Purpose

In order to comply with government regulations and to make the modification approval process as simple as possible for the Principal Investigators (PI), the IACUC has established a policy on modification review and approval.

Action

Any change to a protocol requires the PI to submit a modified protocol through InfoEd.  This is sent to the IACUC office and the IACUC Administrator reviews the modification for processing.  The IACUC Administrator is responsible for determining if a modification is major (significant) or minor; however, the ultimate decision, should there be any questions, will lie with the IACUC Chair.

Table one below lists examples of modifications that would be considered minor or major (significant).  Table two below lists examples of modifications to be reviewed by various review methods.

IF THE MODIFICATION IS MINOR: Review of the submitted modification will be reviewed administratively for approval by an appropriate member of the IACUC.  If there are any questions regarding the assignment of an appropriate member, the IACUC Chair will review the modification.  No other review by the IACUC is required.

IF THE MODIFICATION IS MAJOR: The modification will be reviewed by the IACUC according to federally recognized review processes:  Full Committee Review (FCR), Designated Member Review (DMR), or Veterinary Verification and Consultation (VVC).  The IACUC Administrator is responsible for determining a review type; however, the ultimate decision, should there be any questions, will lie with the IACUC Chair.

Full Committee Review:  If the IACUC Administrator determines that the significant modification requires a full committee review, it will be processed as such.  The modification will be assigned appropriate reviewer(s) and will be reviewed by the full committee at a regularly convened meeting.

Designated Member Review:  If the IACUC Administrator determines that the significant modification meets the criteria for a DMR review, it will be processed as such:

1. Notification of the submission of the modification will be sent to the entire committee so that each member may make a determination of whether or not they wish to call for a full committee review of the modification.  The IACUC Administrator will generally allow a few days for this review; however, exceptional circumstances may warrant a shorter review time period.
2. The modification will remain on the agenda covering the request period for documentation purposes.
3. It is the responsibility of the IACUC member(s) assigned to review the modification to do so by the assigned due date.
4. The modification does not get reviewed at a regularly convened IACUC meeting.

Veterinary Verification and Consultation Review:  If the IACUC Administrator determines that the significant modification meets the criteria for a VVC review, it will be processed as such:

1. The modification request will be sent to the Attending Veterinarian (AV) for approval.  Certain circumstances may warrant that the request also be reviewed by safety personnel (if there is an addition of the use of a hazardous chemical or biological agent).
2. The modification will remain on the agenda covering the request period for documentation purposes.
3. It is the responsibility of the AV assigned to review the modification to do so by the assigned due date.
4. The modification does not get reviewed at a regularly convened IACUC meeting.

The initial determination of modification requests to be minor or major (significant) and the review type (FCR, DMR, or VVC) will be performed by the IACUC Administrator.  Should there be any questions regarding whether or not a modification is considered to be minor or major (significant), it will be decided by the IACUC Chair.  Should there be any questions on the assignment of a review process for major (significant) changes, it will be decided by the IACUC Chair.

TABLE ONE:  Examples of Major (Significant) vs. Minor Modifications

Major- Requires IACUC Review	Minor- Handled Administratively
Change in purpose or aim of a study	Addition of qualified personnel (other than PI)
Change in Principal Investigator	Addition or deletion of funding sources
100% or greater increase in rodent animal numbers	Addition or deletion of room locations
25% or greater increase in non-rodent animal numbers	<100% increase in rodent animal numbers
Addition of survival surgery	<25% increase in non-rodent animal numbers
Addition of painful procedure	Need to repeat an experiment
Housing of animals in a location that is not part of the animal program overseen by the IACUC	Addition of animal strains, including transgenic or gene targeted lines
Any changes that have the potential to impact personnel safety
Changes in experimental procedures
Addition of experimental procedures
Addition of species

TABLE TWO:  Major Modifications- Criteria for FCR/MDR/VVC Reviews

Full Committee (FCR)	Designated Member (DMR)	Veterinarian (VVC)
Addition of major survival surgery	Chage in purpose or specific aim of a study	Changes to anesthesia and analgesia
Addition of painful procedures	Change in Principal Investigator	Addition of non-invasive sample collections
Death as an Endpoint	Housing of animals in a location that is not part of the animal program overseen by the IACUC	Addition of experimental substances (note:  may require safety review)
Any exceptions to regulations or standards	Any changes that have the potential to impact personnel safety	Euthanasia to any AVMA-approved method
Addition of a new USDA-regulated species	Addition of new non-USDA-regulated species	Addition of sample collection times
	Addition of minor survival surgery	Addition of experimental procedures that will not result in pain/distress to the animals (e.g., pain category B or C procedures)

