UNIVERSITY OF CENTRAL MISSOURIINSTITUTIONAL ANIMAL CARE AND USE COMMITTEE PROCEDURES

Approved by Institutional Animal Care & Use Committee Spring 2013

PurposeThe University of Central Missouri’s (UCM) Institutional Animal Care and Use Committee (IACUC) is dedicated to the humane care and use of animals in activities related to research and teaching conducted at UCM or by individuals associated with the university. The IACUC is guided by federal regulations and ethical principles intended to ensure the humane care and use of animals in research and teaching. All research and teaching involving vertebrate animals that is conducted or authorized under the jurisdiction of UCM is subject to review by the IACUC.

Regulatory Authorities Governing Animal UseUCM’s IACUC policies and procedures were developed by the IACUC based upon requirements set forth by the following:

USDA under statutory law (Animal Welfare Act [7 USC, 2131-2159]) and regulations (Federal Animal Welfare Regulations [Title 9, Chapter 1, Subchapter A, Parts 1 to 4])

PHS under statutory law [42 USC 289d], the PHS Policy on Humane Care and Use of Laboratory Animals (PHS Policy), and The Guide for the Care and Use of Laboratory Animals (The Guide).

The U.S. Department of Agriculture, through its division of The Animal and Plant Health Inspection Service (APHIS), which administers the Animal Welfare Act (AWA) and its amendments, codified at 7 USC 2131 et seq. and 9 CFR 2.31 et seq. The AWA regulates the transportation, purchase, care and treatment of animals used for exhibition, sold as pets, or used in basic and biomedical research, education, and product safety testing.

The AWA requires the establishment of an IACUC at all institutions that use animals in research, teaching or testing. The IACUC is responsible for reviewing all activities that involve animals in research, teaching, or testing to ensure humane use of animals. The IACUC is also responsible for conducting semiannual assessments of the University of Central Missouri’s IACUC Policies and Procedures for animal care and use programs. As a research facility, UCM is subject to random inspections by USDA and must file an annual report concerning its IACUC Policies and Procedures. Every investigator at UCM has access to current AWA and related regulations.

The PHS Policy was created to implement the provisions of the Health Research Extension Act of 1985. The Office of Laboratory Animal Welfare (OLAW) at NIH administers the policy, which applies to institutions conducting PHS-supported projects involving live vertebrate animals.

The PHS Policy requires the institutions to establish an IACUC. In accordance with the policy, the IACUC, using The Guide, is responsible for reviewing the use of animals and conducting semiannual assessments of the UCM IACUC Policies and Procedures, including inspections of all animal research facilities.

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The University of Central Missouri is required to file an Animal Welfare Assurance of Compliance Statement (Assurance) every five years with OLAW, providing written documentation of the institution’s commitment to animal welfare and detailed information on UCM’s IACUC Policies and Procedures. The Assurance commits UCM to compliance not only with the PHS Policy and The Guide, but also with the AWA. Every investigator at UCM is accountable to review and be familiar with the contents of PHS Policy and The Guide.

Organizational StructureThe University of Central Missouri’s Institutional Animal Care and Use Committee (IACUC) reports to the Institutional Official (IO). The Institutional Animal Care and Use Committee include the committee, the Institutional Compliance Official, and clerical support.

Regulations and guidelines governing the use of laboratory animals apply to all persons at UCM involved in animal use. A quality animal care and use program requires the integrated support of many individuals at UCM, including the IACUC, IO, and Attending Veterinarian, Investigators, students and animal care staff.

The Institutional Official has the authority to legally commit, on behalf of UCM, that regulatory requirements will be met under the AWA and PHS Policy. The IO is responsible for appointing members to IACUC, and as the IO, will sign UCM’s Institutional Assurance.

The University of Central Missouri Attending Veterinarian serves on the IACUC as a voting member and has delegated authority and responsibility to implement the PHS Policy and recommendations of The Guide and the AWA. The Attending Veterinarian routinely inspects the animal facilities and all animals at UCM. The Attending Veterinarian is available to make recommendations concerning preventive health programs for animals, disease treatment, analgesia, anesthesia, post-operative recovery, euthanasia, general animal welfare, and technical training. The Attending Veterinarian provides routine veterinary care, preventive medical care, and on-call emergency care and consultation for UCM animals. The Attending Veterinarian has the authority to immediately halt activity on any protocol if animal welfare is endangered. As the Attending Veterinarian is not on campus, the animal care specialist is responsible for daily care and facility management.

IACUC Membership The IACUC consists of at least seven members, of varying professional and personal backgrounds, including at least one veterinarian, one non-scientist, one practicing scientist, and one person who is not affiliated with UCM in any way other than as a member of the IACUC (for example, a community member). The community member may be either a scientist or non-scientist. As described in the Official Charge, the (IO) of UCM appoints the committee with recommendations from the IACUC Chairperson along with nominations from the Faculty Senate Committee on Committees for specific positions with confirmation by the Faculty Senate.

IACUC Meetings and Quorum RequirementsThe committee will meet as needed to discuss / review protocols, but at a minimum of at least once per semester, to include summer if needed. A quorum is required at any meeting at which

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formal action is taken by the IACUC, and a majority vote of those present at the meeting is required for any formal action (for example, approval or suspension).

A quorum requires the presence of a majority of the current voting members of the IACUC. Members must be physically present at a meeting to be counted toward a quorum. Any member who has a conflict of interest in a matter under consideration by the IACUC (for example, is personally involved in the matter) shall not be counted toward a quorum for that portion of the meeting. If a quorum is lost at any time during the meeting, the meeting shall be adjourned and no further formal action shall be taken until a quorum is attained.

IACUC recorded minutes are intended to reflect the substantive discussion of protocols. Minutes are intended to contain sufficient information that a reasonable person could understand the nature of the discussion. According to PHS policy, IACUC minutes must reflect:

Records of Attendance Activities of the Committee Deliberations

Minutes will be reviewed by the IACUC at the following meeting and voted on for approval.

IACUC ResponsibilitiesThe IACUC has general oversight responsibility for the UCM IACUC Policies and Procedures, AOHS Program, Veterinary Care Program, and the Animal Research Facility (ARF). The ARF is defined as the basement area of the Morris building designated as such. Specific responsibilities of the IACUC include the review of animal use, inspection and review of ARF Standard Operating Procedures, Veterinary Care Program, compliance activities, record keeping and community relations.

Review of Animal Use: Review and approve, require modifications to, or withhold approval of all new

applications or modifications to existing Protocols involving animals Conduct continuing review of approved Protocols, not less than annually Conduct de novo review (similar to an initial review) of all open Protocols at least once

every three years if the PI does not wish to close the Protocol Review all Animal Incident Reports and determine whether any additional action is

necessary (see Policy R&C-IACUC-6.0 section 1.2)

Inspection and Review of Animal Research Facility’s Standard Operating Procedures: Recommend procedures to be followed for the proper care and humane treatment of

animals and review them every six months using Title 9 CFR (USDA) and The guide (OLAW) as a basis of review, providing a written report to the Institutional Official

Inspect every six months all of University of Central Missouri’s animal facilities using Title 9 CFR and The Guide as a basis of inspection, providing a written report to the Institutional Official.

Provide recommendations to the Institutional Official and Facility Director regarding any aspect of the animal program, facilities or personnel training.

Inspection and Review of Veterinary Care Program:

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Recommend procedures to be followed for the proper care and humane treatment of animals and review them every six months using Title 9 CFR (USDA) and The Guide (OLAW) as a basis of review, providing a written report to the Institutional Official.

Provide recommendations to the Institutional Official and Facility Director regarding any aspect of the animal program, facilities or personnel training.

Compliance Activities: Review and investigate noncompliance with the University of Central Missouri IACUC

Policies and Procedures, applicable regulations, PHS Policy or The Guide. Suspend any activity that is not in compliance with the PHS Policy and The Guide, the

USDA regulations, or IACUC guidelines.

Record Keeping: Maintain records of IACUC activities as required by regulation or the PHS Policy

Community Relations: Help serve as a liaison between the university and the community for matters involving

animal research and welfare.

Personnel Using Animals All individuals using live animals in the context of research or teaching, except those personnel classified as exempt are governed by regulations and policies. Personnel classified as Investigators have additional responsibilities.

