Table of contents
- 1. NRC Animal Care Committees
- 2. HHT-Animal Care Committee
- 3. ACC Documents
- 4. Scientific Merit Review
- 5. Ethics Review
- 6. AUP Submission
- 7. AUP Review Process
- 7.1. Instructions to Members
- 7.2. AUP Approval Process
- 7.3. AUP Archiving
- 7.4. External Studies/Collaborations
- 7.5. Guideline for the contracting-out of antibody production
- 7.6. Appeal Mechanism
- 7.7. Expedited Review
- 7.8. Pilot Studies
- 7.9. Umbrella AUPs
- 7.10. Guidelines for the use of biological material in animals
- 8. AUP Amendments and Annual Renewals
- 9. Animal Ordering and Maintenance
- 10. Secondary Use of Animals/Tissues
- 11. Investigator Training Programs
- 12. Post Approval Monitoring (PAM) Programs
- 13. Animal Housing & Use
- Appendix A: Examples of changes to an AUP that may be considered as Major Amendments
1. NRC Animal Care Committees
1.1. Terms of Reference:
The Terms of Reference for NRC Animal Care Committees (ACC) can be found on the NRC website.
2. HHT - Animal Care Committee
The ACC will be modified according to the needs of the Program and currently will be comprised of the following persons or representatives:
- 2.1.1. ACC Chairperson
- 2.1.2. ACC Coordinator - ex-officio (non-voting)
- 2.1.3. Community Member, at least one, although preferably two
- 2.1.4. Supervisor, Animal Resources Group (ARG) - ex officio
- 2.1.5. Health & Safety Representative (non-voting)
- 2.1.6. Veterinarian, experienced in laboratory animal medicine (ex officio, voting)
- 2.1.7 NRC employee who does not use animals for research
- 2.1.8. Researcher Representatives - At least one researcher experienced in animal use for each directorate that uses the animal facility.
- 2.1.9. Technical Officers Group or Research Associates Group, actively involved in animal care and/or use, at least one representative
2.2. Appointment of ACC Members:
The Director General (DG) of the Human Health Therapeutics Research Centre (HHT) nominates new ACC members and at the DG's discretion their terms may be extended.
2.3. Appointment of ACC Chairperson & Vice Chair:
The DG appoints the ACC Chairperson and Vice Chair and at the DG's discretion their terms may be extended. Note the Vice Chair will be appointed from the existing membership of the ACC.
Members will be nominated for a period of four years, normally renewed no more than once.
2.5. Meeting Frequency:
The ACC will normally meet on the third Thursday of each month, with the exception of the summer period, when meetings may be suspended due to the summer holiday season.
Quorum will be set at a simple majority of the full members that must include community and veterinary representation.
2.7. Committee Decisions:
The ACC will strive to obtain consensus on all ACC decisions. If a consensus cannot be reached a 2/3rds majority of those present will be accepted. Note that the Chairperson will normally refrain from voting. The minority opinion will be noted in the minutes.
When a member of the committee is absent for two consecutive meetings then the Chairperson contacts the person in order to discuss their continuing participation on the committee. The Chairperson then reports back to the committee to inform them of the results of the conversation.
3. ACC Documents
All ACC documents are considered confidential. External members and NRC employees sign a confidentiality agreement and must treat ACC documents appropriately. Accordingly, documents that are discarded are shredded or, if this is not possible, returned to the ACC Coordinator, who ensures that shredding is carried out.
3.2. ACC Meeting Agendas & Minutes:
Agendas and minutes are posted and archived which are available to all members in a shared location. Approved meeting minutes are sent to the DG.
3.3. Animal Use Protocol (AUP) Form:
The current version of AUP form is available to all members and to all users.
3.4. Annual Renewal and Amendment Form:
The Annual Renewal/Amendment Form is available to all members and to all users. This form serves several purposes including applying for annual renewals, amendments, animal order changes and personnel changes.
3.5. Completed AUPs and Amendment Submissions:
Signed original AUPs and amendments are archived in the office of the ACC Coordinator. ACC members are forwarded electronic copies. Electronic files are archived in the ACC-Email ACCount.