 

Effective Dates:  December 2, 2021 through December 30, 2024

 

Purpose

The Institutional Animal Care and Use Committee IACUC) recognizes that ensuring compliance with approved animal care and use protocols is an important aspect of a laboratory animal program. The purpose of a post approval monitoring (PAM) program is to work with investigators to facilitate their animal research and to be proactive in identifying potential problems in their compliance with active IACUC protocols. The PAM program at UConn Health will operate under the acronym PAWS: Post-Approval Animal Welfare Support.

Action

1. All PAM will be under the supervision of the IACUC and will be performed by a designated Compliance Liaison Officer (CLO) accompanied by one voting member of the animal Care Committee.  A minimum of 12 reviews will be performed per year.

2. All active animal care and use protocols are eligible for PAM review. Criteria which may increase the frequency of PAM protocol review include:

• Animal use in pain categories D or E
• Significant personnel changes
• Significant increases in protocol activity
• The use of biohazards and/or carcinogens
• The use of physical restraint
• The use of food and/or water restrictions

3. A summary of the findings of PAM reviews during a given month will be reported to the IACUC at its monthly meeting.

4. The PAM program consists of the following areas:

• Semi-annual inspections;
• Unannounced drug inspection visits;
• Observation of procedures:
• Records review;
• Housing room inspections;
• Review of new protocols with investigative staff prior to first use; and
• Any aditional activity deemed to be appropriate by the IACUC and/or IACUC staff.

5. The PI and the senior research staff for the reviewed protocol are required to be present during a PAM review to facilitate the review; this likely depends upon the activity being reviewed.

6. Issues that pose a significant threat to animal welfare will be referred immediately to the attending veterinarian for resolution and also to the IACUC for further investigation.

7. A written report of the monitoring results, including suggested corrective actions, will be brought to a meerting for review by the IACUC.

8. The PI will have 28 calendar days from the IACUC meeting date of the discussion of the initial PAM review to respond to any identified deficiencies and recommended corrective actions. Investigators who disagree with PAM review results, recommendations, or corrective actions can appeal their concerns to the IACUC.

9. The IACUC chair (or designee) will review and approve the PI’s responses. If the PI’s responses are not acceptable, the IACUC chair (or designee) will seek further revisions and the PI will have 14 additional days to respond.

10. If the PI does not respond to the inspection findings of the PAM activity conducted within the appropriate time frame as outlined above, the ACC will then decide on how to proceed.

Effective Dates:   June 6, 2024 thru June 30, 2027

 

Purpose

Many Tg/GT animals are being constructed that require monitoring by the IACUC to comply with various federal regulations. When reviewing protocols, the IACUC has the responsibility to ensure the necessity for the use of live vertebrate animals and to ensure the appropriate use of species and strains for the proposed work.

Action

1. Any Tg/GT animal to be constructed and/or used at UConn Health must be named and described in an approved animal care and use protocol. This includes animals destined for use at either the UCHC or an outside institution.

2. All Tg/GT will be assigned a Genetically Modified Organism (GMO) number by the BSO or IACUC coordinator.  This GMO number must be reflected on the cage cards housing Tg/GT animals.

3. It is the responsibility of the PI to inform the IACUC if there are any phenotpyic pain or distress associated with the line, including unexpected lethality.  If this is not known at the time of initial use, it must be reported to the IACUC immediately upon discovery.

4.  Protocols must clearly indicate the recombinant lines to be used in that protocol.

 

Effective Dates:  June 1, 2023 through June 30, 2026

This policy has been approved by a majority vote of the IACUC members.

Purpose

In order to ensure appropriate use of Tribromoethanol (Avertin), UConn Health’s Institutional Animal Care and Use Committee (IACUC) has implemented a policy on the use of this drug. The IACUC encourages the use of pharmaceutical grade compounds such as ketamine/xylazine and isoflurane rather than Tribromoethanol.

