Animal Regulations and My Research

Ken Salleng, DVM

Director, Office of Animal Welfare Assurance

The use of animals in research is a privilege

The concern is…….

How to be responsible stewards to the animals bearing the burden of experimentation for the betterment of society

REGULATIONS – U.S. HISTORY

An article published in November 27th, 1965 Sports Illustrated Story of “ Pepper” the Dalmatian

The public was outraged! July 1965 – bill introduced to House Rep requiring dog and cat dealers be licensed and inspected by USDA. Not passed!

What do I really have to know about animal welfare regulations?

• If you receive NIH funds, you MUST comply with the “Guide for the Care and Use of Laboratory Animals”

• If using species regulated by the USDA, you MUST follow the Animal Welfare Act and Animal Welfare Regulations

• Ensure the ethical use of animals in research

Accrediting Body

• Association for the Assessment and Accreditation of Laboratory Animal Care (AAALAC), International

• If your institution is AAALAC accredited, it gives everyone a universal understanding of program quality, accountability of the humane use of animals and assurance to other institutions about the quality of care.

What animals fall under USDA regulations?

Non human primates

Animals that are not covered by the USDA

The majority of animals used in research are mice and rats

Mice of the genus Mus Rats of the genus Rattus

Covered by the “Guide” NOT covered by the AWA and AWRs

If I have questions about the animals used in research, who do I call?

Veterinarian

Who regulates animal use at the Institutional level?

• Institutional Animal Care and Use Committee (IACUC) – Composition is determined by AWA and “the

Guide” • Veterinarian with training/experience in

laboratory animal medicine • Scientist using animals • Non-affiliated member

What does the IACUC do?

• Ensures the humane care and use of animals used in research; compliance with guidelines and regulations; while maintaining the flexibility to best meet the unique needs of the institution

• Oversees the entire animal care and use program at each institution

Functions of the IACUC

• Review and approve, require modifications in (to secure approval) or withhold approval of research activities

• Ensure that procedures involving animals will avoid or minimize discomfort, distress and/or pain

• Determine that PI has considered alternatives to painful/distressful procedures

• Determine that PI has assured that activities do not unnecessarily duplicate previous experiments

How do I get approval to do my research?

• Fill out an animal protocol detailing the experimental procedures – Synopsis of what happens to each animal from

entry until removal from the experiment • Experimental protocols MUST be approved by the

Institutional Animal Care and Use Committee PRIOR to performing any procedures on the animals

Animal Use Protocols

• Written by the Principal Investigator • Contract between PI and the institution

– May be altered by modification or at the request of the IACUC

• Only work listed on the protocol and approved by the IACUC may be performed

• Involve the veterinarian in the development of the protocol

All protocols must address the 3Rs

• Reduction—Use of statistics to verify the number of animals

• Refinement—Evaluation of procedures or use of alternative procedures to ensure minimization of pain/distress (retro-orbital bleeding vs submandibular)

• Replacement—Use of a less sentient animal (lower on the phylogenetic tree)

Consideration for alternatives to the use of animals in research

• PI must perform a current search of the literature to determine if there are alternatives to the painful procedures

• Other models – Limulus polyphemus-blood cells (amebocytes) are used to make Limulus

amebocyte lysate, used for detection of bacterial endotoxins (replaces the animal model)

– Less sentient animals • Transgenic zebrafish instead of transgenic mice

Animal Use Protocols must also address:

• Pain and Distress • Use of Analgesics • Surgeries (including multiple major survival

surgeries) • Humane Endpoints • Training of Individuals listed on protocol • Euthanasia

Pain and Distress Know the normal appearance & behavior of the species you are working with:

Deviations from normal are good indicators of pain and distress

Content appearance Hunched and angry

Pain and Distress

• If the requested procedure is going to cause more than momentary pain and/or distress, you must provide appropriate analgesics (consult your veterinary staff)

Analgesic Usage

Use of analgesics/anesthetics is appropriate for procedures or PI has provided written justification for withholding them

Veterinary consult in the planning of research proposal

Analgesic Usage

• If study design does not allow for the use of analgesics, the PI MUST justify the necessity to withhold the analgesics. These are considered Category E procedures.

Aseptic Surgery

• Separate preparation sites and surgical areas (rodent) • Dedicated rooms for prep and surgery (USDA) • Instruments, gloves, suture and implanted devices

must be sterile • Surgeons must have appropriate attire

Multiple Major Survival Surgical Procedures

• Major survival surgery—invades and exposes a body cavity (or causes permanent impairment) – Joint cavity, thoracic cavity, abdominal cavity, or

cranial vault

Multiple Major Survival Surgical Procedures

No animal will be used in more than one major operative procedure from which it is allowed to recover unless: • Scientifically justified in writing • Required as routine veterinary procedure or to

protect the animal • In other special circumstances as determined

and approved by appeal to USDA.

Post-operative Care

• Must be consistent with what is in IACUC approved protocol (including timelines for monitoring and analgesic administration)

• If there are ever concerns, contact a member of the veterinary staff

Drugs

• No expired drugs may be used on survival surgical procedures!

• SOME expired drugs may be used on acute, terminal procedures

• Expired anesthetics, analgesics, euthanasia agents and emergency drugs may NEVER be used.

Humane Endpoints

• For procedures that cause pain or injury to the animal, you must indicate what clinical signs would cause you to remove the animal from the experiment and/or euthanize the animal – Specific for type of procedures you are performing – Tumor studies have some very specific endpoints

• Tumor size/mass • Tumor impedes ability to ambulate or obtain

food/water • Ulceration/necrosis of tumor

Training • Animal Welfare Act and the Guide for the Care and

Use of Animals have specific language about the training of individuals handling and performing procedures on animals.

• Training is required! Training may be web based, hands-on, or lecture

Euthanasia

• Must be consistent with AVMA recommendations to minimize stress

• For rodents: – CO2 asphyxiation

• do not combine multiple cages • Ensure death (secondary method—cervical

dislocation, thoracotomy, or decapitation) • Neonatal animals are resistant to CO2, therefore

MUST be followed with secondary method to ensure death.

Occupational Health

• Zoonotic diseases are found in some laboratory animals – Herpes B – Toxoplasmosis – Rabies

• Animal allergies are the most common health related issue in research – Protein in urine of rodents – Dander from rabbits and cats

Occupational Health

• You will need to be enrolled in the Occupational Health Program at the institution – Allergen assessment (usually a questionnaire) – Risk assessment based upon species of animal of

which you will be working • May need vaccinations (Rabies, Hepatitis, etc) • May need additional exams or testing (Herpes

B, Q-Fever, etc…)

Environmental Health and Safety

• Some hazardous materials are used in studies. The institutional environmental health and safety committees/departments must be involved in the protection of personnel.

Reporting Animal Welfare Concerns

• Mechanisms are set up at each institution to report animal welfare concerns – Independent investigation of the concern – Protected by “Whistle-blower” policy At Vanderbilt: Call OAWA directly, report via website, or directly to compliance office

Do I need to know the Animal Use Protocol?

• You MUST know the IACUC approved protocol, because that is the contract with the research institution.

• If procedures are performed which are not on the approved protocol, it is non-compliance which is a reportable event (to granting agency) – May even result in fines, repayment of portion of

grant, or all of grant

• Any Questions????