3.6. Standard Operating Procedures:
Standing Operating Procedures (SOPs) concerning ACC issues and the operation of the Animal Facility are posted in a location that is available to all users.
3.7. Emergency Response Document:
A document concerned with the handling of emergency situations involving animal use or the Animal Facility is posted in a location that is available to all users.
4. Scientific Merit Review
4.1. Scientific Review:
It is the responsibility of the HHT Research Centre management to ensure that all proposed activities that potentially include the use of animals meet the merit requirements as outlined in Scientific Merit Review form. Within the HHT Research Centre the Director of Operation is responsible for managing the merit review process.
4.2. Notification of merit:
The HHT Director of Operations notifies the ACC Coordinator when the scientific merit review process has been completed and if the proposed activity meets the merit requirements. The ACC can only finalize the approval of an application for animal use following written confirmation that the proposed activity has been found to have scientific merit.
5. Ethics Review
5.1. Ethics Review:
It is the responsibility of the ACC to ensure that all proposed activities described in Animal Use Protocols (AUPs) and associated amendments meets the standard of ethics as outlined in the CCAC Policy statement on: ethics of animal investigation.
6. AUP Submission
An electronic version of the AUP is sent to the /ACC Coordinator.
Completed AUPs ACCompanied by all additional documentation required are accepted for review during the next ACC meeting if submitted a minimum of five full working days prior to that meeting.
6.3. AUP Distribution:
ACC members are made aware of the submission via an email message indicating that an electronic file has been posted in the shared location. Note that the shared location is restricted ACCess to ACC members only.
7. AUP Review Process
7.1. Instructions to Members
7.1.1. When posting a reply in the shared location each member declares in the subject line one of three positions 1) No concerns 2) Concerns, or 3) Abstain. In the last two instances an explanation for abstaining and/or the concerns that need to be addressed are detailed.
7.1.2. ACC members are given (5) days to review an AUP.
7.1.3. If a member fails to post their position and any comments then the ACC Coordinator contacts them to remind the person of this responsibility.
7.1.4. When an AUP involves an ACC member as the principal investigator (PI) or the associated project leader, the other members submit their stance and comments to the ACC Coordinator. At the end of the review period, the ACC Coordinator collates the members' concerns and sends them out in an email to the PI for their response. In situations where comments are of questionable relevance, are contentious, or perhaps conflicting, then the Coordinator consults with the Chair to determine the best way to proceed. Ultimately a copy of the memo to the PI would also be posted in the shared location.
7.1.5. When the ACC Coordinator receives the PI's responses to ACC concerns, this information is communicated to the entire committee via a posting in the shared location.
7.2. AUP Approval Process
7.2.1. All AUPs are discussed at a monthly meeting before approval is granted. No animal orders are placed until approval is obtained.
7.2.2 If an ACC member is the PI or the associated project leader of an AUP to be discussed, the member is asked to leave the room during the discussion of that AUP.
7.3. AUP Archiving:
Hard copies of original AUPs and other related documents, i.e. renewal and amendment requests, are archived in the office of the ACC Coordinator. Electronic documents are archived in the shared location.
7.4. External Studies/Collaborations:
7.4.1. External Collaborations:
Animal use that is to take place off-site under the umbrella of a collaborative agreement, which may or may not involve NRC researchers working hands-on with the animals, must be carried out in an animal facility that is accredited by the CCAC (Canadian Council on Animal Care) or by AAALAC (Association for the Assessment and Accreditation of Laboratory Animal Care - International) or by an equivalent organization.
7.4.2. Contractual agreements:
Animal derived material (samples) provided by clients for analysis within NRC analytical facilities must have been obtained within animal facilities that are ACCredited by the CCAC (Canadian Council on Animal Care) or by AAALAC (Association for the Assessment and ACCreditation of Laboratory Animal Care - International) or by an equivalent organization. A copy of the documentation provided by the client identifying the animal species from which the samples were derived along with the identification of the ACCredited animal facility in which they were obtained must be forwarded to the HHT-ACC.
