized until all members have had a reasonable opportunity to call for FCR, and FCR must be used if requested by any IACUC member (OPRR Reports 90-01).
• No member with a conflicting interest may participate in the IACUC review of that animal activity, except to provide information requested by the IACUC, nor may they contribute to the quorum.
• IACUC members may confer with outside consultants on complex issues (PHS Policy IV.C.3.). However, consultants may not approve or withhold approval of an activity or vote with the IACUC unless they are also members of the IACUC.

For both FCR and DMR, the use of alternate IACUC members may help to ensure timely review and approval of animal activities. However, alternates may only serve when the regular member is truly unavailable (e.g., out of the office, on sabbatical, travelling) (NOT-OD-11-053). The IACUC should have a procedure to identify when an alternate is serving, and which alternate is serving in place of a regular member for DMR, FCR, or other IACUC activities.

FCR: FCR may only be conducted at a convened meeting of a quorum of the IACUC, and a majority vote of the quorum present is required to approve, require modifications in (to secure approval), or withhold approval of any proposed animal activity (PHS Policy IV.C.2.).

DMR: If FCR is not requested, at least one member of the IACUC, designated by the chairperson and qualified to conduct the review, may review the research project and has the authority to approve, require modifications in (to secure approval), or request FCR (PHS Policy IV.C.2.). DMR may not result in withholding approval. Once members have declined to call for FCR, and the research project has been approved by DMR, no additional review by the IACUC is required.

DMR Subsequent to FCR: During the convened meeting for FCR, once the majority vote of the quorum present determines that modifications are required to secure approval, the revised research project must be reviewed using either FCR or DMR. DMR subsequent to FCR allows IACUCs to have the revised submission reviewed and approved by DMR instead of returning to FCR (see NOT-OD-09-035). When conducting DMR subsequent to FCR, the designated reviewer(s) must be selected by the chairperson and address all questions, concerns, and requested modifications agreed upon by the IACUC members at the convened meeting.

Implementing DMR subsequent to FCR is context-dependent, as outlined below:

• If all IACUC members are present at a convened meeting, they may unanimously vote to have the revised research protocol reviewed and approved by DMR.
  
• If all IACUC members are not present:
  • When there is an IACUC-reviewed and approved written policy on DMR subsequent to FCR in place, the quorum of members present at a convened meeting may decide by unanimous vote to use DMR subsequent to FCR. However, any IACUC member may, at any time, request to see the revised protocol and/or request FCR of the protocol.
  • When the IACUC lacks a written policy, the IACUC may use FCR or propose DMR. To use DMR, all members, including those absent from the meeting, must have the revised research protocol available and the opportunity to call for FCR. If FCR is requested, then the protocol must be reviewed by this method.

Additional Options for Significant Changes

Significant changes that have, or have the potential to have, a negative impact on animal welfare must be approved by FCR or DMR, and include changes:

1. from nonsurvival to survival surgery;
2. resulting in greater pain, distress, or degree of invasiveness;
3. in housing or animal use in a location that is not part of the animal program overseen by the IACUC;
4. in species;
5. in study objectives;
6. in Principal Investigator (PI); and
7. that impact personnel safety.

VVC: Specific significant changes to previously approved animal activities may be handled according to an IACUC-approved VVC policy that incorporates the following four required components:

1. IACUC-defined eligible significant changes, including but not limited to, changes in:
   • Anesthesia, analgesia, sedation, or experimental substances;
   • Euthanasia to any method approved in the AVMA Guidelines for the Euthanasia of Animals (approved means any acceptable method of euthanasia for a given species or, a method that is acceptable with conditions for that species provided all conditions are met); and
   • Duration, frequency, type, or number of procedures performed on an animal.
     
2. IACUC-approved references for each VVC-eligible significant change included in the IACUC policy, to set allowable parameters,
   
3. IACUC-authorized veterinarian(s) to verify, through consultation, that the requested significant change(s) are compliant with the VVC policy, and
   
4. A method to document the consultation and verification of the change in the protocol.

VVC may not be used to add a new procedure that was not previously approved on the protocol, nor does a standard operating procedure approved for other protocols justify the addition of a new procedure to a protocol using VVC.

