Purpose

This policy defines and clarifies what constitutes an amendment for previously approved Institutional Animal Care and Use Committee (IACUC) protocols as well as describe the routes by which protocols and amendments are approved by the committee. Amendments are classified as either minor or significant. This policy is consistent with the Public Health Service Policy on Humane Care and Use of Laboratory Animals (PHS Policy), the Animal Welfare Act and Animal Welfare Act Regulations (AWA) and guidance published from the NIH Office of Laboratory Animal Welfare (OLAW).

Owing to the great diversity of research performed at the university, it is not possible for the IACUC to anticipate all of the changes that investigators might potentially make to approved protocols and provide an exhaustive listing of those considered significant and minor. When in doubt, please contact the IACUC or Animal Welfare Services (AWS) for guidance.

Scope

All university faculty, researchers, staff and students who use live vertebrate animals for research, teaching, testing, or exhibition.

Person Responsible for Policy

Stephanie Womack, Director of Animal Welfare Services

Background/Definitions

Background

In accordance with the Animal Welfare Act (AWA), AWA regulations and the PHS Policy on Humane Care and Use of Laboratory Animals, all activities with live vertebrate animals must be covered under an active protocol, approved by the Institutional Animal Care and Use Committee. These federal regulations require that the IACUC at each institution “review and approve, required modifications in (to secure approval), or withhold approval of proposed significant changes regarding the use of animals in ongoing activities” (USDA AWRs 2.31 (c)(7), PHS Policy IV.B.7.). The PHS Policy (Section IV.C.1.) and the Animal Welfare Act Regulations (9 CFR 2.31 (d) (1) (i)- (iv) define the responsibilities of the IACUC regarding the review and approval of significant changes to animal activities by indicating that when reviewing any “proposed significant changes” the IACUC must “conduct a review of those components related to the care and use of animals and determine that the proposed research projects are in accordance with the PHS Policy.” Changes to approved animal activities must be conducted in accordance with the University of Oregon's PHS Assurance, the USDA Animal Welfare Act, and the Animal Welfare Regulations and must be consistent with the Guide for the Care and Use of Laboratory Animals (Guide) and meet the requirements of the PHS Policy. Policies pertaining to the review processes must be IACUC approved before implementation.

For significant changes to animal activities previously approved by the IACUC, the IACUC usually uses either a Full Committee Review (FCR) or Designated Member Review (DMR) process. However, the IACUC has some discretion to use IACUC-approved policies to define what it considers a significant change, or to establish a mechanism for determining what is a significant (major) change or a non-significant (minor) change on a case by case basis, as well as to determine the appropriate review process for significant changes as long as the IACUC is compliant with PHS Policy (Section IV.C.1.a-g). One of the times when discretion may be used is allowing the use of Veterinary Verification and Consultation (VVC) approval process for specific and defined significant changes.

Definitions

Amendment

An amendment is any modification or change to an IACUC approved animal care and use protocol. Amendments may be classified by the IACUC as minor or significant.

Grace period

A period of three business days in which any member of the IACUC may review the submission and refer to full committee. The first day of grace period begins either that day when processed before 12:00PM PST or the next business day.

Minor Amendment

A minor amendment is one that typically has minimal to no effect on personnel safety, animal welfare or animal use. The scope of minor amendments is very narrow and its use is limited.

Significant Amendment

A significant amendment is a proposed change to an approved protocol that proposes an evolution to the study design often based on new scientific, protocol specific information or animal welfare. It is one which substantially alters animal use from that originally approved in the protocol, has the potential to increase animal pain, distress, or discomfort, or which impacts personnel safety.

Methods of Review

Changes to an approved IACUC protocol must be reviewed by the IACUC using one of the following methods:

