I: Background and Purpose

The UCR IACUC oversees and evaluates all aspects of animal care and use. All animal research at UCR requires an IACUC-approved animal use protocol (AUP) that has been reviewed by the IACUC to ensure that the criteria described in the PHS Policy¹, the Animal Welfare Regulations (AWRs) ², and the Guide for the Care and Use of Laboratory Animals (Guide)³ are met. In its review of proposals, the IACUC’s primary responsibility is to ensure animal welfare, while facilitating compliance with applicable laws, regulations, and policies consistent with the performance of appropriate and productive scientific endeavors.

This policy describes the submission and review process for new protocols, 3-year reviews, and amendments (revisions) to existing protocols.

II: Related policies

·         529-225: Custom Antibody Production Using Animals at Off-Campus Facilities

·         529-271: Authority of the Attending Veterinarian

·         529-343: Substitution or Addition of Mouse Strains

Definitions

III: Policy

1.       All vertebrate animal use in research or teaching at UC Riverside must be included in an approved AUP, including the use of animals in field research, breeding programs, or use of animals in the classroom or non-classroom instruction. Purely observational studies (animals and their environment are neither manipulated nor intentionally disturbed by the researcher or at the request of the researcher) do not require review or approval.

2.       Protocols are automatically reviewed by Full Committee Review (FCR) when the protocol or amendment involves any of the following criteria:

a.       Pain category E procedures (unrelieved pain or distress).

b.       Procedures that introduce a new, higher-level pain category.

c.       Major survival surgery or addition of a survival procedure to a previously non-survival protocol.

d.       Prolonged and unusual physical restraint of unanesthetized animals (a restraint that lasts longer than 15 minutes should be considered “prolonged restraint.” However, the length of time that could lead to distress in an animal will vary depending on the species, type of restraint used, activities performed on the animal, etc.).

e.       Fluid/food regulation (fasting prior to surgery or other procedures that require a period of = 24 hours without access to food or water is not considered fluid/food regulation.)

f.        Death as an endpoint.

g.       Request for an exception to any UCR IACUC Policy or the Guide for the Care and Use of Laboratory Animals (NRC, 2011).

h.       Use of a neuromuscular blocking agent.

3.       Any change to a protocol must be submitted as an amendment to an AUP. Amendments are processed by Full Committee Review (FCR), Designated Member Review (DMR), Veterinary Verification and Consultation (VVC), or administrative approval (AA), depending on the nature of the proposed revision. All review procedures are described in section V.

4.       No member may participate in the IACUC review or approval of an activity in which that member has a conflicting interest (e.g., is personally involved in the activity) except to provide information requested by the IACUC, nor will a member who has a conflicting interest contribute to the constitution of a quorum, in accordance with federal regulations.

5.       An IACUC quorum is a majority of the total number of voting members of the IACUC. A majority vote of the quorum present at a convened meeting is required to conduct AUP reviews and IACUC business. No proposed changes may be implemented until the amendment is approved by the IACUC.

IV: Submission and Pre-review

All AUPs are submitted electronically to the IACUC Office using Kuali. Approval of an AUP is for three years. After which, a renewal is submitted. All three-year renewals and new AUPs must undergo a pre-review. The pre-review is performed by the Campus Veterinarian (CV) and members of the IACUC Office. During the pre-review, comments are made, and modifications may be requested. Once addressed, the pre-review is completed, and the protocol is prepared for IACUC review.

Amendments to AUPs do not require a pre-review unless:

1. the changes require the AUP to be reviewed by FCR as outlined in section III.2

2. addition of another animal species

3. addition of a procedure that may increase pain and distress as determined by the CV  

Hazard Review

Use of hazardous agents (controlled substances, infectious agents, carcinogens, toxic chemicals, noxious gases including volatile anesthetics, radioisotope materials, tumor cells, and tissues, sera, or other biologics that may contain infectious agents) in laboratory animals will be reviewed by the appropriate Environmental Health and Safety (EH&S) officer. This review can occur during the pre-review or IACUC review stage.

V: Protocol Review Process

There are only two valid methods of IACUC review allowed by PHS Policy and the Animal Welfare Regulations: (1) full-committee review (FCR) by a convened quorum of the members of the IACUC, or (2) designated member review (DMR) by one or more members.

FCR takes place at a convened meeting with at least a quorum of the members present.  For each AUP, the IACUC has the authority to approve, require modifications (to secure approval), withhold approval, or defer until a future meeting. Determination of the outcome is by a simple majority of the members present.

DMR may only be utilized after all members have been provided the opportunity to call for full-committee review. The IACUC members have three (3) business days to review a submitted AUP to call for FCR. If any member requests FCR, that method must be used. If not, the IACUC Chair appoints one or more qualified IACUC members to serve as the designated reviewer(s). Designated review may result in approval, a requirement for modifications (to secure approval), or referral to the full committee for review. Designated review may not result in withholding of approval. If modifications to the protocol are required in order to secure approval, the AUP is returned to the PI to incorporate those modifications into the protocol and resubmit for review by the DMR.

