1. Use of Animals in Research, Teaching, and Testing
Silvia I. LaRue, B.S., CPIA
Director, IACUC Office
Office of V.P. for Research

2. Goals: Understanding Animal Research Regulations
Public Perspective of Animal Research
Early History of Animal Protection in the US
Federal Regulations
The Institutional Animal Care and Use Committee (IACUC)
Protocol Review Process
Relationship between animal use protocols and grants/contracts

3. Why does animal research need to be regulated?
Protection of animal subjects.
Ensure safety and well-being of subjects and personnel involved in research.
Avoid unnecessary use of animals in research.
Garner public trust in the scientific research process. Wise use of resources.
Other ethical considerations.

4. Early History of Animal Protection Legislation in the US
1641 Puritan’s Body of Liberties
1828 First Sate anti-cruelty law passed in New York
1873 First Federal legislation: “28 hour law”
1958 Humane Methods of Slaughter Act passed
1965 Disappearance of Pepper and publication of Sports Illustrated article
1966 Life Magazine Article Published: “Concentration Camp for Dogs”

5. Pepper
In the summer of 1965, a female Dalmatian was stolen from the Lakavage family in Pennsylvania.
Her story changed America.
Seven days after Pepper’s death,
Rep. Joe Resnick introduced a pet
theft bill on the House floor.

6. Life Magazine

7. Guidelines and Regulations Pertaining to the Use of Animals
United States Department of Agriculture Animal Welfare Act (CFR 9) as amended
Public Health Service Policy on Humane Care and Use of Laboratory Animals
U.S. Govt. Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research and Training
Guide for the Care and Use of Laboratory Animals
FDA (GLP studies), EPA, Endangered Species Act
Freedom of Information Act (FOIA)
Many of these regulations came into existence after widely publicized events in animal research in the mid 80s… such as Edward Taub’s monkey studies (“Silver spring” monkeys) – accused of neglect and maltreatment of animals; police raid on laboratory.
Dr. Generelli at U. Penn. Lab broken into in 1984 by ALF. Conscious baboons restrained for head injury studies
These cases sharpened public awareness of nature of animal experimentation and helped to launch PETA.

8. PHS Policy on Humane Care and Use of Laboratory Animals Health Research Extension Act PL (1985)
Intended to ensure that PHS grantees and contractors care for and use animals humanely.
Implements and supports the US Govt. Principles.
Office of Laboratory Animal Welfare (OLAW) provides oversight.
Covers all live vertebrate animals.
“The Guide for the Care and Use of Laboratory Animals” must be followed.
Animal Welfare Assurance
PHS Policy covers all vertebrate species. Any institution getting funds from PHS is required to follow the guidelines and rules for mice and rats and birds as well.

9. PHS Policy: Assurance
A written description of animal care and use program.
Qualifications, authority and responsibility of the veterinarian.
List of members of the IACUC and procedures they will follow to fulfill reqts. of PHS Policy.
Summary of training programs in humane animal care and use.
PENALTY FOR NONCOMPLIANCE: Revocation of Assurance and loss of PHS support for entire institution.
Animal Welfare Assurance NIH will not make an award for research involving live vertebrate animals unless the applicant organization and all performance sites are operating in accordance with an approved Animal Welfare Assurance and provide verification that the IACUC has reviewed and approved those sections of the application that involve use of vertebrate animals, in accordance with the requirements of the Policy

10. PHS Policy Requires Compliance with AWRs and “The Guide”
Eighth Edition – substantially revised – many additional “MUSTS” and “SHOULDS”

11. Animal Welfare Act Code of Federal Regulations, Title 9, Subchapter A, Parts 1-4
Promulgated by US Dept. of Agriculture
All research facilities that use or intend to use live animals, as defined by the regulations, in research, testing and education must comply with the AWRs.
License and registration
Enforced by USDA APHIS, AC

12. AWRs
Definition of Covered Species: Any warm-blooded animal used or intended for use in research, testing, or education except birds, rats of genus Rattus and mice of genus Mus bred for use in research; and horses and other farm animals used or intended for use in agricultural research and production.
Mice, rats, and birds are specifically exempted from the Animal Welfare Act. Can be a live or dead animal.