Background

Tribromoethanol (Avertin) is an anesthetic that provides rapid induction and recovery for single use, short duration (approximately 15-20 minutes) surgical procedures in rodents. Tribromoethanol has been commonly used in the production of transgenic animals to facilitate procedures such as embryo transfer, vasectomy, or distal tail snip for DNA analysis. Tribromoethanol is not commercially available and investigators who wish to use it as an anesthetic must make their own solutions. Improper preparation, storage, or use of Tribromoethanol can result in high mortality losses. In particular, Tribromoethanol degrades in the presence of heat and light, producing toxic by-products that are potent gastrointestinal irritants. Adverse effects are common in mice following any second exposure to Tribromoethanol regardless of the dosing interval; therefore, this anesthetic is approved for one administration only as a survival anesthetic in mice.

Any proposed deviation from these guidelines must be fully explained and justified to the IACUC in the research proposal.

Action

Preparation

Tribromoethanol must be prepared as follows:

• Dissolve 2.5 grams of 2,2,2-tribromoethanol in 5 ml of tert-amyl alcohol.  This requires heating to approximately 40°C and stirring vigorously.
• Add sterile PBS, stirring continuously, up to a final volume of 200 ml
• Filter sterilize through a 0.5 micron filter
• Aliquot the final solution into sterile light protected containers.  Containers must be labeled:
  • Tribromoethanol
  • 12.5 mg solution
  • Date of preparation
  • Date of expiration (two weeks from reconstitution)
  • Initials of person who prepared the solution

Storage

Tribromoethanol must be stored at 2-8°C in light protected containers.

Use

Tribromoethanol may be approved for use after scientific and/or medical justification has been provided has been provided in the animal care and use protocol and after IACUC review for a single, survival administration to adult mice. If a second administration of tribromoethanol is given, the animals must be euthanized prior to awakening from the anesthetic. The anesthetic should be administered at a dose of 250 mg/kg given IP.

Dispose of any solution that is past the two-week expiration date, has crystals, or has changed from a clear solution to a yellow solution.

References

1. Papaioannou, VE and Gox, JG. Efficacy of Tribromoethanol Anesthesia in Mice. Laboratory Animal Science, 1993. April, 43(2): 189-192.

2. Zeller, WM; Burki, G; and Panoussis, B. Adverse Effects of Tribromoethanol as Used in the Production of Transgenic Mice. Laboratory Animal Science, 1998. October, 32(4): 407-413.

3. Kohn, DF; Wixson, SK; White, WJ; and Benson, GJ. Anesthesia and Analgesia in Laboratory Animals, 1997.

4. Efficacy and Safety of Stored and Newly Prepared Tribromoethanol in ICR Mice. Contem Top Lab Animal Sci, 2005. 44(1): 17-22.

5. An Evaluation of Preparation Methods and Storage Conditions of Tribromoethanol. Contem Top Lab Animal Sci, 2005. 44(1): 11-16.

Effective Dates: June 6, 2024 thru June 30, 2027

Purpose

There are many circumstances that involve partnerships between collaborating institutions or relationships between institutional animal care programs. OLAW and USDA-APHIS agree that review of a research project or evaluation of a program or facility by more than one recognized IACUC is not a federal requirement.

It is imperative that institutions define their respective responsibilities. PHS Policy requires that all awardees and performance sites hold an approved Animal Welfare Assurance. OLAW negotiates Inter-institutional Agreement Assurances of Compliance when an awardee institution without an animal care and use program or IACUC will rely on the program of an Assured Institution. Assured institutions also have the option to amend their Assurance to cover non-assured performance sites, which effectively subjugates the performance site to the Assured institution and makes the Assured institution responsible for the performance site.

If both institutions have full PHS assurances, they may exercise discretion in determining which IACUC reviews research protocols and under which institutional program the research will be performed. It is recommended that if an IACUC defers protocol review to another IACUC, then documentation of the review should be maintained by both committees. Similarly, an IACUC would want to know about any significant questions or issues raised during a semi-annual program inspection by another IACUC of a facility housing a research activity for which that IACUC bears some responsibility or exposure. This policy defines when UConn Health will accept another institution’s IACUC approval and/or require submission to the UConn Health’s IACUC.

Action

1. Work performed at UConn Health with the funding administered through another institution:

• The UConn Health’s IACUC will review and approve all animal care and use activities performed at this institution. The work must have a UConn Health faculty member sponsor and the Principal Investigator must complete the UConn Health’s animal care and use protocol form. All personnel involved in the study performed at this institution must comply with all IACUC policies and procedures.