Increase in Previously Approved Animal Numbers: An increase in previously approved animal numbers (PHS Policy IV.D.1.a.) is a significant change that may be handled administratively by an authorized individual(s), provided there is an IACUC-approved policy. The policy must:

• Specify the conditions when increases in animal numbers may be handled administratively;
• Identify the authorized individual(s) by title or name;
• Clearly define the limits of animal number increases; and
• Require that the study objectives and the rationale for using animals are unchanged by the increase. If the rationale or study objectives change, IACUC review by DMR or FCR is required.

OLAW is not requesting comments on the above background information. This information is for context only and provides the framework upon which the following described flexibilities can be implemented. OLAW will only consider comments regarding the information under the Information Requested section of the RFI.

The United States Department of Agriculture (USDA) Animal and Plant Health Inspection Service has reviewed and concurs with the guidance provided in this Notice.

Information Requested

OLAW is seeking input on encouraging the use of DMR, DMR subsequent to FCR, VVC, and administrative handling of increase in previously approved animal numbers. The following flexibilities may streamline these review processes and reduce administrative burden without compromising animal welfare and the rigor of the IACUC review process.

Proposed Guidance for Streamlining DMR

DMR, which does not require a quorum of the IACUC at a convened meeting, may reduce administrative burden and enhance review efficiency by decreasing the turnaround time for IACUC review and approval. The following flexibilities may be used with DMR:

1. The IACUC may determine a reduced, but reasonable, time frame agreed upon by the IACUC to obtain concurrence to call for FCR from all members or concurrence by silent assent once the full time has elapsed (e.g., three instead of seven business days).
   
2. Submissions may be routed for DMR to allow the DMR process to be initiated while the IACUC is provided time to call for FCR. However, the outcome of the review cannot be finalized until all IACUC members have been provided a reasonable time to call for FCR (OPRR Reports 90-01). If all voting members respond before the end of the predetermined time frame, and there are no requests for FCR, DMR may be finalized.
   
3. The IACUC may establish criteria for which some types of research or significant changes may be flagged for DMR. All members must be provided a reasonable time to call for FCR, but the DMR process may be initiated during that time. Only when there are no requests for FCR at the end of the predetermined time frame, may DMR be finalized.
   
   
   • Examples of criteria based on types of research:
     • Involve minimal or no pain or distress to the animal(s)
     • Utilize species not regulated by the USDA
     • Are minimally invasive (e.g., euthanasia for tissue harvest, breeding or holding protocols, injections, routine blood collection, minor surgery, non-survival surgery)
       
   • Examples of criteria based on significant changes:
     • Change in PI
     • Change or addition of species without a change in study objectives
     • Housing in a location that has not been previously approved by the IACUC
     • Addition of a procedure that does not result in greater pain, distress, or degree of invasiveness
     • Addition of anesthesia, sedation, or analgesia that will improve animal well-being
       
4. The IACUC chairperson may designate only one qualified member to conduct the review, which may reduce the burden associated with designating multiple reviewers because it eliminates the requirements that:
   
   • Reviewers must be unanimous in any decision.
   • Reviewers must review identical versions of the protocol.
   • If modifications are requested by any reviewer, then the other reviewers must agree to the modifications.
     
5. The IACUC has the flexibility to determine the best way for the chairperson to assign the designated reviewer, including creating a policy. The policy should accommodate future assignment changes for conflicts of interest or unavailable reviewers, while ensuring that the designated member is qualified to conduct the review. Using a rotational list of reviewers based on their expertise, and appointing a vice chairperson to assign reviewers in the chairperson’s absence are other mechanisms to increase efficiency.
   
6. Designated reviewers may refer to scientific-based publications in peer-reviewed journals or guidelines prepared by professional organizations (see OLAW FAQ D.17.) as an alternative to ad hoc consultants.
   
7. The IACUC may determine the best means of documenting the DMR process from review to approval (e.g., emails or forms).
   
