Harvard Medical Area (HMA) Standing Committee on Animals – “Established in 1907”

Harvard Medical Area HMA Standing Committee on Animals – “Established in 1907” 180 Longwood Avenue, Suite 113 Boston, MA 02115 Tel: 617-432-3192 Fax: 617-432-3169 Contact Phone & Email

Harvard Medical Area (HMA) Standing Committee on Animals – “Established in 1907”

180 Longwood Avenue, Suite 113 Boston, MA 02115 Tel: 617-432-3192 Fax: 617-432-3169

Contact Phone & Email

BIDMC PI Check here: BIDMC investigators must send an approved copy of this protocol to BIDMC, East Campus, RN150D

Protocol Title

Funding Source

Grant Number & Title

Check one:

This proposal has been reviewed and approved by the HMA Standing Committee on Animals

Table of Contents

Sections listed in BOLD must be completed for every protocol

Sections F through N are to be completed only as they apply to your protocol.

HCCM’S MANDATORY RISK DISCLOSURE (MRD)

MRD: MANDATORY RISK DISCLOSURE - Hazardous substance disclosure sheet

STOP YOU MUST RECORD AND CHECK OFF THE FOLLOWING PERTAINING TO YOUR SUBMITTED PROTOCOL: FAILURE TO DO SO WILL RESULT IN A DELAY IN PROTOCOL APPROVAL Note- items checked below must correspond with the information provided in your protocol.

Note: YOU MUST NOTIFY THE HCCM WHEN YOU BEGIN WORK WITH THESE AGENTS.

Contact the HCCM Coordinator of Special Projects via phone at:

617-432-4658 or mailto:hccm@hms.harvard.edu

PI must print and sign below (mandatory; a proxy will not be accepted):

P.I Name _ P.I Signature Date / /

**MUST CHECK (X) ALL THAT APPLY**

Chemical carcinogen(s) Toxic substance(s) Radioisotope license #:

Microbiological Agent(s) COMS/PIBC #: _

Provide Biosafety Level next to each agent

Human or NHP cell line(s) or tissue(s) COMS/PIBC #: _

Non-human animal cell line(s) or tissue(s)

Other (must specify)

NONE OF THE ABOVE

This box must be checked if none of the above agents apply to your work described in this protocol.

By checking this box & signing below you are emphatically stating that you are NOT using any of the above in research animals.

Introduction

The Harvard Medical School Standing Committee on Animals was established in 1907 almost 60 years prior to the Animal Welfare Act This Committee charter states: A Committee of at least five, which has the power to inspect the animal rooms at any time, to issue orders and regulations they may deem fit for the proper care and feeding of animals, to discharge any employee of the school who in any way treats animals with cruelty, to dispose of any animal which is in any way objectionable and to determine the sources from which animals are

to be obtained This Committee shall also have general power to stop any experimental work on animals that they may consider improper or unnecessary This charter is still in effect today and the Committee, appointed

by the Dean for Academic and Clinical Programs, continues to have the authority as described

The Committee members today include scientists, veterinarians, and lay representatives This Committee is committed to the continued use of animals in research within the constraints of humane treatment as viewed

by society To justify approval of procedures, the Committee must have adequate written information regardingthe steps taken to assure humane treatment of animals Present your material clearly and concisely Lay members of the Committee must be able to understand this protocol

The Animal Experimentation Protocol (AEP) MUST include a FLOW CHART AND a written description of the procedures outlined in Section B.2 Failure to comply will result in delay of approval for an additional month

 The Deadline for submission of a New AEP, 3-Year Renewal, or Amendment is 5:00 p.m on or before the 1st business day of that month Failure to comply will result in the delay of review for an additional month You must submit an electronic (MSWord) version of your protocol

 Fax Signature pages to 617-432-3169

 Submit 3-Year Renewal two months prior to the protocol’s expiration date to avoid a lapse in research

A ANIMAL USAGE

 Place an “X” next to the procedures you will be performing

 Enter the total number of animals in each category as well as the total number in multiple categories

 Complete a separate ‘Checklist’ for each species

 Complete a search for alternatives for each procedure in Category D and/or E

Breeding colony

Housing ONLY (no other procedures)

Total number of animals to be used in Category B only

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

Simple injections (IP, IV, etc.)