2. Work performed at another institution with the funding administered through UConn Health:

• UConn Health’s IACUC will accept the review and approval of the institution performing the work if the following are met:
  • UConn Health’s IACUC receives a copy of the protocol approval letter from the institution.
  • UConn Health’s IACUC receives a copy of the IACUC approved protocol from the institution.
  • UConn Health’s IACUC receives a copy of the latest semi-annual inspection report to the IO.
  • Additional documentation may be requested at the discretion of the IACUC chair.
• If any of the above requirements are not met, then the PI will be required to submit a protocol to the UConn Health’s IACUC for review.

3. Work performed at UConn Health and another institution with the funding administered through UConn Health:

• This will be handled for each institution as described in 1 and 2 above.

4. Work performed at UConn Health under an agreement which may be for pay or collaboration for an institution or company:

• If the institution or company has an IACUC, the UConn Health’s IACUC will accept the review and approval of the institution performing the work if the following are met:
  • UConn Health’s IACUC receives a copy of the protocol approval letter from the institution.
  • UConn Health’s IACUC receives a copy of the IACUC approved protocol from the institution.
• If the institution or company does not have an IACUC, the work will be performed as described in 1 above.

This policy  has been approved by a majority vote of the IACUC members

Effective Dates: June 6, 2024 thru June 30, 2027

Purpose

In order to comply with government regulations (PHS and USDA), the Association for the Assessment and Accreditation of Laboratory Animal Care International (AAALAC), and the Guide for the Care and Use of Laboratory Animals, the University of Connecticut’s Institutional Animal Care and Use Committee (IACUC) has implemented a policy regarding semi-annual program review and facility inspections.

Action

1. Animal study area is defined as “any building, room, area, enclosure, or other containment outside of a core facility of centrally designated or managed area in which animals are housed for more than 12 hours if it houses a USDA regulated species and more than 24 hours for other species.”

2. The Office of Laboratory Animal Welfare (OLAW), NIH, has issued a document which states “when considering IACUC responsibilities for semi-annual review, it is important to keep in mind that the institution, acting through the IACUC, is responsible for all animal-related activities of the institution, regardless of where animals are maintained or the duration of their stay.”

3. In May and November of any calendar year, the IACUC will conduct a facility inspection to include all CCM areas including, but not limited to: animal holding rooms (including any satellite facilities), animal study areas, cage wash areas, food and bedding storage areas, and any other area deemed appropriate. In addition, all laboratories in which animals are listed as being used will be inspected along with laboratories where animals are held for more than 12 (USDA-regulated species) or 24 hours (all other species).

4. Once the inspections are completed, the IACUC will hold a special meeting to review the animal care and use program and the results of the facility and laboratory inspections. A report will be generated by the IACUC coordinator which will be signed by a majority of a quorum of the IACUC and will include any minority views. This report will then be submitted to the institutional official.

Effective Dates:   December 1, 2022 through December 31, 2025

Purpose

Varieties of acceptable and recognized methods are available for individually identifying research animals. These include, but are not limited to, ear tags/notches, tattoos, sutured beads, subcutaneous transponders, colored stains, dyes, and freeze brands. The Guide for the Care and Use of Laboratory Animals states “As a method of identification of small rodents, toe-clipping should be used only when no other individual identification is feasible.  It may be the preferred method for neonatal mice up to 7 days of age as it appears to have few adverse effects on behavior and well being at this age, especially if toe clipping and genotyping can be combined.  Under all circumstances, aseptic practices should be followed.  Use of anesthesia or analgesia should be commensurate with the age of the animals.”

Toe clipping is the removal of the last phalangeal (toe) bone of a digit from one or more limbs. It is usually done for the purpose of identification and genotyping of animals. The Food and Drug Administration also discourages the use of toe clipping as a means of animal identification. The UCHC Institutional Animal Care and Use Committee (IACUC) typically does not approve the use of toe clipping when performed only for the purposes of identification.

The Interagency Research Animal Committee considers toe clipping to be a painful procedure; however, it may be done only after IACUC approval with proper justification:

a) Toe clipping is done for unique and highly individualized animal identification that is permanent and unambiguous and is used for the long-term identification of potential breeding mice;

b) If the neonates need to be identified before day 7, toe clip is preferred;

c) If the same animal must be genotyped, then the animal may only undergo one procedure for both tissue harvest or genotype and permanent identification;

d) When no other individual identification method is feasible (such as ear notching, ear tags, tatooing, or subcutaneous implantation of a transponder identification chip);

e) Toe clipping for the sole purpose of obtaining DNA is not acceptable; and

f) The toe clip procedure should be detailed in the IACUC protocol.

