REGULATIONS & POLICIES REGARDING THE USE OF ANIMALS IN RESEARCH AND TEACHING Responsible Conduct of Research

Federal Regulations

Public Health Service Policy on Humane Care and Use of Laboratory Animals Enforced by the Office of Laboratory Animal Welfare (OLAW) of the National Institutes of Health (NIH) Has jurisdiction over all aspects of vertebrate animal research conducted with PHS funds Requires all institutions which accept PHS funds to have an accepted Assurance of Compliance on file with OLAW Harvard applies PHS Policy to all vertebrate animal research regardless of funding source

Assurance of Compliance Agreement between Institution and NIH’s Office of Laboratory Animal Welfare (OLAW) which assures that our program includes: a properly constituted and functioning IACUC; procedures for self-monitoring; an adequate veterinary care program; an occupational health and safety program; a personnel training program; and an environment, housing and management program for animals. Forgoes on site inspections if fully AAALAC accredited Assurance number = A

The Guide for the Care & Use of Laboratory Animals Harvard states in its Assurance that it will follow the recommendations set forth in the Guide The Guide is written in general terms Specifies desired outcomes but allows institutions to develop their own means of achieving the outcome Covers all aspect of animal care and use: Animal monitoring – vet care, daily husbandry Personnel qualifications, training and occupational health and safety Physical environment of animal housing Animal psychological well-being, procurement, transportation

The Animal Welfare Act (AWA) and Animal Welfare Regulations (AWR) Enforced by the United States Department of Agriculture (USDA) All research institutions using “covered” species (regardless of funding source) must be registered with the USDA (14-R- 0128) Conducts at least annual visits of all housing or use areas for “covered” species

Association for the Assessment and Accreditation of Laboratory Animal Care, International (AAALAC) AAALAC accreditation demonstrates an institution’s commitment to responsible animal care and use and good science; considered the “gold standard” Accreditation is voluntary Renewed every three years - involves submission of document and a site visit Maintaining FULL ACCREDITATION facilitates research awards More than 680 organizations, institutions and companies in 26 countries have earned AAALAC accreditation Harvard file No

Additional Oversight MA Fish and Wildlife Cambridge Commissioner for Laboratory Animals / City of Cambridge Ordinance City recognized loophole in federal regulations Inspects annually Upholds all federal regulations Will levy fines for any infraction that remains uncorrected

Successful Animal Care & Use Program Institutional Official (IO) Institutional Animal Care & Use Committee (IACUC) Research Administration Services IACUC support office Occupational health program Research personnel training Office of Animal Resources (OAR) PI and research staff Environmental Health & Safety (EH&S) Committee on Microbiological Safety (COMS) Embryonic Stem Cell Research Oversight (ESCRO) Committee

Institutional Official The institutional official for animal care and use is Leslie A. Kirwan, Dean for Administration and Finance for the Faculty of Arts and Sciences Makes all the decisions regarding the administrative, financial, and regulatory needs of the IACUC and the Office of Animal Resources Oversees the work of the HU/FAS Standing Committee on the Use of Animals in Research and Teaching (IACUC) and the Director of the Office of Animal Resources in cooperation with the Chairman of the HU/FAS Standing Committee on the Use of Animals in Research and Teaching

Institutional Animal Care and Use Committee (IACUC) Review and approve proposed activities involving animals in research, testing, or teaching, and significant changes to previously approved activities. Evaluate the animal care and use program and the animal facility itself at least every six months. Review any concerns about the care and use of animals at the institution. Responsible for the training, health and well-being of personnel working with animals Report to IO to make sure the institution is aware of issues affecting the animal research program.

Authority of the IACUC The USDA Animal Welfare Act and PHS Policy grant the IACUC authority: to approval proposed use animals in research, teaching or testing. Other committees or institutional officials are not allowed to approve activities involving animals in the absence of IACUC approval.not allowed to approve to suspend any activity previously approved BUT suspension power is not limited to IACUC Other institutional officials for reason of non-IACUC related issues (lack of funds, changing research priorities, etc. Members of the veterinary staff (via the Attending Veterinarian) for any procedure in progress in which the animal is clinically determined to be in unalleviated pain or distress.

IACUC Responsibilities  Ensures that animal care and use on campus is in accordance with:  The Guide for the Care & Use of Laboratory Animals  USDA Regulations (a.k.a., the Animal Welfare Act) and  Public Health Service (PHS) Policy  Accomplishes this type of oversight by:  developing policies, procedures and guidelines  assigning specific oversight tasks to professional units

Animal Experimentation Protocol (AEP)  Describes research use of animals in plain English  Emphasizes the 3 R’s:  Reduction of animal numbers,  Refinement of procedures,  Replacement of animal models with in vitro methods if possible  READ THE PROTOCOL!