Requirements for all personnel using live animals: Receive and maintain IACUC training. Follow the procedures for animal care and use described in approved Protocols Adhere to the ARF Standard Operating Procedures when using the Facility. Report noncompliant activity to the ARF Manager, IACUC Chair or Research

Compliance Officer.

Requirements for Principle Investigators: The investigators have the same responsibilities as all other personnel working with

animals. Receive and maintain responsible conduct of research training. Submit the application (see Protocol Application for Animal Use), as described in this

document and per Instructions (see Protocol Application for Animal Use Instructions), for any work involving animals and wait for approval before beginning such work.

Provide a copy of each approved Protocol to every person participating in the research project, and ensure that each person understands his/her duties as well as the project as a whole.

Ensure that all personnel on the Protocol have adequate training and/or experience to carry out their designated roles.

Be certain that all project personnel follow the procedures for animal care and use described in approved Protocols

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Request and receive approval for any modifications of animal procedures or other animal use before implementing such modifications

Request and receive IACUC approval

IACUC Education and Training

All IACUC members receive initial training on the IACUC and its procedures. Members are required to complete and maintain Collaborative Institutional Training Initiative (CITI) IACUC training every three years. Continuing education of IACUC members is through attendance at the meetings, which will include discussions of criteria for approval of proposed research, observations and suggestions by the ARF staff, changes to regulations and guidelines, results of program reviews and inspections, and questions and concerns brought to the attention of the IACUC.

The Principle Investigator is required to complete and maintain Collaborative Institutional Training Initiative (CITI) IACUC or its equivalent. All principle investigators who are students will require a faculty member to personally supervise the protocol. CITI trained personnel deemed by the Principal Investigator on the protocol to be adequately trained may work independently. CITI trained personnel who have no experience with basic animal care or research techniques must work under the personal supervision of an experienced person on the protocol until trained to work independently

Exempt personnel working with animals include laboratory or training course participants, and observers of animal use activity under the personal supervision of IACUC- approved personnel. As with all protocols, the Principal Investigator bears ultimate responsibilities for the treatment of animals by personnel working under his or her supervision. Supervisors are also responsible for providing appropriate instruction to exempt personnel on any health and safety issues and on any care and handling techniques related to animal use.

Animal Occupational Health and Safety Program

The Manager of the Environmental Health and Safety Office (EHSO) monitors the Occupational Health and Safety Program (OHSP) at UCM. This monitoring effort includes periodic inspections, distribution and review of Occupational Health Risk Assessment check-up forms, and review of any incident reports. Developmental and operational oversight of UCM's OHSP is a collaborative effort between IACUC, EHSO, Safety Science Department, Human Resources, and the University Health Center. The OHSP at UCM is based on a comprehensive risk and hazard assessment accounting for the current types of research activities and animals used in research/care. Members of the Safety Science Department performed this assessment, which is reviewed annually by EHSO during one of their inspections. During the annual review an updated list of SOPs, research activities, and animals housed will be considered when reviewing the adequacy of the current facility design, available safety equipment, and available personal protection equipment.

Enrollment in UCM's OHSP is determined by the research safety training level required, which

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is organized in two tiers: Level A and B. All individuals that work in the animal care facility or have repetitive involvement in IACUC approved research must obtain Level A training, which includes enrollment in the OHSP. All individuals that plan to enter the animal care facility or participate in an IACUC approved research activity on rare occasion, or as part of a UCM lab course, must complete Level B training and be accompanied by a Level A trained individual.

Level A training: Individuals must, 1) read a document titled "Occupational Hazards Associated with Care and Use of Research Animals," 2) complete the Collaborative Institutional Training Initiative (CIT!) modules required within the courses titled either "Wildlife Research-Basic Course" or "Working with IACUC" depending on the nature of the research involved (guidance provided by IACUC chair after initial review), and 3) enroll in the OHSP. The required modules included training in the area of allergens and zoonoses. Enrollment into the OHSP is initiated by completing the "Occupational Health Risk Assessment" form, which is submitted to the UCM Health Center for evaluation and determination of required preventative health measures and monitoring program to assure worker health. Special consideration is provided for identification of precautions required for pregnant women, ill, and immuno-compromised individuals, as well as identification of individuals that will be exposed to allergens or zoonoses. The Director of the University Health Center will train all individuals enrolled in the OHSP on the precautions to be taken during personnel pregnancy, illness, or decreased immunocompetence, and furthermore communicate any needs or requirements to the individual and back to the appropriate office (Le., IACUC, EHSO, or Human Resources) when necessary. After the first year of entrance into the OHSP, individuals will be sent an "Occupational Health Risk Assessment Check-Up" form from EHSO to determine if additional monitoring or action is desired/needed. All required vaccinations are provided at the University Health Center or through a personal physician. All individuals that work in the animal care facility will be provided a tetanus vaccination through the University Health Center or through a personal physician.

Level B training: Individuals must read the abbreviated document titled "Introduction to Occupational Hazards Associated with Care and Use of Research Animals," and be accompanied by a Level A trained individual during their time within the animal care facility or performing research on animals. Institutional policies are in place for personal hygiene, handling of Hazardous agents, and personnel protection equipment and can be found contained within the Policy Guide (https://www.ucmo.edulosp/resources/...l2014 osp policies.docx) in support of OSPRI.

All animal research and animal care personnel are expected to use good personal hygiene as outlined in the Level A and B training materials. The university will supply, and maintain the cleanliness of suitable attire and PPE for use in the animal facility and laboratories in which animals are used. Any outer garments worn in the animal rooms will not be worn outside the animal facility unless another layer covers those items. There is no eating, drinking, use of cosmetics, or handling of contact lenses in rooms and laboratories where animals are housed or used. Furthermore, there is no smoking on our entire campus, including animal-use spaces. Before handling hazardous materials all personnel will be trained according to the six main objectives (i.e., potential hazards, personal protection equipment, limitations of protective

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equipment, emergency preparedness, job responsibilities, and hands-on-experience with required techniques) as outlined in the "Environmental Management Program Policy and Procedures" manual (http://webedit.ucmo.edulpslhealthlEnvironmental Management Program. pdt). After initial training, a refresher training is required annually for individuals with continued use of hazardous materials.

Official accident procedures were developed by UCM in 2001 and are posted on the website (http://www.ucmo.edu/ps/health/accident.cfm).This procedure will serve to officially report the injury and direct individuals that have sustained bites, scratches, illness, or injury while performing animal care or research to the appropriate medical professionals. If any employee is injured on the job, contact Public Safety at 4123. If an employee injury is serious and requires immediate medical attention, contact Public Safety by calling 911. Public Safety personnel will respond to assist the employee and their supervisor. Police officers will respond immediately to emergency medical needs. Safety Services personnel will respond to assist the employee and supervisor in completing the new Employee Injury Report, which Safety Services will bring with them, and to provide the employee with necessary information regarding Worker's Compensation procedures. All injuries will be treated at the University Health Center or a local hospital.

PROTOCOL REVIEW PROCESS AND PROCEDURESThe process for reviewing and approving animal use is described in this section.

Activities Requiring IACUC ApprovalThe following activities involving live animals must be approved by the IACUC before any action is initiated:

UCM Facilities – All research, teaching, biological testing projects and breeding work conducted by anyone at UCM regardless of the source of funding. Exception to this includes the UCM farms which house animals for agricultural and agricultural education purposes only. In cases in which external (non-UCM) investigators wish to use UCM research facilities on a limited basis, UCM’s IACUC may accept an approved animal use protocol from the external investigator’s PHS-approved institution in place of a UCM Protocol.

UCM Personnel – All research, teaching, biological testing projects and breeding work conducted at another institution or elsewhere by faculty, students, staff, or other representatives of UCM in connection with the investigator’s institutional responsibilities. The IACUC may accept oversight of the animal use by another PHS-approved IACUC.

The following activities involving animals do not require IACUC approval: The study of animals in their natural habitat without investigator intervention; The study of preserved specimens or tissues obtained from recognized vendors of

scientific supplies, research institutions or museums; The study of tissues obtained from a USDA-approved slaughterhouse or any vendor

selling such tissue; Any activities not associated with teaching or research.

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Types of ReviewThe IACUC uses two mechanisms for reviewing Applications and Protocols. These are Full Committee Review and Designated Member Review.

