Protocol Review Resources

View the Animal Study Proposal

1. Administrative Data
2. Animal Requirements
3. Transportation
4. Study Objectives
5. Rationale for Animal Use
6. Description of Experimental Design and Animal Procedures
7. Surgery
8. Pain or Distress Classification and Consideration of Alternatives
9. Anesthesia, Analgesia, Tranquilization, Other Agents
10. Methods of Euthanasia or Disposition of Animals at End of Study
11. Hazardous Agents
12. Biological Material/Animal Products for Use in Animals
13. Genetically Engineered Animals
14. Exemptions from Environmental Enrichment for Nonhuman Primates or Exercise for Dogs
15. Field Studies
16. Special Concerns or Requirements of the Study
17. Principal Investigator Certifications
18. Concurrences
19. Final Approval

• Appendix 1 - USDA Classifications and Examples
• Attachment 1 - Explanation for USDA Classification E

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Significant Changes to Animal Activities

Introduction

The PHS Policy on Humane Care and Use of Laboratory Animals (Policy) (IV.C.1.) and Animal Welfare Regulations (9 CFR 2.31 (d) (1) (i)- (iv)) define the responsibilities of the IACUC regarding review and approval of proposed significant changes to animal activities. Changes to approved research projects must be conducted in accordance with the institution’s Assurance, the US Department of Agriculture (USDA) Animal Welfare Act and Animal Welfare Regulations, and must be consistent with the Guide unless an acceptable justification for a departure is presented. Additionally, IACUCs are responsible for assuring that the changes to approved animal activities meet the requirements described in the PHS Policy IV.C.1.a.-g.

IACUC approval of proposed animal activities or significant changes to previously approved animal activities is granted after full committee review (FCR) or designated member review (DMR). Additionally, institutions may establish and IACUCs may approve policies (e.g., guidance documents, standard operating procedures, drug formularies) for the conduct of animal activities. These policies must be reviewed by the IACUC at appropriate intervals of no less than once every three years to ensure they are appropriate and accurate.

Significant Changes to Animal Activities Previously Approved by the IACUC

The IACUC has some discretion to use IACUC-reviewed and -approved 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. It is the IACUC’s responsibility to clearly define and communicate its policy for determining significance to investigators.

In brief, significant changes include changes that have, or have the potential to have, a negative impact on animal welfare (see paragraph 1., below). In addition, some activities that may not have a direct impact on animal welfare are also considered to be significant (see paragraphs 2. and 3., below).

In support of the use of performance standards and professional judgment and to reduce regulatory burden, IACUC-reviewed and -approved policies (e.g., guidance documents, standard operating procedures, drug formularies) for the conduct of animal activities may be used for the administrative handling of some significant changes according to the following considerations: 

1. Significant changes described in 1.a.-g., below, must be approved by one of the valid IACUC approval methods described in the PHS Policy IV.C.2., that is FCR or DMR, including changes:
   1. from nonsurvival to survival surgery;
   2. resulting in greater pain, distress, or degree of invasiveness;
   3. in housing and or use of animals 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.
2. The specific significant changes described in 2.a.-c., below, may be handled administratively according to IACUC-reviewed and -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-reviewed and -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. This includes changes in:
   1. anesthesia, analgesia, sedation, or experimental substances;
   2. euthanasia to any method approved in the AVMA Guidelines for the Euthanasia of Animals (PDF - 1.4 MB); and
   3. duration, frequency, type, or number of procedures performed on an animal.
3. A significant change that may be handled administratively according to an existing IACUC-reviewed and -approved policy without additional consultation or notification is an increase in previously approved animal numbers (PHS Policy IV.D.1.a.)

Other Changes

1. Changes that may be handled administratively without IACUC-approved policies, consultations, or notifications include:
   1. correction of typographical errors;
   2. correction of grammar;
   3. contact information updates; and
   4. 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 
   5. qualified, enrolled in occupational health and safety programs, and meet other criteria as required by the IACUC.)
2. Investigators may use fewer animals than approved. This does not require IACUC approval, notification, consultation, or administrative handling.

The USDA Animal and Plant Health Inspection Service has reviewed and concurs with this guidance.

Helpful Resources & References

• Guidance on Significant Changes to Animal Activities: OLAW Special Seminar, August 21, 2014
• Implementing Guidance on Significant Changes: One Institution's Experience: OLAW Online Seminar, September 8, 2016
• NOT-OD-14-126: Guidance on Significant Changes to Animal Activities

Policies and Laws

PHS Policy IV.B.6.: As an agent of the institution, the IACUC shall with respect to PHS-conducted or supported activities...review and approve, require modifications in (to secure approval), or withhold approval of those PHS-conducted or supported activities related to the care and use of animals as specified in IV.C.

PHS Policy IV.B.7.: As an agent of the institution, the IACUC shall with respect to PHS-conducted or supported activities...review and approve, require modifications in (to secure approval), or withhold approval of proposed significant changes regarding the use of animals in ongoing activities

PHS Policy IV.C.2.: Prior to the review, each IACUC member shall be provided with a list of proposed research projects to be reviewed. Written descriptions of research projects that involve the care and use of animals shall be available to all IACUC members, and any member of the IACUC may obtain, upon request, full committee review of those research projects. If full committee review is not requested, at least one member of the IACUC, designated by the chairperson and qualified to conduct the review, shall review those research projects and have the authority to approve, require modifications in (to secure approval), or request full committee review of those research projects. If full committee review is requested, approval of those research projects may be granted only after review at a convened meeting of a quorum of the IACUC and with the approval vote of a majority of the quorum present. No member may participate in the IACUC review or approval of a research project in which the member has a conflicting interest(e.g., is personally involved in the project) except to provide information requested by the IACUC; nor may a member who has a conflicting interest contribute to the constitution of a quorum.

PHS Policy IV.C.3.: The IACUC may invite consultants to assist in the review of complex issues. Consultants may not approve or withhold approval of an activity or vote with the IACUC unless they are also members of the IACUC.

PHS Policy IV.D.1.a.: All Institutions: Applications and proposals (competing and noncompeting) for awards submitted to the PHS that involve the care and use of animals shall contain the following information: a. identification of the species and approximate number of animals to be used