This policy is intended to clarify the process for determining what constitutes a “significant change” to an approved ARC protocol, and to describe the process for review and approval of these activities.
Statutory Basis
Federal regulations require that the Institutional Animal Care and Use Committee (IACUC) at each institution “review and approve, require 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).
PHS Policy IV.C.1 requires that when reviewing any “proposed significant change,” the IACUC “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. In making this determination, the IACUC shall confirm that the research project will be conducted in accordance with the Animal Welfare Act insofar as it applies to the research project, and that the research project is consistent with the Guide [Guide for the Care and Use of Laboratory Animals] unless acceptable justification for a departure is presented.” [1]
IACUC approval of proposed animal activities or significant changes to previously approved animal activities is generally only granted after full committee review (FCR) or designated member review (DMR). However, thanks to guidance from the NIH Office of Laboratory Animal Welfare (OLAW), the IACUC has some discretion to use local policies to define what it considers a significant change, or to establish a mechanism for determining significance on a case-by-case basis in accordance with the PHS Policy IV.C.1.a.-g.
According to OLAW, “…significant changes include changes that have, or have the potential to have, a negative impact on animal welfare. In addition, some activities that may not have a direct impact on animal welfare are also considered to be significant.” In an effort to reduce regulatory burden, and acknowledging the roles of professional judgment and performance standards, OLAW also allows institutions to develop policies to allow administrative handling of some significant changes. See the OLAW Guidance on Significant Changes to Animal Activities for more information.
ARC Review of Significant Changes
With the exceptions outlined by OLAW, the ARC must review all proposed significant changes using either the Full Committee Review (FCR) or Designated Member Review (DMR) processes.
Significant changes that must be reviewed by FCR or DMR include changes:
- from non-survival to survival surgery;
- resulting in greater pain, distress, or degree of invasiveness;
- in housing and or use of animals in a location that is not part of the animal program currently overseen by the IACUC;
- in species;
- in overall study objectives;
- in Principal Investigator (PI);
- that impact personnel safety.
Investigators are advised to build flexibility into their protocols in order to minimize the likelihood that significant changes must be made to the protocol (e.g., including a maximum volume of blood to be collected, alternate methods of blood collection, a range of drug doses to be administered).
If a proposed significant change does not appear on the above list of changes requiring FCR or DMR, it may be eligible for an alternative method of review. At the discretion of the ARC Chair or Vice-Chair, the specific changes described below may be handled outside of the FCR and DMR processes:
- anesthesia, analgesia, sedation, or experimental substances, as detailed in the Formulary for Laboratory Animals (3rd edition) [2];
- euthanasia using any method approved in the most current version of the AVMA Guidelines for the Euthanasia of Animals;
- duration, frequency, type, or number of procedures performed on an animal as described in an approved ARC Policy, for example, the ARC Policies on Blood Collection from Laboratory Animals and Tissue Collection for DNA Extraction for Genotyping in Rodents;
- increase in previously approved animal numbers, so long as the increased number of animals requested is ≤50% of the number last approved via DMR or FCR.
The ARC Chair or Vice-Chair is empowered to review an increase in previously approved animal numbers (d). Changes described under a-c above will be reviewed by the ARC Chair or Vice-Chair in consultation with the authorized veterinarian. [3]
Review of Non-Significant Changes
Changes that are considered not significant may be reviewed by the ARC Chair or Vice-Chair, or authorized administrative staff in the Research Safety & Animal Welfare Administration (RSAWA) [4]; these changes include:
- personnel, excluding the PI;
- contact information;
- title of ARC protocol;
- funding; and
- housing and or use of animals in a location that is already part of the animal program currently overseen by the IACUC.
In all cases, the PI must submit an amendment describing the proposed changes and obtain ARC approval before implementing any changes to previously approved activities.
[1] Specific criteria that must be considered are set forth in PHS Policy IV.C.1.a.-g., USDA AWRs §2.31(d)(1)(i)-(xi), and USDA AWRs §2.31(e).
[2] The Formulary for Laboratory Animals (3rd edition) is available.
[3] The “authorized veterinarian” was selected by the ARC at a convened meeting on 6/8/2015 to serve as a subject matter expert in this circumstance. The individuals designated to serve in this capacity are a matter of record in the ARC office.
[4] The RSAWA staff authorized to perform administrative review of non-significant changes were selected by the ARC at convened meetings on 6/8/2015, 3/28/2016, 8/22/2016, 7/9/2018, and 2/28/2022, and are a matter of record in the ARC office.
Approved 3/28/11; Revised 6/8/15, 9/28/15, 4/24/17; Updated 3/28/16, 8/22/16, 7/9/18, 2/28/22