• Full Committee Review (FCR): A quorum of the IACUC members reviews the proposed amendment at a convened meeting. The Full Committee can approve, require modifications to secure approval, or withhold approval. Approval requires vote by the majority of the quorum present to approve the amendment. DMR subsequent to FCR may be used in accordance with OLAW's guidance: NOT-OD-035:
  • If all members of the IACUC are present at a meeting, the committee may vote to require modifications to secure approval and have the revised research protocol reviewed and approved by designated member review (DMR), or returned for FCR at a convened meeting.
  • If all members of the IACUC are not present at a meeting, the committee may use DMR subsequent to FCR according to the following stipulations:
  • All IACUC members agree in advance in writing that the quorum of members present at a convened meeting may decide by unanimous vote to use DMR subsequent to FCR when modification is needed to secure approval. However, any member of the IACUC may, at any time, request to see the revised protocol and/or request FCR of the protocol. Unanimous approval of this IACUC policy by the committee every three years constitutes agreement in advance in writing.
• Designated Member Review (DMR): Requires each IACUC member be emailed with a list of proposed research projects and PI to be reviewed with access to the full, written protocol via online links. If no member requests Full Committee review of the amendment with the three day grace period, at least one voting IACUC member reviews and determines if the amendment is approved, requires modifications to secure approval, or requests FCR. The designated reviewer is appointed by the IACUC Chair or their designee.
• Veterinary Verification and Consultation (VVC): A veterinarian, such as the Attending Veterinarian, is authorized by the IACUC to review and verify that the proposed amendment conforms to approved IACUC policies or other IACUC-approved specific source documents. Upon written verification via the electronic protocol system by the authorized veterinarian the amendment is approved. The veterinarian can refer any amendment to the IACUC for review (DMR or FCR) for any reason and must refer any request that does not meet the parameters of the IACUC-approved policies or IACUC-approved specific source documents.
• Administrative Review (AR): Performed by the Animal Welfare Services Director or designee based on IACUC-approved policies/procedures without IACUC consultations or notifications.

Policy

FCR or DMR

The following significant changes described below must be approved by either FCR or DMR:

• Change in PI
• Change in study objective or new phase of the study
• Change in species
• Addition of a new genetically modified animal
• Addition of a new procedure
• Addition of food and/or fluid control
• A change from non-survival surgery to survival surgery
• Change resulting in greater pain, distress, or degree of invasiveness
• Addition of surgical procedures
• Change from single to multiple major procedures
• Protocol changes that may escalate the previously approved US Department of Agriculture (USDA) Pain Category and/or increase the duration of pain, discomfort, or distress of the animal
• Addition of new experimental substances/drugs or hazardous agents that belong to a new class of drugs or agents.
• Change from pharmaceutical grade to non-pharmaceutical grade substances as long as recommendations from OLAW guidance on the use of non-pharmaceutical grade substances are considered
• Changes that impact personnel safety (e.g., change in biosafety level, addition of hazardous agents)
• Changes in housing and or use of animals in a location that is not part of the animal program overseen by the IACUC (i.e. satellite housing)
• An increase in animal numbers by more than 50%
• Addition of exemptions, exceptions, or deviations from the PHS Policy, Animal Welfare Act/Regulations, the NIH Guide for the Care and Use of Animals, or IACUC-approved policies
• Addition of Cooperative Research
• Any significant change not described in VVC or administrative review below

VVC

The following significant changes described below may be handled according to IACUC-approved policies in consultation with a veterinarian authorized by the IACUC. The veterinarian is not conducting DMR, but is serving as a subject matter expert to verify that compliance with the IACUC-approved policy is appropriate for the animals in this circumstance. 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. The VVC process cannot be used for any of the changes listed above in the FCR or DMR category:

• Change in anesthesia, analgesia and sedation protocols that use referenced dosages for the species such as those listed in the UO Anesthesia for Laboratory Animals  policy. Reference material may also include textbooks (such as Harkness and Wagner’s Biology and Medicine of Rabbits and Rodents; Flecknell’s Laboratory Animal Anesthesia; Plumb’s Veterinary Drug Handbook; Hawk and Leary’s Formulary for Laboratory Animals; Fowler’s Zoo and Wildlife Medicine; Lumb and Jones Veterinary Anesthesia and Analgesia; Quesenberry and Carpenter’s Ferrets, Rabbits and Rodents Clinical Medicine and Surgery; ); journal publications (peer reviewed from PubMed and CAB database)
• Change in euthanasia to a method approved in the UO Euthanasia Policy or those approved in the American Veterinary Medical Association (AVMA) Guidelines for the Euthanasia of Animals as either “Acceptable” or “Acceptable with Conditions” as long as the AVMA-stipulated conditions are met for that species
• Change in acclimatization period following receipt of animals.
• Changes in experimental substances that are known to not increase invasiveness or expected adverse outcomes or increase hazards to personnel
  • Change of drug that does not create a new change in animal health status
  • Change of diet that does not create a new change in animal health status
  • Change to a similar or less invasive method of drug administration including frequency (no greater than three times per day) & route (limited to SC, IP, IV, PO)
  • Change of volume within the guidelines described in Diehl et al, Journal of Applied Toxicology 21: 15‐23 and Turner et al, Journal of the American Association for Laboratory Animal Science 50 (5): 600‐613,
• Changes in the duration, frequency, type, or number of procedures performed as long as those procedures have been previously approved in the protocol. For example:
  • Blood collection site, volume, or frequency in accordance with UO Blood Collection Methods and does not exceed guidelines published by Diehl et al. A good practice guide to the administration of substances and removal of blood, including routes and volumes. J App Tox. 2001; 21:15-23
  • Administration volumes and routes within the guidance provided in Diehl et al. A good practice guide to the administration of substances and removal of blood, including routes and volumes. J App Tox. 2001; 21:15-23
  • Change in food and/or fluid restriction as defined by the UO policy on Food or Fluid Regulation and described in the protocol
  • Change or additional breeds, strain, sex, age, or weight of animals of the approved species
  • Changes to husbandry requirements (e.g., space, weaning, food type/source, light-cycle) if within the recommendations of the of the Guide and/or Animal Welfare Act/Regulations
  • Change in final disposition of animal(s) in accordance with IACUC-approved policies
  • Change in humane-endpoints which result in no change or reduction of the potential level of pain, distress, or discomfort
  • Change in non-invasive imaging technique
  • Peri-operative or peri-procedural monitoring or supportive care
  • Modifications to previously approved surgeries that do not increase the invasiveness or expected adverse outcomes; includes changing from survival to non-survival surgery
  • Timing of euthanasia as long as there is no increase in pain, distress, or discomfort
  • Identification or genotyping within the  TeACS Rodent Identification Methods SOP
  • Change from non-pharmaceutical-grade to pharmaceutical-grade substance(s)
  • Other changes to approved procedures performed on an animal contingent upon them not exceeding guidelines or other references approved by the IACUC