7.5. Guideline for the contracting-out of antibody production:
For antibodies to be produced specifically for the NRC by means of a contract, preference is given to suppliers that are CCAC or AAALAC accredited. However, if the contract organization is not CCAC or AAALAC accredited, then the ACC requires additional documentation that demonstrates the supplier meets an acceptable standard of animal care and maintenance.
7.6. Appeal Mechanism:
PI's seeking to appeal an ACC decision must bring this to the attention, in writing, of the DG. The DG in turn strikes an appropriate committee to review the ACC decision and the PI's concerns. The committee makes recommendations are made to the DG. The DG conveys these recommendations to the ACC and asks that they review their initial decision.
7.7. Expedited Review:
Normally all new AUPs are reviewed and approved only after a face-to-face meeting. However, in exceptional circumstances, where sufficient justification is provided, the following mechanism is in place to allow for an expedited review and approval. First, the Chairperson in consultation with the veterinarian determines if in their opinion there are justifiable grounds to initiate an expedited review. Assuming that there are grounds to hasten the review process, the ACC Chairperson, organizes an ACC meeting at the earliest convenience of the majority of the members, given that quorum would require the presence of a community member and the HHT Veterinarian. If a meeting cannot be reasonably arranged in time to meet the exceptional needs of the PI then the members are instructed, via email, to review the application and respond by email and/or the ACC Microsoft Folders with their approval or their concerns. Only after all concerns raised have been satisfactorily addressed and a 2/3rds majority of members, including a community member and the veterinarian, have given their approval is the application granted provisional approval. If a sufficient number of members did not respond then the Chairperson would attempt to contact individual members by phone. Following this provisional approval a meeting is called in a timely fashion in order to ratify the decision. If at that time additional concerns were identified then the committee would be free to request further information and/or rescind the provisional approval and stop any work in progress.
7.8. Pilot Studies:
The use of pilot studies prior to the commencement of larger studies is encouraged. Pilot studies still require evidence of scientific merit review.
7.9. Umbrella AUPs:
7.9.1. The ACC approves Umbrella AUPs when they meet the following criteria:
- 126.96.36.199. they are intended for repetitive studies with minor differences, such as multiple compound testing, antibody production; and
- 188.8.131.52. they are completed with the same level of detail as regular protocols.
7.9.2. Umbrella AUPs are identified as such by the use of the term "Umbrella" within the title. In addition, Umbrella AUPs only include a request for animals that are required to establish the standard procedure within the facility - the AUP should contain no request for additional animals. Once the procedure is established animal requests for specific studies are made through the use of a 'Service Request Form'. The Service Request Form is submitted to the ACC Coordinator and requires the approval of the ACC Chair and the Veterinarian only (if the Service Request Form contains significant deviations from the original procedure it may be forwarded to the full ACC for review).
7.9.3. Umbrella AUPs are exempt from Scientific Merit Review only in situations in which they support projects that have undergone successful Scientific Merit Review.
7.10. Guidelines for Use of Biological Materials in Animals:
7.10.1. Pathogens (see SOP):
Biological materials including cell lines, tumors, tissues, stem cells, and serum components of cell culture media can harbor murine pathogens capable of introducing disease into rodent colonies. Rodent colonies are screened for infectious diseases and are generally free of viruses and other microbial agents capable of interfering with the research. The health of the colonies and the integrity of research can be endangered by inadvertent introduction of untested biologicals carrying pathogens. All biological materials of unknown status of both rodent and human origin are therefore to be tested prior to inoculation into rodents.
7.10.2. Endotoxins (see SOP):
Antibody and other protein preparations that are used in animal studies for therapeutic purposes must be tested for bacterial endotoxins by an in vitro Limulus Amebocyte Lysate (LAL) test.
8. AUP Amendments and Annual Renewals
8.1. Request Coordination:
All requests are submitted to the ACC Coordinator using the Amendment/ Renewal form. The decisions related to requests that are reviewed by an individual or subcommittee are shared with the full committee at the next scheduled meeting.
