Animals in Research: Tips
to Keep Out of the
Doghouse
Brent C. Morse, DVM, DACLAM / Jacquelyn T. Tubbs, DVM, DACLAM
Division of Compliance Oversight
Office of Laboratory Animal Welfare
National Institutes of Health
Photo courtesy of Dr. Cathy Schuppli, DVM,
MSc, PhD, University of British Columbia
Institution
• Reporting is required by PHS Policy IV.F.3.
o Any serious or continuing
al noncompliance with PHS Policy
o Any serious deviation from the
Reporting: provisions of the Guide for the Care
and Use of Laboratory Animals
o Any suspension of an activity by the
IACUC
REPORTING IS A COOPERATIVE
PROCESS
OLAW will provide assistance and guidance.
Institution must demonstrate that corrective
actions are being implemented.
OLAW will evaluate appropriateness of the
actions in correcting and preventing the
reportable issue.
Self-reporting is part of enforced self-regulation.
TYPES OF REPORTABLE
INCIDENTS IN 2020
Physical Other Animal
Plant Issues Study
4% 14% Issues
No viola- 29%
tions
Identified
4%
IACUC-
Specific
Issues
4% Failure
Clinical to Follow
Issues Institu-
15% Animal Husbandry tional
11% Policies
19%
TYPES OF ANIMALS INVOLVED
Fish Not Specified by
5% All Other Species Institution
Car-
4%
ni- Ungu- 1%
voreslates NHPs
2% 3% 7%
Rodents
78%
INDIVIDUAL RESPONSIBLE FOR
REPORTABLE ISSUES:
Investigator &
71%
Research Team
Animal Care
12%
Staff
None 9%
IACUC 3%
Institution
1%
Other 2%
Vet Staff 2%
0% 10% 20% 30% 40% 50% 60% 70% 80%
INSTITUTIONAL CORRECTIVE
ACTIONS:
• Retrain personnel
• Counsel, reprimand, terminate
employment
• Modify institutional policies
• Repair or modify facility
• Enhance PI and study oversight,
probation
• Modify, suspend, or terminate
animal study protocol
IMPLICATIONS OF REPORTABLE
ISSUES:
• Corrective actions and improved systems with
better research outcomes
• Special terms and conditions of awards
• Enhanced reporting requirements
• Cost disallowance. Unable to publish data or use it
for grant proposals
• Suspension or termination of award (possible
repayment of funds)
• Damage to reputation, assessment of
peers/collaborators
• Retract or withdraw scientific publication
• Corrigendum or Errata to published article
COMMON FINDINGS SEEN WITH
NONCOMPLIANCE:
• LAB MEMBERS LACKING FAMILIARITY WITH THE PROTOCOL.
• INADEQUATE TRAINING OF INDIVIDUALS ON THE PROTOCOL.
• USE OF EXPIRED DRUGS.
• THE CONDUCT OF UNAPPROVED ACTIVITIES ON A PROTOCOL.
• RODENT CAGES WITHOUT FOOD OR WATER.
• INADEQUATE MONITORING OF ANIMALS.
HOT ISSUES IN COMPLIANCE OVERSIGHT
• POST-PROCEDURAL ANALGESIA – REMOVAL OF AMBIGUOUS LANGUAGE FROM PROTOCOLS
AND/OR SOPS REGARDING “PROFESSIONAL JUDGMENT” OR “WHEN REQUIRED” AND ASSISTING
THE RESEARCH TEAM BY ALLOWING THEM TO CREATE RECORDS OR CHARTS TO DOCUMENT
ADMINISTRATION.
• FAILED CO2 EUTHANASIA – INSUFFICIENT EXPOSURE TIME; LACK OF APPROPRIATE POST-
EXPOSURE OBSERVATION; NO SECONDARY PHYSICAL MEANS. NO FLOW METER OR PROPER
INSTRUCTIONS FOR USE OF CHAMBER(S). WELFARE ISSUE IF ANIMALS ARE FOUND TO HAVE
SURVIVED CO2 AND AWOKE IN FREEZER/REFRIGERATOR. SOME INSTITUTIONS ARE MORE
CLOSELY MONITORING CO2 EUTHANASIA AREAS AND/OR CARCASS DISPOSAL FREEZERS (TO
MITIGATE NEGATIVE IMPACT ON THE SURVIVING ANIMAL).