Administrative

The following significant and minor changes described below may be handled administratively by the Director of Animal Welfare Services or designee. 

Changes that require the PI to submit an amendment for administration include the following examples:

• Increase in animal numbers ≤ 50% for non-USDA regulated species of previously approved animal numbers (no more than three times for the life of the protocol subsequent request are significant changes). The original rational for the numbers of animals should continue to support the increase in percent being requested. If not, a revised rationale is required
• Change in personnel, other than the PI. There must 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
• Change in animal use location or animal housing to a centrally managed area or previously IACUC-approved area
• Change in site of non-surgical animal procedures as long as animals are maintained there for less than 12 hours
• Change in source of animals. Contact IACUC (iacuc@uoregon.edu) for standard operating procedures on Procurement of Animals, Receiving Animals and Request to Import Animals from Other Institutions
• Change in manufacturer of substance as long as there is no change in purity, sterility, etc.
• Change in method of sterilization of materials or instruments as long as described in procedure.
• Change in funding information
• Changes in controlled substance source or registration
• Deletion of information (e.g., species, procedures, locations)

Examples of changes that do not require review or approval: 

Note: Changes below may be done without review or verification provided that these changes do not overlap any category above. These changes may be submitted via an amendment and approved administratively.

• Use of fewer animals than approved or omission of experiments, experimental procedures or surgeries (this does not include withholding anesthetics, analgesics, sedatives, or other required pain reliving measures)
• Change to sterile caging
• Physical changes that reduce pain, distress, trauma or infection such as changing to a smaller needle or implant, an earlier endpoint, making a smaller incision, using a less traumatic surgical approach, leaving an animal in its familiar environment for a procedure rather than taking it elsewhere, achieving greater tissue apposition during surgery or using sterile gowns for rodent surgery
• Changes that increase human safety that do not impact animal welfare or research objectives such as using additional personal protective equipment or less of a toxic or noxious substance.
• Replacement of animals that die or are euthanized before research manipulations occur
• Use of discarded carcasses, tissues, organs, blood, eggs, etc. from animals
• Correction of typographical errors
• Correction of grammar
• Contact information updates
• Change in protocol title
• Removal of personnel