Action

1. Toe clipping can be performed on pups up to 12 days of age; the preferred age is less than 8 days of age.  Toes may be removed without anesthesia on mice up to 8 days of age.  Toes must be removed with anesthesia on mice 8 days of age or animals whose eyes have opened and appropriate post-operative analgesics must be used.

2. The procedure should be performed with sharp, disinfected scissors.  Scissors must be disinfected between animals.  Research presonnel should confirm that there is no bleeding prior to returning the animal to its cage.

3. Toe clipping is limited to no more than one per foot.

4. Since the rodents hold food with their forepaws, the IACUC will only allow this procedure on hind paws, one toe per paw, and permits the removal of just the first bone.

5. The procedure is not recommended for rodents used in psychology research as it may affect the gait or grip strength of the animal.

References

1. The Guide for the Care and Use of Laboratory Animals. National Research Council, National Academy Press, 2011.

2. IACUC Guidebook, 2nd Edition, NIH, Office of Laboratory Animal Welfare, 2002.

3. Good Laboratory Practice Regulations; Minor Amendment, Federal Register, VOl. 54, N. 75, 1989. (www.nal.usda.gov/awic/legislat/fdaclip.htm)

4. National Institutes of Health, ARAC, Guidelines for Toe Clipping of Rodents, Revised 5/12/04. (http://oacu.od.nih.gov/ARAC/).

Effective Dates: June 6, 2024 thru June 30, 2027

Purpose

The Guide for the Care and Use of Laboratory Animals states that newly received animals should be given a period for physiological, psychological, and nutritional stabilization before their use. This allows animals to recover from shipping stress and permits them to adapt to their new surroundings. The length of time for stabilization will depend on the type and duration of animal transportation, the species involved, and the intended use of the animals. This policy will guide the amount of time an animal should be allowed to acclimate to the facility after their arrival from another institution.

Action

Non-Terminal Procedures

1. Rodent species should have a minimum acclimation period of 72 hours.

2. Non-rodent species should have a minimum acclimation period of 7 days.

3. Aquatic species should have a minimum acclimation period of 72 hours.

Terminal Procedures

1. For rodent species, an acclimation period of 48 hours is recommended, but is optional.

2. For non-rodent species, an acclimation period of 72 hours is recommended, but is optional.

3. For aquatic species, an acclimation period of 48 hours is recommended, but is opotional.

Terminal Training Procedures

No acclimation period is required for any species.

The PI should take into consideration the stress-induced variable in the research outcomes. For requirements for other unidentified  species, please contact the Center for Comparative Medicine Attending Veterinarian.

Effective Dates:      December 7, 2023 through December 31, 2026

Purpose

In order to comply with government Regulations (USDA Animal Welfare Act and Animal Welfare Regulations), the UConn Health’s Institutional Animal Care and Use Committee (IACUC) has implemented a policy implementing a training form for individuals who are performing research, testing, or training on USDA-regulated species.

Action

1. All individuals who perform research, testing, or training on a USDA-regulated species are required to fill out, and maintain, an IACUC animal training records form.

2. This form is to be maintained by each individual using the regulated species.

3. Training forms must be attached to the protocol record if the protocol is an InfoEd Animal Use protocol submission.

Effective Dates: February 26, 2015 thru January 31, 2018

Purpose

In order to comply with Federal Regulations (USDA and PHS) and the Guide for the Care and Use of Laboratory Animals, the UConn Health’s Institutional Animal Care and Use Committee (IACUC) has established a policy on requirements for reporting unusual or unexpected morbidity and/or mortality in a research project.

Action

1. If, during the course of a research project, any unusual animal deaths or significant health related problems occur, the Principal Investigator must report the incident within 72 hours from time of discovery to the IACUC (via the IACUC Coordinator) and the Director of the Center for Comparative Medicine (CCM). The Attending Veterinarian should also report any incidences of unusual animal illnesses and deaths to the IACUC via the IACUC Coordinator when they are discovered during review of animal morbidity and mortality reports.  This includes the discovery of any unanticipated pain, distress, or lethality of transgenic/gene-targeted animal lines.
2. It is at the discretion of the Attending Veterinarian what action, immediate or otherwise, is needed to prevent, reduce, or minimize any further animal suffering. This may include removal of the animal(s) from the study and/or euthanasia of the remaining animal(s).
3. There should be a combined effort of the IACUC, the Attending Veterinarian, and the Principal Investigator to arrive at a workable plan to prevent further morbidity and mortality for the duration of the research project.

Effective Dates:   December 1, 2022 through December 31, 2025