8. Designated member approval does not require subsequent reapproval by the IACUC at a convened meeting.
   
9. The IACUC may expedite the three-year complete review of an ongoing protocol that is due to expire. This may only occur during extenuating circumstances, such as disasters impacting research or extended unplanned PI unavailability. The intent of this flexibility is to permit the continuation of research in accordance with PHS Policy IV.C.5.
   
   
   • The expedited review process must include the following parameters:
     • Members may agree to a shortened response time to call for FCR. If no member calls for FCR, the protocol may be reviewed by DMR (PHS Policy IV.C.2.).
     • The IACUC must have a policy describing a shortened approval period for ongoing activities (i.e., previously approved protocols due to expire) to extend only for the duration of the unplanned circumstances.
     • No significant changes are allowed using the expedited process. Any significant changes must be submitted and reviewed after the circumstances have resolved.
       

Proposed Guidance for Streamlining DMR subsequent to FCR

To avoid temporal delays and reduce burden, DMR subsequent to FCR provides the following flexibilities for IACUCs to have the revised protocol reviewed and approved:

1. Neither a convened meeting nor a vote is necessary to propose a DMR subsequent to FCR policy. Emails and forms are acceptable, though each member must be given the opportunity to provide their input in person or electronically prior to its approval. The policy may be implemented as soon as all members agree to it. New members must be informed of the policy and agree to its use.
2. Members are not required to sign the policy (either physically or electronically) and there is no requirement for a written statement at every meeting.
3. If an IACUC uses a primary reviewer during FCR, the IACUC chairperson may designate this reviewer for DMR subsequent to FCR and for any future proposed significant changes, provided no member calls for FCR.

Proposed Guidance for Streamlining VVC

The following flexibilities for VVC may be implemented:

1. IACUCs may authorize more than one veterinarian, who need not be an employee, to conduct VVC. If the veterinarian determines the requested change is consistent with the VVC policy and appropriate for the animals in question, it may go into effect immediately.
2. IACUCs may use established references (e.g., formularies, guidance documents, institutional policies, standard operating procedures) to set allowable parameters for each VVC-eligible significant change included in the VVC policy. This reduces the burden of developing references when established references that meet the needs of the IACUC are already available.
3. The IACUC has flexibility to determine the processing and documentation of VVC (e.g., emails or forms handled by any individual in the IACUC office, IACUC chairperson, or veterinarians).
4. Changes handled by VVC do not require subsequent reapproval by, or notification to, the IACUC.

Proposed Guidance for Streamlining Administrative Handling of Increase in Previously Approved Animal Numbers:

An increase in previously approved animal numbers (PHS Policy IV.D.1.a.) may be handled administratively according to an IACUC-approved policy. The following flexibilities may be implemented:

1. The increase may be expressed as a percentage, an exact number, or a number relative to the original number approved, and may be taxa-specific (e.g., a 10% increase in rodents).
2. The IACUC has flexibility to determine the most appropriate individuals and means of handling and documenting this process. (e.g., emails or forms handled by any individual in the IACUC office, IACUC chairperson, or veterinarians).
3. Changes handled administratively do not require subsequent reapproval by, or notification to, the IACUC.
   

How to Submit a Response

All responses to this RFI must be submitted electronically on the RFI webpage by 10/11/2023 at 11:59 PM ET. The comments may be made available on the OLAW website.

Responses to this RFI are voluntary and may be submitted anonymously. Please do not include any personally identifiable or other information that you do not wish to make public. Proprietary, classified, confidential, or sensitive information should not be included in responses. The Government will use the information submitted in response to this RFI at its discretion. The Government reserves the right to use any submitted information on public websites, in reports, in summaries of the state of the science, in any possible resultant solicitation(s), grant(s), or cooperative agreement(s), or in the development of future funding opportunity announcements. This RFI is for informational and planning purposes only and is not a solicitation for applications or an obligation on the part of the Government to provide support for any ideas identified in response to it. Please note that the Government will not pay for the preparation of any information submitted or for use of that information.

Inquiries

Please direct all inquiries to:

Office of Laboratory Animal Welfare (OLAW)
Telephone: 301-496-7163
Email: [email protected]