DMR after FCR:  In cases where an AUP has undergone review at a Full Committee meeting, but the IACUC requires modifications in order to approve, OLAW has provided the following guidance, with which the USDA concurs:

All IACUC members agree in writing in advance that the quorum of members present at the FCR meeting may decide by unanimous vote to use DMR after FCR when modifications are needed to secure approval. However, any member of the IACUC may, at any time, request to see the revised protocol or amendment and/or request FCR for the protocol or amendment.

• “In advance” means that this policy must be approved by the IACUC prior to the first meeting at which it is used.
• “In writing” means that the policy and procedures must be written down and documented in the IACUC’s permanent records (e.g., IACUC meeting minutes) as having been established by unanimous agreement of all Committee members. Members are not required to physically sign the policy.
• New IACUC members will be trained in the process, but do not have to endorse the Policy for it to remain in effect.

3-Year (triennial) Review: Per PHS Policy, a complete de novo review of each current IACUC protocol is required once every three years.  Notices are sent to investigators regarding an upcoming expiration. Notices clearly convey to investigators that federal regulations do not allow protocol extension. At the triennial review, PIs of ongoing projects are required to submit a renewal to their AUP. No vertebrate animal activities are allowed beyond expiration unless an AUP renewal has been reviewed and approved.

VI: Amendments to AUPs

Any modification to a protocol must be submitted by the PI electronically as an amendment/revision to the AUP. The proposed changes may not be implemented until the amendment/revision is approved by the IACUC.

Modifications to an approved AUP will be processed by FCR, DMR, Veterinary Verification and Consultation (VVC), or administrative approval, depending on the nature of the proposed revision. The IACUC Office will review the proposed revision and classify it as “significant” or “minor” based on the following criteria:

1.       Significant changes that must be approved by one of the valid IACUC approval methods (DMR or FCR), include changes:

a.       from non-survival to survival surgery;

b.       resulting in greater pain, distress, or degree of invasiveness;

c.       in housing and or use of animals at a location that is not part of the animal program overseen by the IACUC;

d.       in species;

e.       in study objectives;

f.        in Principal Investigator (PI); and

g.       that impact personnel safety.

2.       Certain significant changes may be handled administratively according to IACUC-reviewed and -approved policies in consultation with a veterinarian authorized by the IACUC (VVC).   Consultation with the veterinarian must be documented. The veterinarian may refer any request to the IACUC for review for any reason and must refer any request that does not meet the parameters of the IACUC-reviewed and -approved policies. VVC may be used for:

a.       Changes to anesthesia, analgesia, or sedation.

b.       Addition or replacement of a euthanasia method that is acceptable (or conditionally acceptable when those conditions are met) according to the AVMA Guidelines for the Euthanasia of Animals.

3.       A significant change that may be handled administratively without additional consultation or notification, according to this IACUC-reviewed and -approved policy, is an increase of not more than 10% in previously approved animal numbers.

4.       Minor changes that may be handled administratively without IACUC-approved policies, consultations, or notifications include:

a.       Correction of typographical errors.

b.       Correction of grammar.

c.       Contact information updates.

d.       Change in personnel other than the PI (there will be an administrative review to ensure that all such personnel are appropriately identified, adequately trained and qualified, enrolled in occupational health and safety programs, and meet other criteria as required by the IACUC).

e.       Addition/change of a funding source.

f.        Removal of a proposed experiment from a protocol.

g.    Addition of a housing or procedure room that has been previously approved by the IACUC;

VII: Protocol and amendment withdrawals

Protocols and amendments will be considered withdrawn by the PI when:

• The PI requests the withdrawal of the AUP or amendment in writing.

• One year after the last response from the PI.

• Amendments will be considered withdrawn when the associated AUP expires.

References

1.       Public Health Service, Policy on Humane Care and Use of Laboratory Animals, Office of Laboratory Animal Welfare, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD.

2.       Animal Welfare Act Regulations 9 CFR §2.31

3.       National Research Council. 2011. Guide for the Care and Use of Laboratory Animals: Eighth Edition. Washington, DC

4.       The National Academies Press AVMA Guidelines for the Euthanasia of Animals (most current edition).

5.       NIH Guide Notice NOT-OD-14-126 (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-14-126.html)

6.       OLAW Webpage Significant Changes (https://olaw.nih.gov/guidance/significant-changes.htm)

7.       Frequently Asked Questions (FAQs) on PHS Policy, http://grants.nih.gov/grants/olaw/faqs.htm#641, Protocol Review, FAQ D19, “May an IACUC use designated member review (DMR) to review an animal study protocol subsequent to full committee review (FCR) when modifications are needed to secure approval?”

Approved: 12/16/2019; 9/20/2021; 7/10/23