13. AWRs
Subpart C – sets rules for research facilities and requires compliance with standards listed in Part 3 of the Act.
Title 9, Part 3 establishes minimum standards for animal husbandry, care, treatment, and transportation.
1989 amendments set standards for exercise for dogs and psychological well-being for primates.

14. AWRs IACUC oversees humane care and use of regulated animals.
IACUC reviews protocols to ensure they comply with AWA requirements.
Animal use must consider alternative methods to replace use of animals; reduce number of animals needed; and refine procedures to minimize pain and distress (3 Rs of alternatives)

15. AWA requires search for alternatives
USDA Animal Care Policies #11 and 12
Provide written narrative of methods used and sources consulted to determine availability of alternatives
Bill Russell and Rex Burch were appointed in the 1950’s to improve the treatment of laboratory animals and originated the concepts of replacement, reduction and refinement which was published in their book. AWA requires that facilities consider these 3 R’s in their program. Thus we ask that all PIs document methods used to ascertain that no other alternatives exist. This documentation is provided in the form of literature search summaries. AWA also requires that the PI show evidence that they are not duplicating work unnecessarily.

16. Animal Care Acronyms
IACUC - Institutional Animal Care and Use Committee
USDA - United States Department of Agriculture
AWA – Animal Welfare Act
AWR/AWAR – Animal Welfare Act Regulations
OLAW – Office of Laboratory Animal Welfare – (formerly called OPRR)
PHS – Public Health Service
NIH – National Institutes of Health
Many organizations and regulations play into animal research oversight. These are a few acronyms that you will see and should be familiar with.

17. Animal Care Acronyms IO – Institutional Official *
AV – Attending Veterinarian *
HREA – Health Research Extension Act (PL )
AAALAC, Intl. - Association for the Assessment and Accreditation of Laboratory Animal Care, International
AVMA – American Veterinary Medical Assoc.
USDA: APHIS AC – Animal & Plant Health Inspection Service, Animal Care
The IO and AV are very specific titles for the university.

18. Inspection of Programs
IACUC inspects facilities and reviews program semi-annually (self-regulating) -inspection of animal facilities and laboratories -review of “program” – administrative oversight, occupational health and safety, infrastructure, training, etc.
USDA unannounced inspection by veterinary medical officer

19. What is an animal care and use program?
AAALAC Evaluations; semi-annual inspections
What are we talking about when we say Animal Care and Use Program? What are inspectors and site visitors evaluating? There are essentially 4 components to the program…
Institutional Policies, Animal environment, housing, and management, Veterinary care, Physical plant

20. Accreditation Program
AAALAC, Intl. = Assoc. for the Assessment and Accreditation of Laboratory Animal Care, Intl.
Voluntary accreditation program
Institutions apply for evaluation of their animal care and use program.
If accredited, a site visit occurs once every 3 years.
Most grant applications ask about AAALAC accreditation in the animal subjects section.

21. Animal Care and Use Committee
Institutional Official
Institutional
Animal Care and Use Committee
Attending Veterinarian
Animal Researchers and
Animal Care Staff
Structure of oversight as seen by regulatory bodies.

22. Institutional Official
Bears ultimate responsibility for program.
Authority to allocate resources needed.
Receives semi-annual and non-compliance reports from IACUC.
Appoints members of the IACUC.
Sends reports to NIH OLAW.
Melur K. “Ram” Ramasubramanian, PhD
V.P. for Research

23. Committee Composition
Members appointed by CEO.
DVM trained in laboratory animal medicine.
Practicing scientist with experience in animal research.
Non-scientist and non-affiliated members.
No more than 3 from one reporting unit.
Alternate members.
Here at UVA, the IO has the responsibility of appointing IACUC members.