• FISH – PHYSICAL PLANT OR HUSBANDRY FAILURES OFTEN LEAD TO CATASTROPHIC LOSSES. MANY
FISH SPECIES ARE EXQUISITELY SENSITIVE TO MULTIPLE ENVIRONMENTAL PARAMETERS
(TEMPERATURE, SALINITY, PH, NITRATES, CHLORINE, OXYGEN, WATER FLOW, OZONE).
MORE HOT ISSUES IN COMPLIANCE OVERSIGHT
• LACK OF FOOD AND/OR WATER– COMBINATION OF ISSUES RESULT IN
DRINKING WATER NOT BEING AVAILABLE TO RODENTS. (WRONG CAGES
WITHOUT LIXITS, RECOIL HOSE NOT CONNECTED TO RACK, CAGES NOT
PROPERLY DOCKED, BOTTLES NOT PLACED PROPERLY, MICE TOO SMALL TO
REACH NIPPLE, RESPONSIBILITY FOR FEEDING NOT CLEAR, NEW CAGES NOT
SUPPLIED WITH FEED OR WATER, ETC.).
• ATMOSPHERIC/TESTING CHAMBER FAILURE – LACK OF CHAMBER
(HYPOXIA, SMOKE INHALATION, UV EXPOSURE, BEHAVIORAL ACTIVITY)
MONITORING AND/OR LACK OF ALARM SYSTEMS HAVE CONTRIBUTED TO
ANIMAL DEATH FROM MECHANICAL FAILURE.
QUESTIONS???
Real-Life Scenarios
Photo - courtesy of Dr. Cathy Schuppli, DVM, MSc,
PhD, University of British Columbia
CASE SCENARIO 1
• INVESTIGATOR AARON RODGERS (AT GREEN BAY UNIVERSITY) CONDUCTED A PROTOCOL
APPROVED SURGERY ON MICE AND THE ANIMALS RECOVERED SUCCESSFULLY. DURING
VETERINARY ROUNDS, THE SURGERY CARDS ON THE CAGES INDICATED THE ANIMALS WERE
ADMINISTERED AN OPIOID (BUPRENORPHINE SR) AND THE MICE EXHIBITED NO SIGNS OF PAIN
OR DISTRESS. HOWEVER, THE PROTOCOL STATES AN OPIOID AND NSAID (MELOXICAM) WILL
BE ADMINISTERED AS THE ANALGESIC REGIMEN.
• IS THE ADMINISTRATION OF 1 OF 2 APPROVED ANALGESICS CONSIDERED A NONCOMPLIANCE?
• YES
• NO
• UNSURE
HOW CAN CASE SCENARIO 1 BE AVOIDED?
• ENSURE ALL LAB MEMBERS ARE FAMILIAR WITH THE PROTOCOL (ESPECIALLY
IF AMENDMENTS WERE RECENTLY APPROVED AND ADDED TO THE
PROTOCOL).
• ASSIGN ROLES AND DESIGNATE WHICH INDIVIDUALS WILL PERFORM POST-OP
CARE AND ADMINISTER DRUGS. WILL IT BE THE SURGEON, LAB MANAGER,
OR PERSON PERFORMING EVENING CHECKS?
• UTILIZE A POST-SURGERY FORM OR CHECKLIST TO ENSURE ITEMS HAVE
BEEN COMPLETED.
CASE SCENARIO 2
• DURING MORNING HUSBANDRY CHECKS, A CAGE OF MICE WAS DISCOVERED LACKING AN
APPROPRIATE AMOUNT OF SPECIAL DIET. THE MICE WERE FOUND IN POOR CONDITION
BUT RECOVERED WITH SUPPORTIVE CARE. DISCUSSIONS WITH THE RODGERS LAB
REVEALED THE LAB WAS RESPONSIBLE FOR PROVIDING THE SPECIAL DIET AND THE MICE
HAD NOT BEEN MONITORED AS FREQUENTLY AS DESCRIBED IN THE PROTOCOL.
• WOULD YOU CONSIDER THE DECREASED FREQUENCY OF MONITORING TO BE A
NONCOMPLIANCE?
• YES
• NO
• UNSURE
HOW CAN CASE SCENARIO 2 BE AVOIDED?
• CREATE WEEKDAY AND WEEKEND FEEDING SCHEDULE AMONG LAB
MEMBERS.
• DOCUMENT WHEN FEEDINGS OCCUR (RECOMMEND KEEPING THE FORM IN
THE HUSBANDRY ROOM IF POSSIBLE).
• COMMUNICATE WITH THE HUSBANDRY TEAM THAT SERVICES THE ANIMAL
ROOM. PROVIDE CONTACT NUMBERS SO LAB MEMBERS CAN BE REACHED
READILY.
• REVIEW THE PROTOCOL WITH ALL LAB MEMBERS, EMPHASIZING THE
IMPORTANCE OF ADHERING TO THE MONITORING PLAN AND LAB’S
RESPONSIBILITIES.
CASE SCENARIO 3
• A LAB MEMBER PERFORMED CO2 EUTHANASIA INVOLVING A CAGE OF MICE. THE
INDIVIDUAL DID NOT PERFORM A SECONDARY METHOD OF EUTHANASIA (AS
REQUIRED BY THE EUTHANASIA SOP REFERENCED IN THE PROTOCOL). MICE THAT
RECOVERED FROM THE INCOMPLETE EUTHANASIA WERE FOUND ALIVE IN THE
CARCASS REFRIGERATOR LATER THAT DAY.
• WOULD YOU CONSIDER THE LACK OF CONDUCTING A SECONDARY METHOD OF
EUTHANASIA TO BE A NONCOMPLIANCE?
• YES
• NO
• UNSURE
HOW CAN CASE SCENARIO 3 BE AVOIDED?
• DETERMINE IF TRAINING IS APPROPRIATE (REVIEW LAB SOP, PROTOCOL TRAINING).
• DETERMINE IF POLICIES ARE CLEAR AND WELL DISSEMINATED (NOTICES VIA EMAIL,
POSTING OF APPROPRIATE SIGNAGE).
• REGARDING EUTHANASIA EQUIPMENT, ONE MUST ASK: IS THE EQUIPMENT CONSIDERED
EASY TO USE? IS AN AUTOMATED EUTHANASIA STATION AVAILABLE FOR USE?
• REGARDING LOCATION, IS EUTHANASIA ONLY OCCURRING IN A CENTRAL LOCATION
AND/OR BY “ANIMAL RESOURCES” PERSONNEL?
• USE OF A SECURITY CAMERA/CARD READER AT EUTHANASIA STATIONS MAY BE
BENEFICIAL.
CASE SCENARIO 4 (OH, NO LITTLE BUDDY!)
• DOCTOR GILLIGAN IS AN NSF-FUNDED RESEARCHER AT UNCHARTED DESERT ISLE
UNIVERSITY. SHE USES SEA BASS IN RESEARCH AND SOME TANKS AT THE UNIVERSITY
AQUATIC CENTER CONTAIN HER NSF-FUNDED FISH AND SOME CONTAIN BASS ON HER PROJECTS
FUNDED BY THE STATE DEPARTMENT OF AGRICULTURE. RECENTLY, SEVERAL TANKS OF STATE-
FUNDED FISH DIED WHEN THE BIOFILTERS FAILED DUE TO LACK OF MAINTENANCE. 600 FISH
WERE LOST OVER A 4-MONTH PERIOD. NONE OF DOCTOR GILLIGAN’S NSF-FUNDED FISH WERE
AFFECTED.
• IS THE LOSS OF THE 600 FISH REPORTABLE?
• YES
• NO
• UNSURE