Occupational Health & Safety Program  Personnel undergo a risk assessment at the time they are added to a protocol  Participation is mandatory for all personnel working with vertebrate animals  Enrollment group (HIGH or LOW) is based on RISK assessment  Occupational health nurse or physician review medical health questionnaires  Service providers are HIPAA regulated  Access to animals is conditioned on enrollment, clearance, and adequate training

Safety Reviews  All use of viral vectors and infectious agents, and creation of transgenic animal lines must be reviewed and approved by the Harvard Committee on Microbiological Safety (COMS)  All use of toxins must be reviewed by Environmental Health and Safety (EH&S)  Use of isotopes must be reviewed and licensed by the Radiation Protection Office of EH&S

Oversight of Controlled Substances  DEA license required for purchase, possession, and use  Must be stored in a DOUBLE locking safe or wall mounted cabinet  Limited access; only authorized users  Must maintain log of use  Proper disposal is required  Institutional policy for use of controlled substances appears at:  Website contains Harvard University Researchers’ Guide for Use of Controlled Substances, application, purchase request, usage log, substance inventory, and disposal requirements.

Principal Investigator Responsibilities  Ensure research staff and project is in compliance with laws and regulations  Ensure humane animal treatment  Supervise research staff  Assure safety compliance training via EH&S  Protect public and staff from research-related risks

Office of Animal Resources Unit responsible for the environmental housing and management program Centrally manages facilities and maintains oversight of satellite housing areas Provides daily care for all vertebrate species housed on campus Established polices and procedures to protect the integrity of the barrier: Central ordering policy Controlled access to animals Standard operating procedures for moving animals and equipment/supplies among labs and facilities Import and quarantine standards

Veterinary Care Program  Preventative Medicine  Survey, diagnose and prescribe treatment for animal illness including zoonosis control  Management of protocol-related disease, disability or other diseases or disorders caused by a preceding disease or injury in the same animal  Consultation on anesthesia, surgery & animal experimentation (review all protocols)  Assessment of animal well-being  Issues veterinary treatment orders regarding animal treatment and recommended euthanasia must be followed  Assures veterinary standards such as requiring that animals be treated with pharmaceutical grade agents

Personnel Requirements to Work on Animals Must be listed on an IACUC approved protocol Must be “cleared” by an occupational health professional to work with animals (achieved through enrollment in institution’s occupational health program to work with animals) Must be trained in the procedures to be performed on the animals Must complete assigned modules in the AALAS Learning Library Must undergo animal facility orientation Must attend the Course on the Humane Care and Use of Laboratory Animals

How to Report Animal Welfare Concerns  Harvard University has a “Whistle Blowing Policy.”  All calls are confidential and all allegations will be investigated. If preferred, anonymity will be observed.  Report animal welfare concerns to:  Dr. Arthur L. Lage, Director/Office of Animal Resources Institutional Attending Veterinarian or  Ellyn Lane, Director of IACUC Administration or  Leslie Kirwan, Dean of Administration and Finance for the Faculty of Arts and Sciences, Institutional Official or

Post-Approval Monitoring (PAM)  Routine semi-annual inspections Provides guidance on mandatory communication for OAR Veterinary and Animal Care Staffs to the HU/FAS IACUC regarding issues of noncompliance or complaints Animal abuse Endangerment of animals or humans Noncompliance with protocols Repeated noncompliance with IACUC/OAR policies or practice Chronic noncompliance with OAR facility procedures Animal use area infractions Use of cage based animal medical records Rounds by veterinary staff Random audits

Compliance / Noncompliance Protocol is a contract Serious or Continuing Noncompliance Animal abuse, endangerment of animals Failure to adhere to IACUC approved protocols Repeated Non-Compliance with HU/FAS IACUC/OAR Approved Research Policies or Practices Results Retraining or suspension Protocol closure Loss of funding

Individual Responsibility Working with vertebrate animals is a privilege Requires: Humane use of animals Proper planning and training Adherence to regulations Adherence to parameters of protocol Use of common sense: liken procedures to those used w/humans for perspective

Any questions?

References The Guide for the Care and of Laboratory Animals, National Academy Press, 1996 Institutional Animal Care and Use Committee Guidebook NIH Pub. No , U.S. Department of Health and Human Services. Washington, D.C. Public Health Service Policy on Humane Care and Use of Laboratory Animals. Office of Laboratory Animal Welfare, National Institutes of Health, August Animal Welfare Act and Animal Welfare Guidelines, United States Department of Agriculture, Animal Plant and Health Inspection Service, 2005 Care and Treatment of Laboratory Animals. June 14, (NIH 420), NIH Guide for Contracts, No. 7. U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research and Training. May 20, FR

ELLYN LANE DIRECTOR OF IACUC ADMINISTRATION RESEARCH ADMINISTRATION SERVICES