Full Committee Review (FCR)Full Committee Reviews are conducted by a quorum of members at an IACUC meeting. Any action by the committee following review requires a majority vote by those members present. In addition, items that were assigned to Designated Member Review (DMR) will be reviewed by Full Committee Review if the item is not approved by all DMR or if any DMR has requested Full Committee Review.

Full Committee Reviews are used in the following capacities: Initial Application Review – All applications are subject to Full Committee Review on

initial submission. Tabled Application Review – Applications designated “Tabled” after initial review are

subject to Full Committee Review on resubmission. Review of Significant Modification to an Approved Protocol – Modifications or

amendments to approved Protocols that are classified as Significant will be - reviewed by the full IACUC if requested by the Principal Investigator or an IACUC member. If a Full Committee Review is requested, then the request will normally be reviewed at the IACUC meeting following the next regular Protocol submission deadline.

Continuing Review of Open Protocol – All open Protocols must be reviewed on an annual basis, initially by full committee.

Renewal Review – Requests for Protocol renewal are reviewed as a new Protocol Application.

Expedited Review – Requests for Expedited Review are considered when extraordinary circumstances require that any of the above review activities occur sooner than would occur under the normal review process.

Full committee review (FCR) may result in an outcome of approve, require modifications (to secure approval), or withhold approval. When modifications are required (to secure approval), the IACUC may vote to have the revised research protocol reviewed and approved by designated member review (DMR) or returned for full committee review (FCR) at a convened meeting. If electing to use DMR, all members, including the members not present at the meeting, must have the revised research protocol available to them and must have the opportunity to call for FCR. A DMR may be conducted only if all members of the committee have had the opportunity to request FCR and none have done so. In that case, the IACUC Chairperson will appoint one or more appropriately qualified IACUC members to serve as the designated reviewer(s).  All DMR’s will review identical copies of the protocol and any decisions must be unanimous. Designated review may result in approval, a requirement for modifications (to secure approval), or referral to the full committee for review.  Designated review may not result in withholding of approval. IACUC approval must be obtained before any protocol can be implemented.

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Expedited protocol review may be necessary if research is to begin prior to a scheduled committee meeting. In this case, the protocol will be emailed to all members for their review and they will then have the opportunity to call for a FCR. If no member desires a FCR, then a DMR will be performed according to the description above.

Designated Member Review (DMR)Some review activities of the IACUC may be carried out by one or more Designated Reviewer(s)(DR) without a formal meeting of the full IACUC. Designated Member Reviews may take place at any time, and are used in the following capacities:

Revised Application Review – After initial review by Full Committee Review of a new or renewal application, the IACUC may assign Designated Reviewer(s) to review revisions after the committee votes to categorize an Application as “Revision Required to Secure Approval.”

Review of Significant Modification to an Approved Protocol – Requests for changes in approved Protocols that are defined as Significant Modifications according to policies will be distributed to the IACUC members. IACUC members will have three working days from the date of notification the request has been posted to review the modifications. Any IACUC member who wants to request Full Committee Review or to be a Designated Reviewer must inform the Chair within this time period. If there is no request for Full Committee Review, the Chair will designate one or more Designated Reviewer(s). Minor (i.e., non-significant) modifications to open Protocols can be approved by the Chair or his/her designee without notification of the full committee.

Continuing Review of Open Protocol – After continuing annual review of an open Protocol, one or more Designated Reviewers may be assigned to review revisions to Continuing Reviews for which the committee has requested additional information required to secure approval

Designated Reviewers have authority to approve, require revision to secure approval, or requestFull Committee Review for an item. The Designated Reviewer(s) may consult with additional individuals as part of the review process. A unanimous decision is required of all the Designated Reviewers before approval will be granted. If there are any questions or requests for revision, then aPrimary Designated Reviewer communicates the concerns to the investigator. Revised applications are posted for all reviewers as above and all reviewers’ comments collected until there is unanimous approval by all Designated Reviewers or there is a request for Full Committee Review. If the Principal Investigator cannot revise the Application to the satisfaction of all the Designated Reviewer(s), it defaults to Full Committee Review and is considered at the next scheduled committee meeting. The Chair will notify the Principal Investigator in writing of the reasons for the decision. The Principal Investigator may respond with further clarification or revision. Designated Reviewers other than the Chair must notify the Chair of their review decisions in writing.

Categories of Animal UseIACUC categorizes animal use based on the purpose of the animal use and the extent of pain, discomfort or distress anticipated for the animals. Additional information on these four categories can be found in the application instructions. The categories parallel USDA designations:

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Category B – Breeding that involves no procedures or functional deficits that may cause more than momentary or slight pain, discomfort or distress.

Category C – Research or teaching that involves no procedure or functional deficits that may cause more than momentary or slight pain, discomfort or distress.

Category D – Research, teaching or breeding that has the potential to cause more than momentary slight pain, discomfort or distress that will be alleviated with appropriate anesthesia, analgesia or tranquilizers; and/or that involves chronic maintenance of animals with a minor to moderate functional deficit.

Category E – Research, teaching or breeding involving more than momentary pain, discomfort or distress that cannot or will not be alleviated through the administration of appropriate anesthetics, analgesics, or tranquilizers; and/or that involves chronic maintenance of animals with a severe functional deficit.

Review CriteriaFederal requirements state that the IACUC review proposals for animal use must be based on the following criteria:

Potential Value of the Study – Activities involving live animals are designed and performed with the reasonable expectation that such use of animals will contribute to the enhancement of human or animal health, the advancement of knowledge or the good of society (PHS Policy).

Selection of Animal Species – The animals selected are of an appropriate species and the number of animals requested is the minimum number needed to obtain valid results (PHS Policy).

Minimization of Pain and Distress:o Procedures with animals will avoid or minimize discomfort, distress and pain to

the animals, consistent with sound research design [9 CFR 2.31(d)(1)(i) and PHS Policy, Section IV.C.1.a].

o Procedures that may cause more than momentary or slight pain or distress to the animals will be performed with appropriate sedation, analgesia or anesthesia, unless the Principal Investigator justifies, in writing, the scientific reasons that the procedure must be performed without such treatments [9 CFR 2.31(d)(1)(iv)(A) and PHS Policy, Section IV.C.1.b].

o The Principal Investigator has consulted with the Attending Veterinarian or his/her designee in planning procedures that may cause more than momentary or slight pain or distress to the animals [9 CFR 2.31(d)(1)(iv)(B)].

o Procedures that cause more than momentary or slight pain and/or distress to the animals will not include the use of paralytics without anesthesia [9 CFR 2.31(d)(1)(iv)(C)].

o Animals that would otherwise experience severe or chronic pain or distress that cannot be relieved will be humanely euthanized at the end of the procedure, or if appropriate, during the procedure [9 CFR 2.31(d)(1)(v) and PHS Policy, Section IV.C.1.c].

Alternatives – The Principal Investigator has considered alternatives to procedures that may cause more than momentary or slight pain and has provided a written narrative description of the methods and sources used to determine that alternatives are not available [9 CFR 2.31(d)(1)(ii)].

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Duplication – The Principal Investigator has provided written assurance that proposed activities involving animals does not unnecessarily duplicate previous experiments [9 CFR 2.31(d)(1)(iii)].

Living Conditions and Housing – Animal living conditions and housing are appropriate for the species and contribute to the health and comfort of the animals [9 CFR 2.31(d)(1)(vi) and PHS Policy, Section IV.C.1.d].

Personnel – Personnel conducting procedures will be appropriately qualified and trained in those procedures [9 CFR 2.31(d)(1)(iii) and PHS Policy, Section IV.C.1.f].

Surgery:o Activities that involve surgery include appropriate provision for pre- and post-

operative care of the animals in accordance with established veterinary medical and nursing practices [9 CFR 2.31(d)(1)(ix)].

o No animal will be used in more than one major operative procedure from which it is allowed to recover unless it is:

Justified for scientific reasons in writing by the Principal Investigator, or Required as routine veterinary procedure or to protect the health or well-

being of the animal as determined by the Attending Veterinarian [9 CFR 2.31(d)(1)(x)].

Euthanasia – Methods of euthanasia must be consistent with the most recent Report of the American Veterinary Medical Association Guidelines on Euthanasia, unless a deviation is justified for scientific reasons in writing by the Principal Investigator [9 CFR 2.31(d)(1)(xi) and PHS Policy, Section IV.C.1.g].