24. Comparison of Requirements
Practicing scientist
Lab animal vet
Nonscientist
Nonaffiliated
PHS
Chair
(scientist)
Lab animal vet
Nonaffiliated
USDA
No more than 3 voting members from 1 administrative unit (USDA 1985)

25. Attending Veterinarian
Responsible for health and well- being of all laboratory animals used at institution.
Must have sufficient authority including access to animals and resources to manage program of veterinary care.
Oversees aspects of animal care and use to ensure program complies with the Guide.

26. IACUC Functions: General Overview
Reviews and approves protocols and modifications to protocols
Inspect facilities and reviews program semi-annually and reports to I.O.
Reviews concerns about animal care and use
Suspends activities not in compliance with AWRs and PHS Policy
Recommendations to I.O. concerning animal care and use program, facilities, or personnel training.
This is a list of the major functions of the IACUC.

27. IACUC Functions: Protocol Review
Frequency of review – PHS: 3 years
USDA: 1 year
New as of October 2019:
1. USDA regulated species and VA funding still require annual review.
2. Rodents, fish, frogs only require 3rd annual review.
UVA
1 Yr.

28. IACUC Functions: Protocol Review
Rationale & purpose of the proposed use of animals
Clear, concise & sequential description of the procedures. Must be easily understood by all members.
Consideration of alternatives to the use of animals or less invasive procedures
Justification of the species and the number to be used
Avoidance of unnecessary duplication

29. IACUC Functions: Protocol Review
Use of appropriate sedation, analgesia, anesthesia & method of euthanasia
Housing & husbandry description
Post-procedural care & consideration of humane endpoints
Training & experience of personnel
Appropriate use of hazardous materials in animal research

30. IACUC Functions: Training Researchers
Humane methods of animal maintenance and experimentation
Methods that limit use of animals or minimize distress
Proper use of anesthetics, analgesics, and tranquilizers
Methods for reporting deficiencies in care and treatment
The IACUC is responsible for insuring that the research staff is properly trained in the use of animals for research.

31. Required Reports - AWRs
Annual report; assurance that standards of care and treatment followed; PI considered alternatives to painful procedures; facility adhering to regulations and have IACUC approval for all exceptions.
Locations where animals housed and used.
#s and species used by pain and distress categories.
Prompt notification of any suspended activity.

32. Required Reports - PHS Annual report to OLAW through the I.O.
Must note significant changes in programs, facilities, or animal care and use program
Changes in IACUC membership
Dates of semi-annual IACUC inspections & Program Review
Notification with explanation of any serious or continuing non-compliance with PHS Policy or The Guide
Any suspension of activity by the IACUC

33. Grant Applications Vertebrate Animal Section
Proposed use of the animals
Justification for use of animals, choice of species, and numbers to be used
Description of veterinary care
Description of procedures for minimizing pain and distress
Description of and rationale for method of euthanasia

34. UVa’s Protocol System
If you have a program project grant, you will need information from a number of PIs and you can access them through our system. You can export the information from the applicable PIs into a spreadsheet. Note that this is real time data. All is guaranteed accurate except for the Sponsor Award information, which is submitted by the PI and not Grants/Contracts.

35. Is the IACUC required to review the grant application?
PHS Policy and NIH grants policy statement require that institution verify, before award, that IACUC has reviewed and approved components related to care and use of animals.
NOT an explicit requirement that IACUC conduct side-by-side comparisons.
Institutional responsibility for ensuring that the application/proposal and IACUC protocol are congruent.

36. Protocol Verification Form
Purpose – ACUC Office confirms PI has an active protocol on file; includes date of review and approval.
In request to ACUC Office, provide the following:
Grant PI -
Grant Title -
Protocol PI -
Protocol Title -
Protocol # -
PLAN AHEAD !!!!