Use as a parasitic host

Total number of animals to be used in Category C

Note: For all procedures in Categories D & E (below) a search must be completed in Section P

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)

Lavage

Multiple MAJOR survival surgery

Multiple MINOR survival surgery

Non-survival surgery

Physical trauma

Survival surgery: MAJOR

Survival surgery: MINOR

Tail biopsy for genotyping

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

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

justification must be included in the indicated section of the protocol and/or separate exemption form

Withholding of enrichment from singly housed animals Section D.4.c

Euthanasia methods that are not consistent with the AVMA Guidelines Section E & Exemption

Non-pharmaceutical grade drugs and other compound suspensions Section I.7

Withholding postoperative analgesia Section J.2.k & ExemptionFood/water withholding or scheduling (not ad-lib) Section N

Smaller caging than the recommended space allotment (e.g.: CLAMS) Exemption form

Deviations from housing density standards Exemption form

Deviations from the 12/12 hour light/dark cycle Section N

Any other exceptions to the standards of the PHS Policy, the Guide, or the

AWA - Please specify:

Exemption form

2 JUSTIFICATION FOR THE USE OF ANIMALS

Federal Assurances: You are required by federal law to provide the following justifications

experiments using tissue culture or computer models? If you are generating antibodies, could you use in vitro methods?)

animals is appropriate to the work being proposed Provide groups and statistical analysis to be used if relevant.)

methods to those that are less invasive):

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:

 For 3-year reviews, incorporate all procedures listed in approved amendments in the past three years, ifapplicable All amendments expire at the protocol 3-year renewal date

1 Aims and Significance: Provide a brief lay summary, no more than one page, describing your research Do

not include an excerpt from your grant proposal

manipulation (including changes in light cycle, alteration of feeding, etc DO NOT include details of in vitro work) For SURGERY, state ONLY the name of the procedure in this section Describe the surgery in detail only in Section J

a Progress Report: Briefly describe your RESULTS from the past 3 years and explain how the present

application continues this work:

b For USDA-covered species (not mice, rats, or birds), describe any unexpected animal deaths in the

course of your experiments:

c List publications and meetings in the past three years:

d Changes (briefly summarize any CHANGES in the protocol in the past three years, i.e species,

numbers, procedures, etc.):

FOR ALL (NEW and 3-YEAR Review) protocols

 Present your experiments in a flowchart format (as opposed to a table, grid, or paragraph)

 Show the schedule for the animal procedures in your flow chart, including the time points when the animals will beeuthanized, if applicable

 Include animal numbers

 For guidelines on creating your flowchart click here

 USDA covered species users note: This flowchart will be included with the medical record of each animal

Present your flowchart here:

 If the person needs to be trained, indicate who will do the training

 NOTE - ALL current personnel must sign the last page of this form, Section S to gain access to thefacilities NEPRC clinical staff members that do not have substantial, direct, intellectual contributions tothe work do not need to be listed or sign this form unless they are the PI but must sign a confirmationcompliance statement annually

 If this is a three year renewal protocol: The list below WILL REPLACE ALL CURRENT LAB

ALL PERSONNEL HANDLING ANIMALS MUST BE TRAINED IN THEIR HUMANE CARE AND USE

Records of personnel training must be maintained by the lab

State the building and room number where training records for lab personnel will be stored:

All animal users are required to complete the following AALAS Learning Library (ALL) modules before they can

be listed on an animal experimentation protocol:

 “Working with the IACUC: Non-VA version” (All researchers)

 “Safe Use of Toxic or Hazardous Materials in Animals” (NEPRC researchers should contact NEPRC for

this training)

 “Working With BL2-N Infectious Agents in Animals” (NEPRC researchers should contact NERPC for

this training)

The ALL can be accessed online at any time and courses can be completed from any location

Follow these steps to access the ALL:

• Go to http://www.aalaslearninglibrary.org/

• Click on ‘Enroll now!’ or log in to a previously created account

• Click on ‘Enroll as an Individual in a Group’

• Enter Access code: 20045HMAIACUC

• Set up your account and complete your enrollment (Institutional ID is you personal ID card number)

• To begin the courses, click on the ‘Libraries’ tab on along the top of the page and select the ‘Animal

Care and Use Courses Library’ – you will then see a list of ‘AALAS Tracks’

• From the middle of the list, select ‘HMA IACUC Courses’

• Begin reading the lessons When done, take the exams

• Upon successful passage of each exam, you may print out a certificate showing that you successfully

completed the course (click on ‘Subscriber Center’, the tab on the far right along the top, and then select ‘Personal Access’, then click on ‘My Transcript’)

D HOUSING/PROCEDURE LOCATION

WAB HSPH2 THORN HIM NEPRC NRB SGMB MCP 65 Landsdowne 180 Longwood WAB HSPH2 THORN HIM NEPRC NRB SGMB MCP 65 Landsdowne 180 Longwood

For all research using rodents, indicate the level of biosecurity that you require

Specific-pathogen-free (SPF) facilities are free from infection with a defined panel of infectious agents These areas ONLY house animals from approved vendors or those animals that have undergone HCCM quarantine Animals in SPF facilities are maintained so as to prevent infection and undergo regular serologic surveillance to assure SPF status Non-SPF facilities may harbor one or more of these pathogens

a. Provide the area(s) where your animal procedures will be performed, including euthanasia

**Animals may not remain in a lab for more than 12 hours, nor may they be housed in the lab overnight, without express approval from the IACUC.