Review ProcessTwo primary forms are used by IACUC for reviewing animal use:

Animal Use Protocol Application (the Application) – The application must be used for new projects, significant revisions to existing Protocols, and Protocol renewals.

Animal Protocol Continuing Review Form (Continuing Review Form) – The continuing review form must be used to submit information for continuing IACUC review of previously approved projects, which occurs at least annually for each approved Protocol.

The Application and Instructions along with the Continuing Review form are available on the IACUC website.

New Protocol Application

Submitting the Application - An Application must be completed for any new project involving animal use. All correspondence regarding the application should include the Protocol title.

Requirements for Application Review - All applicable sections of the Application must be completed in full. All personnel listed on the Application must have IACUC Certification.

Processing the Application – Upon receipt of the Application by the IACUC Office: The application is processed and an IACUC file made. The proposal is placed on the agenda for consideration at the next IACUC meeting.

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The application is made available to all members of the IACUC, either electronically or on paper, at least one week prior to the meeting at which the application will be reviewed.

The Chair or his/her designee, in consultation with the other IACUC members, may provide the Principal Investigator with a list of initial concerns or questions about the application prior to the IACUC meeting. The Principal Investigator may then, if desired, make changes in the application prior to the meeting to improve the likelihood of approval. If such a revised application is submitted, it is made available to all members of the IACUC, either electronically or on paper, prior to the meeting;

The Principal Investigator may be asked to discuss the application at the meeting at which the application will be considered.

Principal Investigators may also request to speak at the meeting.

Reviewing the Application - Applications are considered for approval during regularlyscheduled meetings of the full IACUC, unless Expedited Review is requested and granted. If Expedited Review is granted, the application will be considered during a meeting called specifically for that purpose. No member may participate in the IACUC review or approval of a research project in which the member has a conflicting interest except to provide information requested by the IACUC; nor may a member who has a conflicting interest contribute to the constitution of a quorum. In all cases, a quorum of the IACUC must be present when initially reviewing any Application. During the meeting, the IACUC members decide the action to be taken on the Application. Reviewed Applications will be assigned to one of the following five categories, based on a majority vote of the IACUC members present:

Approved - The Application is approved as presented with no revisions required. The PI will be asked to sign a copy of the Application, and the Chair and Attending Veterinarian will sign the Application. The Chair will provide the Principal Investigator with a signed IACUC approval letter. For activities funded by an external agency, the Principal Investigator bears the responsibility of forwarding the IACUC approval information to the agency.

Revision Required to Secure Approval - The Application is not approved because revisions are required to make the Protocol acceptable to the IACUC. If no member requests Full Committee Review of the revised Application, the Chair designates one or more members to review the revision. The Chair or a Designated Reviewer will notify the Principal Investigator in writing of the required revisions. After a revised version of the application and an accompanying memo describing the revisions have been received by the IACUC, they are reviewed by the Designated Reviewer(s) unless Full Committee Review has been requested. The Designated Reviewers post comments on the revised version for all reviewers to read. The Designated Reviewer(s) has the authority to approve, require further revisions of, or request Full Committee Review of the revised application. If the revised Application is approved by all Designated Reviewers, the Principal Investigator will be asked to sign a copy of the Application, the Chair and the Attending Veterinarian will sign the Application, and the Chair will provide the Principal Investigator with a signed IACUC approval letter. A unanimous decision is required of all the Designated Reviewers before approval will be granted. If there are any questions or requests for revision, then a Primary Designated Reviewer communicates the concerns to the investigator. Revised applications are posted for all reviewers as above and all reviewers’ comments collected until there is unanimous approval by all Designated Reviewers or there is a request for Full Committee Review. If the Principal Investigator cannot revise the application to the satisfaction of all the Designated Reviewer(s), it defaults to Full Committee Review and is considered at the next scheduled committee meeting.

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The Chair will notify the Principal Investigator in writing of the reasons for the decision. The Principal Investigator may respond with further clarification or revision.

Tabled – The IACUC requires substantial additional information and/or has significant concerns about the Application, such that Full Committee Review of a revised Application is required. The Chair or his/her designee will notify the Principal Investigator in writing of the decision and will arrange to discuss the Application with the investigator. Before the IACUC review can continue, the Principal Investigator must revise and resubmit the application clearly identifying changes. In addition, the Principal Investigator must provide a separate cover letter to the IACUC specifically responding to each item listed in the notice of the decision to table the Application. Review of the revised Application may result in any of the outcomes described in this section.

Disapproved – The Application is not approved and the IACUC will not review a modified version of the Application. The Chair will notify the Principal Investigator in writing if the Application is disapproved, providing the basis for the IACUC decision. If an Application is disapproved, the Principal Investigator is given the opportunity to respond in person or in writing regarding the decisions made by the IACUC. The IACUC may, at its discretion, obtain external review of the Application by a PHS-approved IACUC of an equivalent institution and/or by expert consultants in the field of that research. The University of Central Missouri IACUC, however, shall be the final authority in determining the acceptability of the Application.

Decline to Review – Where the Application has significant deficiencies in information, or where the Principal Investigator has failed to follow the Instructions for completing the Application, or in other similar situations, the IACUC will return the Application to the Principal Investigator with an indication of why the Application was not reviewed. In those situations, the PI is encouraged to discuss the Application with the IACUC Chair or his/her designee to receive assistance in correcting the deficiencies.

Applications classified as Revision Required or Tabled must be revised within six months of receipt of the letter of notification, or the Application will be considered withdrawn. Protocols are valid from the date of Approval for a maximum of three years and are subject to Continuing Review on at least an annual basis.

Modifications to an Approved Protocol

Approved Protocols grant permission to conduct only those activities listed in the Protocol,conducted in the manner described, by the individuals listed, with no more than the number ofanimals indicated in the Protocol. Any changes in procedures, personnel, endpoints, care or useof additional animals require IACUC approval before the changes are implemented.

The IACUC recognizes two general classes of modification to open Protocols: Significant modifications – Significant modifications are those that require careful

review by one or more IACUC members to determine whether potential changes will affect animal welfare, and if so whether the changes are appropriately justified. These modifications include (but are not limited to):

o Changes in the objectives of a studyo Changes in surgical procedures, including a switch from non-survival to survival

surgery

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o Changes in the degree of invasiveness of a procedure or discomfort to an animalo Changes in the duration, frequency or number of procedures performed on an

animalo Changes in anesthetic agent(s)o Changes in the use or withholding of analgesicso Changes in methods of euthanasiao Changes in species, or in the number of animals used by more than 10 percento Changes in key personnel

Minor Modifications – Minor modifications are those that involve only small changes in animal numbers or procedures and thus have limited potential to affect animal welfare, or those that are administrative in nature. These modifications include but are not limited to:

o Changes in animal use locationo Changes in mailing addresses, phone numbers, and email addresseso Changes in or addition of funding sourceso Increases in animal numbers by no more than 10 percento Addition of another strain of the same animal species (if total numbers change by

no more than 10 percent)o Changes in the sex of animals to be usedo Changes in the timing of sampling procedures

The Principal Investigator is encouraged to consult with the IACUC Office or Chair for assistance in determining the category into which a proposed modification falls.

Proposed modifications should be prepared by making changes to all relevant sections of the last approved version of the Protocol, and then providing a brief summary of these changes and the reason for them on the Protocol’s cover page. Requested modifications should be reflected wherever appropriate in the Protocol. (For example, adding a new procedure may require changes to the duties of project staff, the category of Pain and Distress, objectives, experimental design, number of animals, etc., as well as the addition of the new procedure itself.) The modified Protocol should be submitted electronically, preferably in Microsoft Word format as this facilitates identification of changes made in the modification request.

The IACUC Chair or his/her designee will determine the class of the modification requested.Significant modifications enter the Designated Member Review process, with at least oneDesignated Reviewer being assigned by the Chair if no IACUC member requests to be a reviewer or request full committee review. In cases in which extensive modifications are requested by the Principal Investigator, the Chair or another IACUC member may request FullCommittee Review– in this case, the request should be submitted before the next regular Application submission deadline to ensure review at the next IACUC meeting.

