CRA Study Session, Week 11

Presented by Cathy Berardi

National Institute of Health: Understanding cell and organ function, which is similar in all vertebrates, helps researchers design experiments to test new treatments in people.

Diagram 1: http://www.nature.com/news/2011/110223/full/470452a.html Diagram 2: http://science.education.nih.gov/AnimalResearchFS06.pdf

Poll of nearly 1,000 biomedical scientists:

Well being of the animals Ethical use of the animals Safety of researchers and administrators

involved Survey asked those conducting animal research…

http://www.nature.com/news/2011/110223/full/470452a.html

1. U.S. Department of Agriculture (USDA) Animal and Plant Health Inspection Service (APHIS)

2. Public Health Service (PHS) Office of

Laboratory Animal Welfare (OLAW)

Animal Welfare Act (AWA) ◦ Signed into law in 1966, last amended in 2007 ◦ Primary federal statute that governs the sale,

handling, transport, and use of animals in research, exhibition, commercial transport, and by dealers. ◦ Other laws and policies exist but all refer back to

the Animal Welfare Act as a minimal acceptable standard.

Operates as part of NIH, an agency of PHS Health Research Extension Act of 1985

Required Health & Human Services (HHS) to Establish guidelines to ensure the proper care and treatment

of animals used in research which must address: Appropriate use of tranquilizers, analgesics, anesthetics,

paralytics and euthanasia Appropriate pre and post surgical medical and nursing care

for animals Mandate the development of the Institutional Animal Care

and Use Committee (IACUC) Lists requirements for Animal Welfare Assurances Lists requirements for training researchers in methods that

limit the use of animals or animal distress

OLAW carries out mandates by: ◦ Implementing and interpreting the policies ◦ Negotiating Animal Welfare Assurances submitted

by institutions ◦ Evaluates compliance with the policy ◦ Educates institutions and PIs receiving support from

PHS agencies

Public Health Service/NIH: “Animals used in research” are “any live, vertebrate animal used for research, research training, biological testing, or related purposes.”

USDA/AWA: “Any live or dead dog, cat, nonhuman primate, guinea pig, hamster, rabbit, or any warm-blooded animal used for research, teaching, experimentation, or exhibition purposes, or as a pet.” Exempt from coverage are coldblooded species, birds, rats, mice bred for use in research, horses not used for research purposes, farm animals, fish and invertebrates.

1999: Petition to the USDA wanted to expand the definition of animal to include birds, rats and mice. Caused for great concern because no correlation between the cost and benefit of doing so.

2002: Resolved with the Farm Security and Rural Investment Act which eliminated research rats, mice, and birds from USDA and AWA oversight.

9 principles that provide framework for research conducted in accordance with the policy

History ◦ 1985: A set of federal principles were put together

by the Interagency Research Animal Committee ◦ 1986: Incorporated into PHS policy

1. The transportation, care, and use of animals should be in accordance with the Animal Welfare Act and other applicable Federal laws, guidelines, and policies. 2. Procedures involving animals should be designed and performed with due consideration of their relevance to human or animal health, the advancement of knowledge, or the good of society. 3. The animals selected for a procedure should be of an appropriate species and quality and the minimum number required to obtain valid results. Methods such as mathematical models, computer simulation, and in vitro biological systems should be considered. 4. Proper use of animals, including the avoidance or minimization of discomfort, distress, and pain when consistent with sound scientific practices, is imperative. Unless the contrary is established, investigators should consider that procedures that cause pain or distress in human beings may cause pain or distress in other animals. 5. Procedures with animals that may cause more than momentary or slight pain or distress should be performed with appropriate sedation, analgesia, or anesthesia. Surgical or other painful procedures should not be performed on unanesthetized animals paralyzed by chemical agents.

6. Animals that would otherwise suffer severe or chronic pain or distress that cannot be relieved should be painlessly killed at the end of the procedure or, if appropriate, during the procedure.

7. The living conditions of animals should be appropriate for their species and contribute to their health and comfort. Normally, the housing, feeding, and care of all animals used for biomedical purposes must be directed by a veterinarian or other scientist trained and experienced in the proper care, handling, and use of the species being maintained or studied. In any case, veterinary care shall be provided as indicated.

8. Investigators and other personnel shall be appropriately qualified and experienced for conducting procedures on living animals. Adequate arrangements shall be made for their in-service training, including the proper and humane care and use of laboratory animals.

9. Where exceptions are required in relation to the provisions of these Principles, the decisions should not rest with the investigators directly concerned but should be made, with due regard to Principle II, by an appropriate review group such as an institutional animal care and use committee. Such exceptions should not be made solely for the purposes of teaching or demonstration.