8.2. Animal Order Changes:
Changes to the animal orders, not including requests to increase the number of animals used, but items like sex, strain, size, or weight, are reviewed by the Head, ARG.
8.3. Personnel Changes:
Personnel changes are reviewed by the ACC Coordinator, ARG Head, and/or HHT Veterinarian if the new person is working directly with animals they need to demonstrate that they have the appropriate training; otherwise training is arranged.
8.4. Minor Amendment:
A minor amendment is normally considered to be a request for additional animals less than 20% of the number approved in the initial AUP or a minor change in the procedures such as inclusion and/or modification of a level B category of invasiveness procedure. Minor amendments require both Chairperson and Veterinarian approval.
8.5. Major Amendment:
Major amendment requests must contain full details of the changes along with attached documentation as necessary. A major amendment is normally considered to be a request for additional animals in excess of 20% of the number approved in the initial AUP or a significant change to the original AUP. It should be noted that service requests for Umbrella AUPs are not considered a protocol amendment, and do not require the submission of an amendment form. Examples of proposed changes to an AUP that may be considered as major amendments are given in Appendix A. A major amendment requires full ACC review and approval. Whenever possible, the approval of Major Amendment takes place during a regular face-to-face meeting of the ACC. If this is not practical, Major Amendments can be reviewed and approved online. Online approval requires that a 2/3rds majority of members, including a community member and the veterinarian, have reviewed the amendment and given their approval.
8.6. New AUP Submission:
Significant changes to an AUP, beyond what is considered a major or minor amendment, require the submission of a new AUP and full ACC review. Examples of a major amendment include the following; a significant change in the direction of the research, the addition of completely different animal manipulations, the use of more invasive and more frequent procedures, the addition of new animal models, the addition of new research sites, etc.
8.7 Review of amendment classification:
Notwithstanding the definitions above, an ACC sub-committee comprised of the veterinarian and Chairperson may, based on the details of the request, deem any requested minor amendments to be major and any major amendment to require the submission of a new protocol.
8.8. Annual Renewals:
8.8.1. AUPs can be renewed up to three times. These requests must be submitted and approved prior to the end of the first, second, and third year in order to continue having animals on-site and/or to be able to order more animals. If there have been no major changes or problems related to the AUP then the request is granted approval by a subcommittee composed of the ACC Chairperson, the HHT Veterinarian and one community member, otherwise the request would require full committee review.
8.8.2. Annual renewals can be submitted as early as two months before the anniversary of the initial approval date.
8.8.3. Annual renewals must be submitted no later than ten working days before the first, second, and third anniversary of the initial approval date if there are animals remaining on-site; failure to do so requires the situation be brought to the attention of the full ACC committee and to be dealt with on a case-by-case basis.
8.8.4. In situations where no animals are present on-site, renewals are considered for a period of up to two months beyond the annual renewal expiry date. If a PI wishes to continue their studies after the two month grace period has passed, then a full AUP submission is required.
8.8.5. The ACC Coordinator sends a reminder notice two months in advance of the expiry date.
8.9. AUP Termination:
After a maximum of four years, all animal work must be again fully reviewed if the work is to continue.
8.9.1. An End of Study report is required upon AUP termination, either after the maximum AUP time limit has been reached or pre-term discontinuation of the AUP. The End of Study report is completed using the Annual Renewal and Amendment Form with its submission to the ACC Coordinator.
8.9.2. The End of Study report is reviewed by the Chairperson and HHT Veterinarian and is not subject to approval. The End of Study report is shared with the HHT-ACC for information / discussion purposes.
8.9.3. New AUP applications from a PI cannot be reviewed by the HHT-ACC until all of their pending End of Study reports are completed and submitted to the ACC Coordinator.
9. Animal Ordering and Maintenance
9.1. ACC-Approved AUPs:
Animals are ordered only after the AUP has received approval from the ACC.
9.2. Centralized Ordering:
All orders are placed via the Head of the Animal Resources Group or his/her delegate.