MRI at 221 Longwood

(work may not begin at this location until PI is trained and certified for

use of human magnet)

BIDMC LSAIF imaging facility

BIDMC MRI (Non-LSAIF)

MGH/Charlestown

Transport of BL2 infected animals

(specify origin and destination)

Transport to any other institution (specify)*

None of the above

*Animal transport to any other institution requires submission of an approved IACUC protocol from that institution

a Specify the manner in which you identify your animals:

Ear notching/clipping Ear tagging Tattooing Banding Vendor-placed tag or tattoo *Toe Clipping Micro-chipping Other (Specify) Ear notching/clipping Ear tagging Tattooing Banding

Vendor-placed tag or tattoo *Toe Clipping Micro-chipping Other (Specify)

b Describe the details of your method for identifying your animals:

i Describe the procedure for identifying your animals (vendor-placed tags/tattoos excluded):

ii Age of animal at time of ID procedure (note: Analgesia may be required under certain conditions):

iii Scientific justification is required for toe-clipping All other methods of identification must first be considered State your justification here (you must contact the IACUC office to request an Exemption form):

*The HMA IACUC requires social housing of all social animals If ‘NO’, provide scientific justification for not socially housing the animals Describe what will be done to replace this social contact with conspecifics

a. Scientific justification for non-social housing of animals:

b. Methods for replacing socialization:

c. Will individually housed animals receive environmental enrichment?

d. If ‘NO’, provide scientific justification for withholding environmental enrichment:

E DISPOSITION OF ANIMALS

(Note: Any applicable endpoints noted below must be included in the flowchart in Section B)

 Cervical dislocation and guillotining without anesthesia are not acceptable unless scientifically justified and approved by the Committee

 If you are using CO2 as a means of euthanasia, you MUST use a second physical means to ensure death (ie bilateral thoracotomy, exsanguination or harvest of an essential organ, etc.)

 Dry ice is NOT AN ACCEPTABLE METHOD of euthanasia under any circumstances

 Any deviation from the AVMA Guidelines on Euthanasia must be justified below:

If you answered ‘YES’ above, you must answer the following (copy and paste the table below for each

additional species):

Species:

Method of euthanasia:

Justification for any deviation from AVMA guidelines:

Anesthetic/tranquilizing agent(s), if applicable:

Dosage:

Route of administration:

another PI) within the jurisdiction of the HMA IACUC NOTE: if your animals have had procedures performed, other than genotyping, the protocol on which the animals are being transferred to must be amended to include the animals that have undergone the prior procedure(s)

Will you be transferring any of your animals internally? Yes No

If you answered ‘YES’ above, you must contact the HCCM to fill out the appropriate transfer form from the HCCM website

If at NEPRC, please complete the Animal Protocol Transfer Request Form for INTERNAL Transfers

jurisdiction)

Will you be transferring any of your animals externally? Yes No

If receiving collaborator information is not yet available, answer “No” above and submit an External Transfer Form to the IACUC office when this information becomes available and at least one week prior to the animal transfer

If at NERPC please contact Veterinary Resources

If you answered ‘YES’ above, you must complete the following (copy and paste for each collaborator):

i Species:

ii Receiving Investigator:

iii Receiving Institution:

SHIPPING METHOD (https://arcm.med.harvard.edu/secure/export_import.htm)

Answer ONE of the following:

NOTE: animals cannot be shipped via taxi or by any other

public transportation:

I agree to ship ONLY to the Animal Resource Center at the Receiving Institution and NOT to an individual investigator or laboratory

I agree that the receiving Investigator has a current approved protocol for these animals

I agree to notify the receiving Investigator of any prior genotyping or identification procedures that have been performed on these animals

I agree to provide long-term gel-packs or equivalent if the animals will travel for more than 3 hours

Might any animals on your study by adopted at the end of the study? Yes No

If ‘YES’, you MUST contact and receive permission from the HCCM at the appropriate time to begin the

adoption process

F IMMUNIZATION

Variance and Justification

you must provide assurance that the animals will be housed on soft bedding and have easy access to food andwater

NOTE: Footpad injections are allowed in ONE FOOT PER ANIMAL and are permitted only if justification is deemed sufficient by the IACUC

Justification for footpad injection: