Transcript IACUC Updates: Discuss regulatory updates, new policies, and

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October 3, 2013
Christina Nascimento, MS, CPIA
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New IACUC Policies
o Disaster Planning
o Occupational Health
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Regulatory Updates
o The AVMA Guidelines for the Euthanasia of Animals: 2013 Edition
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Protocol Writing & Review
o Animal Usage, Justification for Use of Animals, & Breeding Colony
numbers
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Administrative Updates
Other Questions?
Topics for future sessions?
Laboratory-Level Emergency Response Resource Guide : Approved May 2013
Applies to: All users of research animals in laboratories.
Pre-Emergency Planning Steps:
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Know your building, department and local emergency plans.
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Register for Harvard’s Message Me notification
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Take weather forecasts into account when planning experiments.
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Maintain sufficient quantities of euthanasia agent(s) to euthanize all animals in the lab.
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Maintain paper copies of emergency contact lists and call trees in both home and work
areas..
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Verify that critical animal-related equipment is plugged into functioning emergency
outlets, if needed.
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Cryopreserve mouse strains (embryos or sperm) that are irreplaceable,
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If you have specific animals which cannot be replaced, contact facility supervisor to
identify them.
Emergency Action Steps:
 Obey all alarms and emergency notifications. Human safety is the top
priority.
 Evacuate first, then return animals to animal housing facility if possible
 If animals cannot be returned, secure the animals in cages and leave
immediately.
 Euthanize animals that are in imminent danger
 As soon as building re-entry is authorized, assess health and safety status
of the animals and make efforts to optimize their care
 Return animals to their designated housing facility, if possible; if not
possible, maintain contact with the animal facility manager/supervisor
and:
 Check animals more frequently in affected areas and report status
changes to animal facility supervisors or veterinary staff. Monitor
temperature and humidity.
 Animals that are found to be affected by extreme heat/cold/other
environmental conditions as a result of the emergency should be removed
from the environment and treated or euthanized
 Call the Facilities Emergency Number if animal lives may be at risk from a
facilities-related emergency.
Document training on Disaster Plan
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Requirements
o All personnel who work in laboratory animal facilities or have
frequent contact with animal must enroll in the occupational health
and safety program
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Procedure
o Initial questionnaire
o Follow-up
o Clearance
o Annual updates
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Changes
o Clearance required for inclusion on animal protocols
o No changes for BWH personnel
o Will be included in annual renewals
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HMS Only
o Surveys distributed and returned to OEHN
o Contact person at HMS to answer questions
Initial Health Questionnaire
Annual Update Questionnaire
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Relevant changes:
o CO2 displacement rate for rodents
o Cervical dislocation for rodents
o Chilling of zebrafish
o OLAW Webinar: http://www.youtube.com/watch?v=c8ivjAysVBI
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CO2: acceptable “with conditions”:
o CO2: Gradual displacement rate of 10-30%
o Flowmeters attach to CO2 source
o Suggest post SOP at euthanasia station
o
o
Dwyer instruments : VFA-24 (2" scale) or VFB-66 (4" scale)
Airgas: Western® CGA320 12 LPM Flowmeter Regulator WESM1-320-12FM
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Cervical Dislocation without anesthesia acceptable “with
conditions”
o Animal Protocol must be amended and approved by the IACUC before
performing cervical dislocation
• Scientific justification no longer needed
• Performing the euthanasia method without IACUC approval would be
considered “off protocol”
o Amendments approved with the method will be sent to the HCCM
Manager of Training.
o Lab must set up a training session with the HCCM Manger of Training
for cervical dislocation
o Training in the procedure must be documented in the lab’s animal
procedure training records.
o Only after all the steps above are completed, can the lab proceed with
performing the procedure
Species
# Used per year
CATEGORY B -Teaching, research, or tests that involve breeding or housing of animals only
Breeding colony
Housing ONLY (no other procedures)
Total number of animals to be used in Category B only
CATEGORY C -Teaching and/or research experiments that do not involve more than momentary
pain and/or distress or require the use of pain relieving drugs.
Alert animals (behavioral observation or brief restraint)
Anesthetize and release for non-invasive procedures (e.g. imaging, bandage change)
Change in environmental parameters (diet, light cycle, room temperature, etc.)
Chemical carcinogens (e.g. BrdU)
Euthanasia with or without tissue/organ harvest
Forced exercise
Gavage
Irradiation
Microbiological agents
Non-surgical collection of body fluids (blood, urine, etc.)
Radioisotopes
Simple injections (IP, IV, etc.)
Tail biopsy for genotyping (mice under 21 days)
Use as a parasitic host
Total number of animals to be used in Category C
Introduction of illness (including the administration of toxins, microbiological agents,
clinical transgenic phenotypes)
Lavage
Multiple MAJOR survival surgery
Multiple MINOR survival surgery
Non-survival surgery
Physical trauma
Survival surgery: MAJOR
Survival surgery: MINOR
Tail biopsy for genotyping (mice over 21 days)
Toxic substances (e.g. streptozotocin, MPTP, cisplatin, doxycycline)
Transgenic mouse production (embryo manipulations to produce novel strains, etc.
Tumor induction or implantation
Unusual or prolonged restraint (e.g. pie chamber, chair)
Use of paralytic agents
Total number of animals to be used in Category D
CATEGORY E – Teaching and/or research experiments, surgery or tests that involve PAIN and/or
DISTRESS, and for which appropriate anesthetic, analgesics or tranquilizing drugs are NOT used
because they would adversely affect the results or interpretation of data.
Death-as-an-endpoint* studies
Lethal dose studies*
Noxious stimuli from which there is no escape
Pain study
Withholding of post-operative analgesia for any surgical procedure
Total number of animals to be used in Category E
*You must follow the Guidelines for ‘Death as an Endpoint’ or ‘Lethal Dose’ studies at:
https://www.hms.harvard.edu/ORSP/Secure/animal_guidelines.html
Note: For all procedures in Categories D & E (below) a search must be completed in Section P
CATEGORY D – Teaching and/or research experiments or tests that will involve pain and/or
distress and for which appropriate anesthetic, analgesic or tranquilizing drugs will be used.
Anesthetize and release for non-surgical painful procedures (e.g. retro-orbital bleeds)
Antibody production: ascites
Antibody production: polyclonal (non-ascites, no footpad)
Burns
Controlled drugs or substances (as test material, e.g. cocaine)
Electric shock
Food or water deprivation other than pre-surgical fasting
Footpad injections (antibody production or microorganism)
Introduction of illness (including the administration of toxins, microbiological agents,
clinical transgenic phenotypes)
EXCEPTIONS to STANDARDS – Select any policy deviations that will be required in this protocol. Scientific
justification must be included in the indicated section of the protocol and/or separate exemption form.
Section D.4
Single housing of animals
Section D.4.c
Withholding of enrichment from singly housed animals
Section E & Exemption
Euthanasia methods that are not consistent with the AVMA Guidelines
Section G & Exemption
Ascites collection
Section I.7
Non-pharmaceutical grade drugs and other compound suspensions
Section J.2.k & Exemption
Withholding postoperative analgesia**
Section N
Food/water withholding or scheduling (not ad-lib)
Exemption form
Smaller caging than the recommended space allotment (e.g.: CLAMS)
Exemption form
Deviations from housing density standards
Exemption form
Toe-clipping for identification purposes
Section N
Deviations from the 12/12 hour light/dark cycle
Exemption form
Any other exceptions to the standards of the PHS Policy, the Guide, or the
AWA. - Please specify:
2.
JUSTIFICATION FOR THE USE OF ANIMALS
Federal Assurances: You are required by federal law to provide the following justifications.
Why are animals needed for this study? (i.e.: Could the same information be obtained by
experiments using tissue culture or computer models? If you are generating antibodies, could you use in vitro
methods?)
a.
b.
Justify choice of each species:
Justify the number of animals to be used: (You must convince the Committee that the number of
animals is appropriate to the work being proposed. Provide groups and statistical analysis to be used if relevant.)
c.
Discuss your strategy to reduce the number of animals and to minimize pain and distress
d.
to your animals: (examples include: earlier euthanasia, decreasing the number of time points, changing the
methods to those that are less invasive):
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A.2.c: Justify the number of animals to be used:
o
Example: We estimate we will need a maximum number of 3175 animals over the 3year approval period. This number is based on an estimated number of 60 novel
agents that will be screened for anti-inflammatory properties. This total number is
based on 60 studies/3 years with 50 animals/study; 6 groups per study (2 control
groups with 5 animals/group and 4 test groups with10 animals/group). Control group
1 will receive the inflammatory agent followed by treatment with vehicle only. Control
Group 2 will receive inflammatory agent followed a well-established anti-inflammatory
agent. Test groups will receive the inflammatory agent followed by treatment with a
potential therapeutic (novel) agent at 4 different concentrations, respectively. Since
we anticipate that as many as 5% of the animals will not exhibit a sufficient minimum
initial inflammatory response to be entered in the study, we are requesting an
additional 150 animals. In addition, we are asking for an additional 25 animals for
the purpose of training research staff in the proposed manipulations (e.g. foot pad
injections, iv administration of test compounds, measurements of inflammatory
response).
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Describe the logic behind the proposed number of animals per group:
o Example: We will be testing one novel agent at 4 different concentrations
per study (i.e. 4 test groups per study). The selected dose concentrations
will be based on what we estimate to be the smallest concentration
necessary to confirm anti-inflammatory properties, up to the highest
concentration necessary to maximize anti-inflammatory properties without
causing toxicity, and two additional intermediate doses to see if a maximum
anti-inflammatory threshold can be achieved at lower doses. We will also
treat one control group with vehicle only, and a second control with a wellestablished anti-inflammatory compound at its most efficacious dose. The
number of animals per group is based in a student’s t-test or a one-way
ANOVA. In addition, the necessary number of animals per test and control
groups in this screening approach is well established in the literature:
(reference relevant publications).
e.
Breeding Colony users only: The estimated numbers of animals in breeding colonies must be
provided and justified. These numbers must be also be tracked on a log sheet in the animal housing room.
i. Estimated number of breeding adults:
ii. Estimated number of offspring produced:
iii. Estimated total number of offspring euthanized without research use:
iv. Criteria for offspring euthanized without research use:
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Estimate number of breeding adults, offspring produced, and
number of offspring euthanized without research procedures
performed:
o Example: Assuming each breeder pair will produce an average of 1 litter of 5
pups per month and will breed for 3 months, 15 pairs should produce
15x5x3=225 mice in 3 months, i.e. 75 mice per month or 900 mice per year X
3 years of the approval period is 2700 mice that can be used in experiments or
to refresh the breeders. After this initial phase, 360 of the offspring will be used
to refresh breeders, leaving an estimated 2340 mice (1170 males, 1170
females) for experiments. However, since we are only interested in female mice
for our study; of the 2340 mice only 1170 will be used in experiments and the
other 1170 males will be euthanized without use. We also anticipate that
approximately 50 offspring will be produced at a time when we cannot use them
and therefore will be euthanized without use. We will try to keep the number of
animals produced in excess to a minimum by separating breeding pairs as
needed to reduce production.
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Section S and Annual Renewal:
o No signatures required by lab members other than PI
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Research Officers assigned to specific PIs
Rolling Protocol submissions
Questions?
Suggestions for future topics?