Process

• FCR vs. DMR by the Institutional Animal Care and Use Committee (IACUC)
  • Protocols and amendments submitted to the Institutional Animal Care and Use Committee (IACUC) for review can be reviewed via two methods, a Designated Member Review (DMR) and a Full Committee Review (FCR). The method used for the review is determined by the timing of protocol submission and consensus of the committee. The two methods for protocol review are described below.
  • Protocol Review via Designated Member Review (DMR)
    • Proposed activities involving animals are reviewed as efficiently as possible to facilitate the research or teaching effort and funding agency needs. Some Animal Use Protocols undergo full committee review (FCR) at a convened meeting of the IACUC; however, an alternate manner of review and approval for protocols and amendments may be conducted via designated member review (DMR). DMR may provide a shorter response time for the investigators and decreased time investment by all members of the IACUC while still providing a robust review process.
    • DMR Procedure
      • DMR is conducted by a subset of the IACUC members and occurs outside a convened meeting. The DMR process can be used to review and approve amendments and standard procedures.
      • Category ‘E’ procedures and protocols are designated to full committee review unless agreed upon by a quorum at a full committee meeting.
      • Triennial reviews and new protocols are reviewed by the full committee whenever possible; Timing constraints or funding concerns may justify the use of DMR for these protocol types.
      • The amendment or protocol will be sent out to all IACUC members by the IACUC Administrator for review. The IACUC members have 3 days to respond to request FCR. No response is considered an agreement to review by DMR. Any IACUC member may, at any time, call the protocol or amendment for FCR that has been sent to DMR.
      • If no member calls the submission for Full Committee Review (FCR), the IACUC Chair or their designee will appoint one or more qualified reviewer(s) for DMR.
        • The appointed reviewer(s) can make the following determinations:
          • Approve the submission as submitted
          • Request modifications to secure approval: If modifications are requested to secure approval, the original designated reviewers will review the modified protocol/amendment.
            This is the most common determination. This process may require more than one round of modification requests from the appointed reviewer(s) before final approval of the protocol.
          • Request FCR of the protocol: The protocol/amendment would be reviewed at the next convened meeting.
          • In addition, with a unanimous vote of the quorum present at a convened meeting, the Committee can vote to have a DMR review and approve protocols/amendments for final protocol approval after modifications requested in the FCR have been addressed in the revised protocol/amendment.  In this case, one or more designated reviewers will review the modified protocol/ amendment following the convened meeting once the revised protocol has been resubmitted.
      • Expedited DMR Review
        • When warranted (extenuating deadlines, protocol expiration dates) protocols may be subject to expedited review. All IACUC members must unanimously agree to expedited DMR review. Approval may be obtained verbally or in writing. No reply does not constitute approval.
        • All members of the IACUC are provided with the PI name, protocol name, and link to documentation. Upon unanimous approval for expedited review a designated reviewer is chosen by the IACUC Chair or their designee. Any member of the committee may refer the submission to full committee review.
        • The designated reviewer is given an accelerated timeline for review based on previously agreed upon time availability.
    • Protocol Review via Full Committee Review (FCR)
      • Protocols and amendments may be reviewed at a Full Committee Meeting (FCR). Members of the IACUC may request that protocols and amendments be reviewed via FCR instead of DMR at any time.
      • FCR Procedure
        • Prior to the monthly meeting, at least one reviewer is assigned as primary reviewer for each of the submissions for that meeting. All committee members are expected to review all protocol submissions, however, the primary reviewer is responsible for presenting the protocol to the Committee for discussion at the meeting.
        • After the protocol is discussed at the meeting, the following determinations are possible:
        • Recommended for approval: The Committee approves the submission as it was submitted.
        • Modifications required to secure approval: Minor questions and/or clarifications must be resolved by the protocol’s Principal Investigator (PI) to secure final protocol approval. The committee members present at the meeting must decide by unanimous vote to use DMR to review the submission after it has been modified and resubmitted. This process may require more than one round of modification requests from the appointed reviewer before final approval of the protocol.
          This is the most common determination.
        • Tabled: The submission is written in such a way that the Committee cannot complete the review because there are significant omissions and questions that must be resolved to secure approval. A Tabled ruling requires that the revised protocol be resubmitted as a new protocol for FCR at a convened meeting.
        • Withhold Approval: If the PI and the IACUC cannot agree on fundamental aspects of the protocol, such as protocol design and animal welfare issues, the Committee may withhold approval. The PI would receive a letter from the IACUC explaining why approval is being withheld.
        • Protocols/amendments that involve complicated, invasive, or novel procedures and protocols that involve significant pain and distress often will be reviewed at a full committee meeting and not in a DMR. The decision to hold a submitted protocol for FCR is the Committee’s prerogative. In addition, protocols involving a principal investigator who has not previously submitted a protocol to the University of Oregon IACUC should anticipate FCR of his/her first submitted protocol.
        • Time required for FCR and DMR
        • The PI should anticipate that a submitted protocol may require a month to several months to complete the protocol review and approval process. Please plan accordingly.
        • Archived Submissions
        • Protocols are reviewed by the Committee with the expectation that the PI will address the requested revisions/modifications and resubmit the protocol promptly. Protocols requiring modifications that are not resubmitted within 60 days of receipt of the Committee’s comments from the initial review will be archived. An archived protocol that is resubmitted after 60 days will be handled as a new submission
    • VVC
      • The authorizing veterinarian will provide written verification via the electronic protocol system to the IACUC office (e.g., email), within three business days, for inclusion into the protocol file. If the protocol amendment is associated with an electronic protocol, the authorized veterinarian will make a comment in the protocol as part of the VVC approval process. This documentation will state the changes that were verified and approved following consultation with the principal investigator (PI) or designee. An approval letter will be sent to the PI and their designee. Written documentation is available in the electronic file system. 

Approvals

Effective date: 03/13/2025