Minor modifications do not undergo Designated Member Review, but are reviewed by the Chair or his/her designee without notification of all IACUC members.A request for Protocol modification may result in:

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Approval – The modified Protocol is approved as submitted and replaces the previous version of the Protocol on the date of approval. In the case of Designated Member Review, approval must be given by all individuals acting as Designated Reviewers. If approved, the PI will be asked to sign a copy of the Application, the Chair will sign the Application, and the Chair will provide the Principal Investigator with a signed IACUC approval letter. Approval of a modification does not alter the expiration date of a Protocol.

Revision Required to Secure Approval - The requested modification is not approved because revisions are required to make the modified Protocol acceptable to the IACUC. The Chair or a Designated Reviewer will notify the Principal Investigator of the required revisions. After a revised version of the modified Protocol has been received by the IACUC, the revision is reviewed by the same members who conducted the previous review.

Disapproved - The requested modification is not approved and will not be reconsidered by the IACUC. The Chair informs the investigators by written notification of the reasons for its decision and the investigator is given an opportunity to respond in person or in writing regarding the decisions made by the IACUC. No animals may be procured or used for experimentation without an approved protocol on file with the IACUC.

Continuing Review

Conduct continuing review of each previously approved, ongoing activity covered by PHS Policy at appropriate intervals as determined by the IACUC, including a complete review in accordance with the PHS Policy IV.C.1-4 at least once every three years. The IACUC procedures for conducting continuing reviews are as follows:

Facilities staff conducts a daily inspection of animal micro and macro habitat as part of our general post-approval monitoring (PAM) program. Condition of animals as well as care procedures are recorded during this inspection. In the case of field studies, site inspections for animals housed or confined for 12 hours or longer are conducted.

All researchers will be sent a protocol update survey by the IACUC on the anniversary of their initial approval date, which they must indicate any amendments to future protocols and any adverse or unanticipated events. Even if the researchers have nothing to report they must selected that option and return the form to IACUC if the protocol is to remain open. If the investigator fails to respond to the PAM request, the protocol will be placed on Administrative Hold, effective on the one-year anniversary of the Protocol’s initial approval. The protocol will then be subject to a FCR by the IACUC at the next scheduled meeting. The purpose of this Continuing Review is to provide the IACUC with current information concerning the status of Protocols.

In addition to PAM, a complete de novo review by FCR or DMR (as described in part III.D.6) is conducted in accordance with PHS policy IV.C.1-4 at least once every three years.

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All animal protocols must be re-approved by the IACUC annually if the protocol is to remain open. The purpose of this Continuing Review is to provide the IACUC with current information concerning the status of Protocols. The IACUC therefore conducts Continuing Review of eachProtocol during the last regularly scheduled IACUC meeting that falls before the one-year anniversary of the Protocol’s initial approval or most recent Continuing Review approval. Upon receipt of a completed Continuing Review form by the IACUC Office, copies are distributed to each member of the IACUC at least one week prior to the meeting at which the Protocol will be reviewed.

If the Principal Investigator does not return the Continuing Review form, the IACUC will conduct Continuing Review of the Protocol understanding there are no changes. If Continuing Review cannot be conducted for this reason, or if continued activity of the Protocol is not approved by the IACUC, the Protocol will be placed on Administrative Hold by the IACUC, effective on the one-year anniversary of the Protocol’s initial approval or most recent Continuing Review approval, and no further activities can be undertaken with animals until the IACUC approves continued activity. Administrative Hold status normally has a limit of one month. If Continuing Review cannot be conducted or continued activity cannot be approved before the end of the Administrative Hold period, the Protocol will be closed.

The IACUC conducts Continuing Review at a regularly scheduled meeting and takes one of the following actions:

Approved – The IACUC approves continued activity under the Protocol. The Chair and the Attending Veterinarian sign the Continuing Review form and the IACUC Senior Technical Specialist sends a copy of the signed form to the Principal Investigator for his/her records.

Additional Information Required to Secure Approval – Insufficient or unclear information prevents the IACUC from conducting its Continuing Review. The Chair will notify the Principal Investigator in writing of the required clarification or elaboration.After the requested information has been received by the IACUC, Continuing Review will be conducted by Designated Member Review. The Designated Reviewer(s) has the authority to approve continued activity, require further clarification of the Continuing Review materials, or request Full Committee Review of the revised Continuing Review material. If the revised Protocol is approved by all Designated Reviewer, the Chair and the Attending Veterinarian will sign the Continuing Review form and send a copy of the signed form to the Principal Investigator for his/her records. If approval does not occur by the one-year anniversary of the last approval date, the Protocol is placed on Administrative Hold.

Tabled – The IACUC requires substantial additional information and/or has one more significant concern about the Protocol, such that Full Committee Review of Protocol continuation is required. The Chair will notify the Principal Investigator in writing of the decision, indicating what additional information or action is required before continued activity under the Protocol can be approved. If approval does not occur by the one-year anniversary of the last approval date, the Protocol is placed on Administrative Hold.

Disapproved - If the IACUC does not approve continuation of the Protocol, the Chair will notify the Principal Investigator in writing of the IACUC decision, indicating what

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issues resulted in the disapproval of continued activity. If the Principal Investigator wishes to submit a modified Protocol, it must be submitted as a de novo Application and will be evaluated as such. If an Application with a modified Protocol is submitted, the disapproved Protocol will be put on Administrative Hold on the one-year anniversary of the last approval date. If a modified Protocol is not submitted, the disapproved Protocol will be closed on the one-year anniversary of the last approval date.

Renewal

Once a Protocol reaches its expiration date, it is closed and no further activities can be conducted with animals under that Protocol. Therefore if work covered by an open Protocol is expected to continue beyond its current expiration date, the Principal Investigator must submit a completeApplication on the current form to IACUC Office. Because the earliest date that Protocol renewal can be approved is the date of the IACUC meeting, and any required revisions may delay the approval date further, investigators are strongly encouraged to submit renewal Applications for ongoing projects in time for review at a meeting at least two months prior to the expiration date of the current Protocol. The IACUC reviews a renewal Application in the same manner as an original new submission. If the Protocol renewal is approved before the original Protocol expires, all animals on the expiring Protocol will be transferred to the new Protocol and covered activities can continue. If the Protocol renewal is not approved before the original Protocol expires, all activity under the Protocol must cease when the Protocol closes.

Expedited Review

Requests for Expedited Review are considered when extraordinary circumstances require that any of the above review activities occur sooner than would occur under the normal review process. The granting of an Expedited Review is rare. Missing a regular submittal deadline is not in itself sufficient reason to request an Expedited Review. The Expedited Review process includes the following steps:

Written Request – The Principal Investigator must submit a written request forExpedited Review along with a completed Protocol Application for Animal Use formor Continuing Review Form, as appropriate, to the IACUC Office.

Determination – When the request for Expedited Review is received, the IACUC Chair or his/her designee will confer with the Attending Veterinarian and another member of the IACUC to determine if the request has merit. The Chair will notify the Principal Investigator of the determination. If the request for Expedited Review is not granted, the review activity will take place via the standard procedure.

Emergency Meeting – If the request for Expedited Review is granted, the IACUC Office will convene an emergency meeting of the IACUC, which the Principal Investigator must attend. The PI must ensure the Application and other materials are received by all IACUC members prior to the meeting. A quorum of IACUC members must be present at the meeting, and a majority vote is required for any formal action (for example, approval, and request for revision to secure approval).

External Protocols

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When all animal housing and use by UCM personnel is conducted at another institution, the IACUC may recognize the animal care and compliance oversight provided by that institution’s IACUC or equivalent body. If the participation of UCM personnel in the project is in a capacity other than as the Principal Investigator, and if the supporting grant(s) are not held by university personnel, the IACUC will accept oversight by the other institution without formal verification. If UCM personnel are participating in the capacity of Principal Investigator or hold supporting grants, then IACUC will require either verified oversight by the other institution or will oversee activities directly.

The IACUC may recognize the oversight provided by AAALAC-accredited institutions. If the investigator requires the IACUC to verify the grant and protocol for federal funding agencies, then the following must be on file with the University of Central Missouri:

A current memorandum of understanding between UCM and the other institution The animal use protocol approved by the institution The letter of approval for the protocol from the institution’s IACUC

For PHS-approved or foreign institutions that are not AAALAC-accredited, IACUC must review the institution’s policies and procedures in order to determine whether UCM will accept the oversight of animal activities provided by the institution. This review will be conducted following the general procedures of Designated Member Review. The IACUC will not accept oversight by U.S. institutions that are not PHS-approved.