9.3. Cessation of Ordering:
Animals are not ordered if they cannot be guaranteed to arrive prior to the expiry date of the AUP.
9.4. Animal Transfer:
Animals on-site that are no longer required for a specific AUP may be transferred to an alternative AUP and be counted towards the approved animal requirement of that AUP. However, the ARG Head must be notified of the transfer in writing.
10. Secondary Use of Animals/Tissues:
It is permissible for other PIs to use the surplus tissues of animals euthanized on another investigator's approved AUP. However, this source of biological material is normally reserved for special occasions such as trying to refine a new test procedure and should not be considered a replacement for writing a category B AUP. In addition, the request must be made in writing to the Chairperson and the approved request attached to the AUP from which the animals will be used.
11. Investigator Training Programs
11.1. Animal Facility Orientation:
Prior to working with any animals all persons new to the HHT are required to undergo a short orientation program. The contents of the program are detailed in an Animal Resources SOP (AR-01-001).
11.2. National Institutional Animal User Training (NIAUT):
All persons involved with animal research are required to participate in a comprehensive web-based training program developed by the Canadian Council on Animal Care (CCAC). Only if new or completely revised relevant modules are produced would users be required to participate in additional training in the future (the requirement for automatic retraining has been dropped). The training is coordinated by the ACC Coordinator.
11.3. Clinical Competency:
Persons directly working with the animals are required to demonstrate that they have the required clinical skills. If they are lacking any skills then they are enrolled in one of the Animal Resources' training sessions or alternatively they are to make other efforts to obtain this training.
12. Post Approval Monitoring (PAM) Programs
12.1. Clinical Monitoring Forms:
Research involving procedures where animals might be expected to experience pain and distress have appropriate humane endpoints captured in the ACC-approved AUP. Observations are captured in room-level monitoring forms.
12.2. PI Submission of Endpoint Data:
PIs of D and E level AUPs submit to the ACC, every two months, the following data; the number of animals on each AUP that were euthanized according to experimental endpoints, the number of animals euthanized due to meeting humane endpoints, and the number of animals found dead. These numbers are reviewed by the ACC and action taken when appropriate.
12.3. AUP Audits and Procedural Reviews:
At least once during the course of a four-year AUP, and normally during the early stages of the work, an audit of the AUP is undertaken by a delegate of the ACC. This review normally involves arranging a time with the PI when animal procedures can be observed. A report on the audit is made available to the ACC.
12.4. Breeding Colony Report Review:
Monthly reports are prepared by Head of the Animal Resources Group or his/her delegate and are submitted to the ACC coordinator. These reports track the total number of animals bred, the number of those animals used on study and the number of animals culled. Reports are made available to the ACC for review and are stored in a shared location.
13. Animal Housing & Use:
13.1 Housing of Multiple Species:
There is no housing of multiple species within the same room or cubicle unless each species is housed in a rack of individually ventilated cages (IVC) and the various species are not in visual contact with each other.
13.2 Acclimation Period:
Normally testing procedures do not commence until the animals have acclimated for a period of no less than five days. Exceptions to this policy may be submitted to the ACC and are approved on a case-by-case basis.
Examples of changes to an AUP that may be considered as Major Amendments
- Addition of animal species.
- Addition of strains that are known to have specific housing/care requirements or health problems.
- Change in procedure(s) and/or new procedure(s) that have potential for increased pain or distress or change in humane endpoints.
- Increase in the category of invasiveness.
- Change from non-surgery to surgery, from minor to major surgery, from non-survival to survival surgery, or from single to multiple survival surgery.
- Modified choice of anesthetic or analgesic agent(s), or in the route of administration or dosage of these agents.
- Altered method of euthanasia.
- Change in duration, frequency or number of procedures performed on an animal.
- Increased discomfort to animal / addition of painful procedures (change in pain category).
- Withholding of analgesics.
- Unanticipated marked increase in clinical morbidity signs or proportion of animal deaths requiring increased numbers of animals.
- Change in Principle Investigator or person designated by Principle Investigator to be responsible for the AUP.