PHS’s principles refer to the Guide for guidance through the principles

This guide specifies an institution’s animal care and use program requirements

If any conflicts arise between the Guide and the Animal Welfare Act, the AWA shall govern

Guide has 6 sections: 1. IACUC 2. IACUC procedures 3. Veterinary care 4. Personnel qualifications and training 5. Occupational health and safety 6. Animal facilities and husbandry

To use animals in research, an institution must establish a review committee (IACUC)

The CEO of the institution to appoint the IACUC members, a minimum of 5, including: ◦ Veterinarian who has training or experience in laboratory animal science and

medicine and who has authority and responsibility for institutional activities involving animals

◦ A practicing scientist experienced in research involving animals ◦ A nonscientist member ◦ One individual not affiliated with the institution

Committee responsibilities: ◦ Review of protocols ◦ Periodic evaluations of the institutional animal care and use program ◦ Inspection of facilities

Became a requirement under PHS’s Health Research Extension Act of 1985

Policy requires that PHS must approve an institution’s assurance before it can make an award involving the use of research animals to the institution

Assurance includes: ◦ Description of institution’s program for animal care and use ◦ Designation of the institutional official responsible for compliance ◦ Institutional assurance that it will comply with the PHS policy, the

Guide for the Care and use of Laboratory Animals, and the Animal Welfare Act and implementing regulations

Proposals require: ◦ Identification of the kind and # of animals to be used ◦ Rationale for the animal use & the appropriateness of the

numbers and species used ◦ Description of the proposed use of the animals ◦ Description of the procedures designed to minimize

discomfort and injury ◦ Verification of IACUC review and approval

Just-in-time: Permits institutions to submit IACUC approval verification after peer review and prior to award.

Records subject to 3 year retention requirements: ◦ PHS approved assurance ◦ IACUC meeting minutes ◦ Records of applications, proposals, and proposed significant

changes in the care and use of animals ◦ Whether IACUC approval was given or withheld ◦ IACUC semiannual reports and recommendations ◦ Records of any accrediting body determination

Annual report to PHS includes: ◦ Any change in institution’s program for animal care and use ◦ AAALAC accreditation status ◦ Changes in Institutional Official and in IACUC membership ◦ Dates IACUC conducted semiannual evaluations ◦ Any minority views

AWA requires certain standards of animal husbandry, recordkeeping, review of research protocols and veterinary care.

Must register with APHIS and provide animals with proper treatment and a healthy and safe environment.

APHIS Form 7023: Annual report required by research facilities ◦ These reports are posted on their website following a 2005

lawsuit by the Humane Society of the United States which stated reports they had requested either were heavily edited or missing.

Designated by PHS as an accrediting body for institutional animal care and use programs

Voluntary accreditation involves the evaluation of all institutional programs and facilities for activities involving animals (and can be more strict than federal rules and regulations!)

But Why? ◦ AAALAC website: Represents Quality Promotes scientific validity Provides assurance in global marketplace Recruiting tool Demonstrates accountability Provides confidential peer review Stimulates continuous improvement

◦ May help avoid potential problems!

AWA ◦ Enforced by APHIS through annual, typically unannounced, inspections and

requires all facilities to be licensed and registered. ◦ Unfavorable inspections have opportunity to make corrections within a

given timeframe. ◦ 2005: Inspections posted online

PHS Policy on the Humane Care and Use of Laboratory Animals ◦ Enforced by OLAW through 2007 memorandum (“Memorandum of

Understanding”) ◦ Requires adherence to policy for each institution receiving PHS support

which is achieved through assurance mechanism, educational programs and OLAW site visits.

◦ Noncompliance must be corrected and continued noncompliance can result in withdrawal of an institution’s entire Assurance.

Advice from NIH’s Office of Extramural Research: In preparation…

1. Operate an impeccable program of animal care and use and maintain their animal research facilities in optimal conditions at all time.

2. Review their research portfolios to determine what activities might be targeted.

3. Make certain that their institutional security group develops relationships with local and state law enforcement before an event happens.

4. Develop a crisis management plan.

If an incident does occur… 1. Immediately contact appropriate university officials. 2. Immediately contact OLAW if the health or well-being of animals is

jeopardized. 3. Notify the project officers of granting agency.

Americans for Medical Progress (AMP) ◦ Mission: Nurtures public understanding of and support for the

humane, necessary and valuable use of animals in medicine ◦ Nonprofit funded by medical schools, public and private research

facilities, scientific societies and individuals ◦ http://www.amprogress.org/about ◦ Programs & services include: Publications & posters News stories Weekly e-newsletter Fellowships Collaborates with other research organizations to maximize resources

Animal Welfare Act and Regulations Guide for the Care and Use of Laboratory Animals U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used In

Testing, Research, and Training USDA Animal Care USDA Links to Other Sites Office of Laboratory Animal Welfare

◦ Animal Use & Management ◦ Animal Welfare Assurances ◦ Applicability of the PHS Policy ◦ Institutional Reporting to OLAW ◦ IACUC Composition, Functions & Authority ◦ Institutional Responsibilities ◦ Program Review & Inspection of Facilities ◦ Protocol Review ◦ Policy & Regulation

OLAW Useful Links Animal Welfare Information Center