Comparison of Grant Proposals to Protocols

The University of Central Missouri is required by the PHS Policy to verify that the IACUC has reviewed any procedure in a PHS grant proposal that involves the care and use of animals. In order for UCM to provide the required verification, the grant proposal must be compared with one or more IACUC-approved animal use Protocols.

At the time of grant proposal submission, Grants Administration will request that the Principal Investigator identify the IACUC-approved animal use Protocol(s) that contain the procedures in the grant proposal. The title of the Protocol(s) does not have to match that of the grant proposal, and one grant may be covered by multiple Protocols and vice-versa. However all research in aPHS grant that involves animals must be included in an approved IACUC Protocol(s). GrantsAdministration will submit the grant proposal and the Protocol title to the IACUC Chair or the Chair’s designee, who compares the description provided in Section F “VertebrateAnimals” (or its equivalent) of the grant proposal to the approved IACUC Protocol(s) for consistency in:

Overall scope of the animal work Proposed animal models (including species and strain) Estimated number of animals Procedures performed on live animals

If Section F "Vertebrate Animals" (or its equivalent) of the grant proposal and the approvedIACUC Protocol(s) are consistent, the IACUC Chair or the Chair’s designee will inform Grants Administration, who will communicate the verification to the federal granting agency. If the

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grant proposal and Protocol(s) are not consistent, the Principal Investigator must resolve the discrepancy.

Reporting and Record Keeping by Project Personnel

All personnel working with animals are required to report any unapproved activities or any unexpected events that may compromise animal welfare. In addition, certain procedures have specific record-keeping requirements that must be followed by project personnel.

Animals in Agricultural Settings

UCM and AAALAC International recognizes that the biomedical or agricultural research, testing or teaching objectives as well as the health and welfare of the animals will dictate when application of the recommendations of the Ag Guide, IL.AR Guide, or ETS 123 is most appropriate. For animals in an agricultural setting, AAALAC International takes the position that, …the housing and care for farm animals should meet the standards that prevail on a high-quality, well-managed farm. The collective professional judgment of the responsible oversight body (i.e., IACUC, Ethics Committee), principal investigator and veterinarian should determine which standard(s) applies best with regard to the care and welfare of agricultural animals, based on a performance approach in the context of the requirements of the study and the species used.* The rationale for making this determination should be documented.

Animal Incident Reporting

During the course of an IACUC approved research activity, an unanticipated or atypical event (including death of the animal) may occur. Such Animal Incidents are, by definition, occurrences that are not discussed in the Protocol covering the animal work. An unanticipated event is a serious event that impacts animal welfare and that may re-occur if no changes in procedures occur; examples would be unexpected complications from a surgical procedure, or injuries to animals during handling. An atypical event is generally a truly chance event that would not have been avoidable despite reasonable precautions; examples would be the loss of an animal due to an equipment failure or rare congenital condition.

If any Animal Incident occurs, personnel present at the event should immediately contact ARF personnel and/or the Attending Veterinarian if advice or assistance could reduce animal suffering or prevent a recurrence of the Incident. In all cases, an Animal Incident Report must be completed within 72 hours of the event and submitted electronically to the ARF Manager andIACUC Office. The Report describes the nature of the Incident and a Plan of Action to prevent recurrence, if appropriate. If a finalized Report cannot be submitted within 72 hours of the Incident, and initial Report should be submitted by this deadline with a follow-up Report submitted as soon as possible thereafter. The Report(s), including the Plan of Action, are reviewed by the Attending Veterinarian, ARF Director or designee, and the IACUC. Principal Investigators are reminded that any Plan of Action involving changes to procedures described in a Protocol will require an approved modification of the Protocol. Failure to report an initial

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Animal Incident Report within 72 hours may result in corrective action by the IACUC and/or ARF.

SEMIANNUAL REVIEWS AND POST-APPROVAL MONITORING

Twice each year the IACUC reviews the University of Central Missouri’s IACUC Policies and Procedures for animal care and use programs and inspects all UCM facilities where animals are housed and/or used. A subcommittee of the IACUC, composed of at least four members, to include the Chair and Attending Veterinarian shall conduct the semiannual reviews. No IACUC member wishing to participate in any review shall be excluded. The subcommittee may invite ad hoc consultants to assist in the reviews.

Types of Semiannual Review

Review of the IACUC Policies and ProceduresThe IACUC is required to semiannually evaluate the University of Central Missouri’s IACUC Policies and Procedures for animal care and use programs. This semiannual evaluation includes the following:

IACUC membership and functions, including protocol review practices IACUC records and reporting requirements Veterinary care, to include:

o Preventive medicine, animal procurement, and animal transportationo Surgeryo Pain, distress, analgesia, and anesthesiao Euthanasiao Drug storage and control

Personnel qualifications and training Occupational health and safety of personnel ARF Disaster Plan

The IACUC has developed specific semiannual audit forms and uses a Program and Facility Review Checklist as a guide when conducting its review.

Review and Inspection of Animal FacilitiesA semi-annual inspection of the Institution's animal facilities, using the 8th edition of the “Guide” as a basis for evaluation, will occur at least once every six months. The IACUC procedures for conducting semiannual facility inspections are as follows: Memos requesting each semiannual meeting include a request for committee members to conduct an inspection prior or during the IACUC meeting. The current inspection forms also accompany requests for meetings. Members are encouraged to contact animal care staff for tours prior to the meetings. No member who wishes to participate will be excluded from doing so. Any member who cannot attend the semiannual meeting will be encouraged to complete an inspection of the animal facilities via appointment with animal care staff. The semiannual facility inspection checklists found on the OLAW website: http://www.grants.nih.gov/grants/olaw/olaw.htm. are used as a guide along with the Guide for facility inspections.

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As part of its semiannual review, the IACUC will inspect all facilities where animals are kept longer than twelve hours and areas in which surgical manipulations are performed. Other areas, such as laboratories in which only routine injections, dosing, and weighing occur, will be monitored by random site visits and evaluations as necessary to ensure compliance. The IACUC maintains an updated list of all facilities to be inspected during its semiannual review. This semiannual review includes the following:

Animal housing and support areas Cage wash Aseptic surgery Transport Vehicles Procedure areas, non-survival surgeries, laboratories, and rodent surgeries

Semiannual Review Subcommittee and Reports

A semi-annual program review of the Institution's program for humane care and use of animals, using the 8th edition of the “Guide” as a basis for evaluation, will occur at least once every six months. The IACUC procedures for conducting semiannual program reviews are as follows: A detailed agenda is sent to each committee member prior to the review. All protocols are initially developed with input from a veterinarian. Electronic copies of protocols are submitted to the committee with electronic or hard copies distributed to committee members prior to the scheduled meeting for protocol reviews. A facilities review is conducted near the time of this meeting by the IACUC members. The semi-annual program review and facility review checklists and the Guide are based on sample checklists found on the OLAW website.

http://www.grants.nih.gov/grants/olaw/olaw.htm. (i.e. Policies and Responsibilities, Veterinary Medical Care, Animal Housing, Procedure Areas ... .Rodent Surgeries)

The IACUC procedures for developing reports and submitting them to the Institutional Official are as follows: After the facility inspection and protocol reviews have taken place the IACUC Liaison compiles a report to the Institutional Official detailing significant and minor deficiencies as well as recommendations and deadlines for correction. This report is reviewed and approved by the chair of the IACUC prior to being forwarded to the IACUC and Institutional Official. Deficiencies are summarized as suggested in the sample semiannual program and facility review from the OLAW website. The semi-annual report to the Institutional Official shall include a description of the nature and extent of the University of Central Missouri’s adherence to the “Guide for the Care and Use of Laboratory Animals” Any departures from the “Guide” will be identified specifically and the reasons for each departure will be stated and reported to the IO. Any minority views will be included with the report. The report will be signed by a majority of the IACUC members.

The IACUC shall submit the approved report to the Institutional Official and shall maintain a copy in its files. The report shall be made available to USDA, OLAW and any federal funding agencies upon request.