38. Post Award Change in Scope
Must obtain prior approval from NIH awarding office for change in direction, type of research or training, or other significant change in aims, objectives, or purposes of approved project. NIH must be notified in advance and approve.
If these include a significant change in animal use, the IACUC must review and approve.
Post award Change of Scope The grantee must obtain prior approval from the NIH awarding office for a change in the direction, type of research or training, or other areas that constitute a significant change from the aims, objectives, or purposes of the approved project. The grantee must make the initial determination of the significance of a change and will consult with the Grants Management Officer and Project Officer as necessary.
Examples of changes considered to be significant include, but are not limited to, changes:
in the objectives of a study
from non survival to survival surgery;
resulting in greater discomfort or in a greater degree of invasiveness;
in the species or in approximate number of animals used;
in Principal Investigator;
in anesthetic agent(s) or the use or withholding of analgesics;
in the method of euthanasia; and
in the duration, frequency, or number of procedures performed on an animal.

39. Contracts/Subcontracts Outside the University
Follow the money!
What if the animal research is performed in another country? OLAW lists all domestic and foreign Assured Institutions.
The grantee always retains primary responsibility for ensuring compliance with PHS Policy (and AWA if applicable).
You may see in grant proposals, that antibody work or creation of genetically modified animals is being done by a commercial company as a subcontract within the grant. Antibody production usually requires live animals. If the company has their own IACUC (which they should), then it’s sufficient to know that the animal work has been reviewed and approved by that institution. A copy of that approval should be sent to the home institution’s IACUC office to keep on file.
When both the grantee and subcontractor hold Assurances, some latitude is allowed in determining which IACUC will review the proposal.  However, the grantee always retains primary responsibility for ensuring compliance with PHS Policy. OLAW maintains a list of domestic and foreign Assured Institutions .

40. Animal Welfare Assurance for Foreign Institutions
A collaborating foreign institution must obtain its own PHS Assurance.
Be sure you have the latest versions.

41. Inter-Institutional Collaborations
In cases of collaboration involving animal use, “the participating institutions should have a formal written understanding [e.g. a contract, memorandum of understanding (MOU), or agreement (IIA)] that addresses the responsibility for offsite animal care and use, animal ownership, and IACUC review and oversight.” Guide p. 15
The emphasis is on documentation of the agreement to prevent ambiguity in responsibilities. The ACUC Office now has a MOU form.

42. Inter-Institutional Assurance
Used by US institutions that receive PHS funds through a grant or contract award when the institution has neither its own animal care & use program facilities to house animals, nor an IACUC, and will conduct the animal activity at an Assured institution (aka “performance site”).
They are asking to use our “license” (PHS Assurance) to do their work.
Form must be signed by IO and IACUC Chair & approved by OLAW.
Provide: IIA Form, copy of grant/contract & animal work, UVA PI’s name & protocol #.

44. Reducing Administrative Burden for Researchers

45. 21st Century Cures Act
NIH, USDA and FDA to analyze, review and revise regulations and policies
Final Report completed Aug. 2019
Outcomes:
1. USDA will seek to align its continuing review requirement with NIH From annual to 3 Year Review
2. The AWA will need to be amended from current annual review requirement.
3. USDA will eliminate need for new registration every three years.
4. OLAW will review and clarify requirements of grant-to-IACUC protocol congruence.
5. OLAW and USDA will work with DoD
and VA to harmonize research
oversight.

47. ACUC Home Page Lower Section

49. Goal of regulations and oversight
Goal of regulations and oversight is not to impede important scientific research. The majority of the public recognizes that the use of animals is essential to advancing knowledge in science and medicine. The regulations are in place to ensure that this is done in a manner that is safe, humane, and uses animals judiciously.
Use of animals is essential to the advancement of knowledge in science and medicine.
This is done in a manner that ensures safe, humane, and judicious use of animals.

50. Result of regulations and oversight
Goal of regulations and oversight is not to impede important scientific research. The majority of the public recognizes that the use of animals is essential to advancing knowledge in science and medicine. The regulations are in place to ensure that this is done in a manner that is safe, humane, and uses animals judiciously.

51. Message to the scientific community
Message to the public
Message to the scientific community
Helps inform the regulatory process
This is the message that should be promoted, and that helps guide the regulatory process.

52. 924-0405 ACUC@VIRGINIA.EDU P.O. BOX 800720 COBB HALL, ROOM B001
ACUC OFFICE
P.O. BOX
COBB HALL, ROOM B001