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Any failure to adhere to the plan and schedule identified in the report for correcting deficiencies that results in a significant deficiency remaining uncorrected, shall be reported in writing by the IACUC, through the Institutional Official, within 15 business days to APHIS. If the uncorrected deficiency is related to a federally funded activity, the relevant funding agency shall also be informed.

Monitoring of Corrective Action Plans

The IACUC shall provide a copy of the final semiannual report to the Research and Compliance Officer. The Research and Compliance Office shall monitor compliance with required corrective actions, as identified in the final semiannual report, and shall submit a written report to the IACUC. If any deficiencies are not remedied within the time period set forth in the final semiannual report, the IACUC shall take appropriate corrective action

Protocol Post-Approval Monitoring

Post-approval monitoring (PAM) of protocols is performed to provide assurance to regulatory agencies and to the IACUC that animal experiments are performed in accordance with approved protocols. The QA Monitor normally performs post-approval monitoring on behalf of the Research and Compliance Office and the IACUC. The QA Monitor confirms consistent and accurate performance of the IACUC-approved protocols, standard operating procedures and practices. The QA Monitor arranges and performs monitoring visits and procedure reviews, and oversees the continuous education for quality assurance in research at the University of Central Missouri. Post-approval monitoring may be performed as a “For Cause” investigation or routinely as a “Not for Cause” review.

The QA Monitor conducts “For Cause” Investigations at the request of the Research andCompliance Officer or the IACUC for a variety of reasons including:

Receipt of an internal complaint (i.e. Research Compliance Hotline, anonymous report) or internal concern of possible protocol violation or regulatory noncompliance

Receipt of an external complaint (the FDA, Sponsor, OLAW, or USDA) of potential protocol violation or regulatory noncompliance

Investigator history of poor adherence to UCM policies and procedures or regulatory requirements

The “Not for Cause” or routine post-approval monitoring may include:

Review of IACUC records and activities to ensure IACUC policies and procedures are consistent with regulatory requirements and federal assurances

Review of risk areas identified during periodic risk assessments of the Research and Compliance Program

Protocols randomly selected for on-site reviewIn post-approval monitoring:

All active and approved protocols and modifications are available for review

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All allegations of misuse, neglect or inappropriate protocol performance will be investigated

In general, the monitoring reviews will be scheduled with the Principal Investigator or other laboratory personnel in advance. Follow-up audits for the purpose of confirming Principal Investigator reported resolutions may be unscheduled

“For Cause” monitoring may be conducted at any time, with or without advance notice (i.e., unannounced) to the Principal Investigator

During each monitoring visit, the QA Monitor will compare procedures conducted in the laboratory with those listed in the approved protocol

The QA Monitor will provide a description of any discrepancies between the procedures performed in the lab and those listed in the protocol to the Principal Investigator

The QA Monitor will provide information to the IACUC by means of a written report. The report may include identification of:

o Unapproved personnel who are performing procedures in the protocolo Outdated cage cards, incorrect cage cards, or improperly labeled cage cardo Location of the procedure that does not match the location specified in the

protocolo Anesthetics/analgesics: unapproved regimen or route of administration, expired

date, improper useo Minor unapproved modifications to approved procedures that are performedo Other procedural deviations that can be corrected by submission of a minor

change requesto Incidents of animal distress that were not anticipated

The QA Monitor will discuss monitoring/auditing results with the Principal Investigator to confirm the observations for accuracy, and to assure a complete understanding of issues

The QA monitor shall refer issues that pose an immediate threat to animal welfare to the Research and Compliance Officer, the Attending Veterinarian, and the IACUC

The QA Monitor will send a final written report of the monitoring results to the Research and Compliance Officer, Principal Investigator, and the IACUC

As the QA Monitor determines necessary, he/she may recommend further training or retraining of personnel or modifications to procedures, and may perform a follow-up monitoring visit to check for compliance and to ensure the welfare of the animals and the integrity of the IACUC protocol process

REVIEW OF NONCOMPLIANCE

The IACUC investigates concerns involving the care and use of animals raised by complaints or reports of noncompliance received from the public or from research personnel or employees [9 CFR 2.31(c) (4)]. The University is required to report results of some investigations to OLAW, the USDA and/or AAALAC.

Identification of Compliance Issues

Anyone who has a concern or question about animal care and use at UCM, including protocol noncompliance or animal treatment, is expected to contact the IACUC Chair or the ARF

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Manager. The Attending Veterinarian, ARF staff and individual IACUC members must also report any suspected incidence of noncompliance. Strict confidentiality will be maintained to the extent possible and allowable by law. The University of Central Missouri prohibits retaliation against any employee who makes a good faith report of known or suspected noncompliance in the care and use of animals at UCM. Concerns include situations or activities in which animals are in immediate jeopardy and those in which violations of the Federal Animal Welfare Regulations or the Assurance are alleged but animals are not in apparent danger. They may also be past violations of the IACUC or ARF Policies and Procedures or protocol noncompliance.

INVESTIGATION OF ANIMAL CARE AND USE CONCERNS

Initial Evaluation and Actions

The Attending Veterinarian has authority to immediately halt activity on a protocol if he or she has reason to believe that animal welfare is being compromised. The Attending Veterinarian immediately notifies the affected Principal Investigator and the IACUC Chair in writing.

Upon receipt of a concern from any party, the IACUC Chair or his/her designee may convene an emergency meeting of the IACUC to determine whether the concern requires further investigation and immediate action, further investigation but no immediate action, or no action.Veterinary medical intervention, suspension of a research activity, and/or notification of appropriate safety, occupational health, or other officials, are examples of actions that may be taken immediately. Situations that involve potential criminal activity or human safety are reported promptly to UCM’s Public Safety or occupational health and safety officials. If immediate action is warranted to protect animal or human welfare, the IACUC notifies the Institutional Official or the Institutional Official’s designee(s). Any formal suspension of activity is reported to regulatory agencies.

Suspension of a Protocol

The IACUC may suspend activities on a protocol if it finds violations of the Institutional Policy, PHS Policy, the Assurance, or Animal Welfare Regulations. Suspension may occur only after review of the matter at a convened meeting of a quorum of the IACUC, and with the affirmative vote of a majority of the quorum present. If the IACUC suspends an activity involving animals, the Institutional Official in consultation with the IACUC shall review the reason for suspension.The Institutional Official or the Institutional Official’s designee(s) is required to take appropriate corrective action and report the action to regulatory agencies with full explanation.

Procedures for Reporting by the Institutional Compliance OfficialThe Institutional Compliance Official is responsible for reporting any unanticipated problems involving risks to subjects or others; any serious or continuing noncompliance with 45 CFR Part 36 or the requirements or determinations of the IACUC; and any suspension or termination of IACUC approval. The Institutional Compliance Official is responsible for reporting any such events to the following parties: the IACUC, the IO, the Provost and Vice President for Academic

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Affairs, the appropriate college dean, any agency or department which is funding the research; and OLAW. Such reporting will take place no more than five business days after a determination has been made that one of the events described above has occurred.

Actions by the IACUC in Response to Unanticipated ProblemsIn the event of unanticipated problems involving risks to the animals or others, the IACUC will evaluate the nature of the problems and decide on appropriate action, which could range from temporarily suspending the research project to terminating approval for the project and requiring the investigator(s) and appropriate institutional officials to resolve the problems.

IACUC Response to Serious or Continuing NoncomplianceGuidelines for the procedure for the investigation of allegations of scholarly or scientific misconduct are outlined in the Ethics in Research Document found in the UCM Faculty Guide. The IACUC may informally gather and process information to evaluate the nature of the IACUC problem for the purpose of determining if the criteria for an IACUC violation is met prior to reporting to the Ethics Committee (if the matter reaches those stages). In the event that serious or continuing noncompliance is determined, the IACUC will examine the record of noncompliance and take appropriate action.

Range of Possible Actions Appropriate action could range from requiring appropriate educational activities to recommending official reprimand of the investigator(s), listing the investigator(s) as ineligible to conduct research with animals at UCM, or recommending termination of employment.

PROGRAMMATIC DEFICIENCIES AND CORRECTIVE ACTIONS

The IACUC semiannual evaluations are tools for institutional self-identification and correction of facility and program deficiencies. Program deficiencies include:

Failure to correct situations identified as significant deficiencies in a timely manner Shortcomings in the programs of veterinary care, occupational health, training, or with

the IACUC Conditions that jeopardize the health or well-being of animals, including accidents,

natural disasters and mechanical failures resulting in actual harm or death to animals.

Programmatic deficiencies must be categorized as acceptable, minor, or significant. The corrective action for a significant deficiency must include a reasonable plan to correct the issues as well as a date by which the issue will be corrected. Significant programmatic deficiencies must be reported to the applicable regulatory agencies if the deficiency jeopardizes the health and welfare of the animals, or if UCM is unable to make the correction by the specified date.

The IACUC, through the Institutional Official or the Institutional Official’s designee, shall promptly report to OLAW, the USDA, and AAALAC, as appropriate, circumstances and actions taken with respect to:

Any serious or continuing noncompliance with PHS Policy Any serious deviation from the provisions of The Guide Any suspension of an activity by the IACUC

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In addition, the IACUC, through the Institutional Official or the Institutional Official’s designee, must report within 15 days any failure to correct a significant deficiency to the USDA and any federal agency funding the activity in which the significant deficiency was found.

Examples of reportable incidents include: Conditions that jeopardize the health or well-being of animals, including natural

disasters, accidents, and mechanical failures, resulting in actual harm or death to animals Conduct of animal-related activities without appropriate IACUC review and approval Failure to adhere to IACUC-approved protocols Implementation of any significant change to IACUC-approved protocols without prior

IACUC approval Conduct of animal-related activities beyond the expiration date established by the

IACUC Conduct of official IACUC business requiring a quorum in the absence of a quorum Conduct of official IACUC business during a period of time that the IACUC is

improperly constituted Failure to correct deficiencies identified during the semiannual evaluation in a timely

manner Chronic failure to provide space for animals in accordance with recommendations of The

Guide, unless the IACUC has approved a protocol-specific deviation from The Guide based on written scientific justification

Participation in animal-related activities by individuals who have not been determined by the IACUC to be appropriately qualified and trained

Failure to monitor animals post-procedurally as necessary to ensure well-being (e.g., during recovery from anesthesia or during recuperation from invasive or debilitating procedures)

Failure to maintain appropriate animal-related records (e.g., identification, medical, husbandry)

Failure to ensure death of animals after euthanasia procedures Failure of animal care and use personnel to carry out veterinary orders (e.g., treatments) IACUC suspension or other institutional intervention that results in the temporary or

permanent interruption of an activity due to noncompliance with the PHS Policy, Animal Welfare Act, The Guide, or UCM’s Animal Welfare Assurance

Agency-Specific Reporting Requirements

Office of Laboratory Animal Welfare (OLAW)The Institutional Animal Care and Use Committee (IACUC), through the Institutional Official or the Institutional Official’s designee(s), must contact the office of the Director of Compliance atOLAW immediately after:

Suspension of any activity by the IACUC A finding of serious or continuing noncompliance with the PHS Policy A finding of significant deviation from the provisions of the Guide

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After review of any allegation of non-compliance by the IACUC and the Institutional Official or the Institutional Official’s designee(s), a formal written report will be filed with OLAW within three months of the event stating a full explanation of circumstances, a description of corrective actions taken, any minority views filed by the IACUC, and the status of the research program.

United States Department of Agriculture (USDA)The IACUC, through the Institutional Official or the Institutional Official’s designee(s), must contact the Western Regional Director of Animal Care immediately in the following instances:

Suspension of any activity by the IACUC Failure to adhere to a plan to correct a significant deficiency

Federal Funding AgenciesThe IACUC, through the Institutional Official or the Institutional Official’s designee(s), must contact any Federal agency funding an activity involving the use of animals immediately in the following instances:

The activity is suspended by the IACUC The institution fails to adhere to a plan to correct a significant deficiency that affects the activity

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

Copies of all correspondence with OLAW and USDA regarding issues of noncompliance are forwarded to AAALAC in a timely manner

Non-reportable Incidents

Examples of incidents that are not normally required to be reported are: The death of animals that have reached the end of their natural life spans The death or failures of neonates to thrive when husbandry and veterinary medical

oversight of dams and litters was appropriate Animal death or illness from spontaneous disease when appropriate quarantine,

preventive medical, surveillance, diagnostic, and therapeutic procedures were in place and followed

Animal death or injuries related to manipulations that fall within parameters described in the IACUC-approved protocol

Infrequent incidents of drowning or near-drowning of rodents in cages when it is determined that the cause was water valves jammed with bedding (frequent problems of this nature, however, must be reported promptly along with corrective plans and schedules)

The Missouri Department of Conservation agents advise that regarding wildlife found injured in the field that is not a result of the research protocol:- They request that researchers do not interact or interfere with injured wildlife.- Only call authorities (appropriate county MDC agent or Sheriff) if species is listed as endangered.

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- They may or may not let the landowner know of presence of injured animal, however, MDC cautions that not all wildlife appearing injured are injured.- A dead/dying animal still maintains a role in the ecosystem and MDC would rather it be left alone unless listed as endangered.- MDC feels that, lacking significant data showing otherwise, a baited camera trap does not imply that an injured animal in the vicinity was attracted by the bait and wasn't simply there by chance.

REPORTING AND RECORDKEEPING

USDA Registration and Public Health Service Assurance The IACUC is responsible for completing the USDA Registration and PHS Assurance. The IACUC may seek input from the ARF Director, General Counsel and other individuals as necessary to complete these documents. The USDA Registration is renewed every three years. The PHS Assurance is renewed every five years. The USDA Registration and PHS Assurance are signed by the Institutional Official and submitted to the appropriate agency by the IACUC.

Annual Reports USDA/APHIS – The IACUC is required to submit an Annual Report to APHIS. The IACUC shall prepare the Annual Report for signature by the Institutional Official. The Annual Report shall outline UCM’s compliance with the AWA, the location of all facilities where animals are housed or used, and specific animal information as required by the AWA.The report shall cover the previous federal fiscal year, October 1–September 30. The IACUC shall submit the signed Annual Report to the Animal Care Regional Director for Nebraska on or before the first of December in each calendar year.

PHS/OLAW – At least once every 12 months the IACUC, through the Institutional Official, shall submit a written report, to include any minority views, to OLAW. The report shall include the following:

Changes to UCM’s program or facilities that would place it in a different category than specified in our Assurance;

Changes in the IACUC membership; Changes in the description of UCM’s IACUC Policies and Procedures for animal care

and use programs as outlined in the Assurance; Dates that the IACUC conducted its semiannual evaluations and submitted its reports to

the Institutional Official.

If there are no changes, the report shall state that there are no changes and shall inform OLAW of the dates of the semiannual evaluations and submission of semiannual reports to the Institutional Official.

Semiannual Reports

Upon completion of semiannual reviews he IACUC shall submit written semiannual reports to the Institutional Official.

Record Keeping Requirements

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The IACUC shall maintain Applications and Continuing Review forms submitted for review; minutes of meetings, including records of attendance; activities of the IACUC and deliberations, records of proposed activities, and proposed significant changes, including whether the IACUC approval was given or withheld; records of semiannual reports and recommendations; andUCM’s Assurance, USDA Registration and annual reports to government agencies. These records shall be retained as follows:

Five-Year Retention – The IACUC shall retain the Assurance for at least five years or until such time as a new Assurance is approved, whichever is longer.

Three-Year Retention – The IACUC shall retain the following records for at least three years:

o Records of semiannual IACUC reports and recommendations,o Records of animals,o Records of any accrediting body determinations, if applicable,o Annual reports,o USDA Registration.

Other – The IACUC shall retain records relating to proposed activities and significant changes in ongoing activities reviewed and approved by the IACUC for the duration of the activity and three years after the end of the activity. Such records include, but are not limited to, records of Applications, Continuing Review forms, minutes of IACUC meetings, and records of investigations of noncompliance related to an approved protocol.

Animal Resource Facility Disaster Plan

The IACUC is ensuring that the Animal Resource Facility maintains an effective plan to respond to crisis events (Disaster Plan). The UCM ARF Disaster Plan is currently under development and will contain procedures to be followed in event of equipment (HVAC, electrical, plumbing) failures, natural disasters, disease outbreak, and animal rights activity (anticipated completion of the plan - July 2013). The Animal Resources Facility Disaster Plan will be reviewed as part of the IACUC Semiannual Program Review.

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