Welcome to the Essentials for IACUC Members web course! This course is part of an instructional instructional series funded by the Department of Veterans Affairs Office of Research and Development through the Medical Research Service. It is designed primarily for IACUC members and IACUC support administrators.

This course addresses many topics that are based upon regulatory language which is itself subject to interpretation. We have gone to great lengths to differentiate fact from opinion throughout, but if we have failed or have made an error, please bring it to our attention immediately by clicking on the Submit Comment link at the top right when you are on the "offending" page.

If you haven’t already done so, you may wish to complete the Working with the VA IACUC or Working with the IACUC web course before beginning this course. The lessons in this course build upon the lessons presented in those courses.

To see a complete list of support, authoring, reviewing, and graphics credits for this course, click here.

Click on the “Next” button above the text to go to the next screen.

As in the Working with the IACUC web course, use the arrows above to move through the pages in the lessons.

To jump to the start of any lesson at any time, click on any of the Lesson Topics listed to the left. You can use the scroll bar to the right of the lesson menu to see all the lessons available. You can also use the scroll bar to the right of this text box to see any text not showing at the bottom.

The underlined blue links at the top of this text area do the following when clicked:

Research Training Home Page: Opens a new window and loads the ResearchTraining home page.

Courses and Exams: Takes you back to the page where the available courses and exams are shown.

Submit Comment: If you have a comment or notice an error on a page, this will let you leave a message for the course authors.

Log Off: Takes you completely out of the ResearchTraining site.

At the end of most lessons, you will see self-assessment questions to help you retain the information presented. These questions make up the question pool from which the self-assessment exam is constructed. You will get feedback on your answers, but your responses to the questions while in this course are not recorded or tallied. You must take and pass the exam for this course to get credit for it.

The exam has 20 or more questions, and the pass point is around 85%. You may take the exam as many times as you wish. The questions are randomized, so each exam is different. Once you pass, you will be able to print a certificate of completion for this course as an option.

The software tracks your progress between sessions by placing a maroon dot next to lessons you complete. When you finish this lesson, look for the maroon dot next to Lesson #1 on the lesson menu at left. You will be able to see which lessons you have completed by noting the location of the dots. Most people will want to do the lessons in order because many of the lessons build on material in previous lessons, but you may skip around as you wish.

Lesson tracking will not be affected if you have an Internet problem and or you get disconnected from the course before finishing. Just be sure to log into the ResearchTraining website using the same username/password combination each time.

Before starting the course, a quick comment about the issue of USDA (U.S. Department of Agriculture) and PHS (Public Health Service) jurisdiction. Although some institutions are not subject to the USDA Animal Welfare Act Regulations and some are not subject to PHS Policy, this course has been written with the assumption that your institution seeks to meet the regulatory requirements of both of them.

There are some differences in the way the USDA Animal Welfare Act Regulations and PHS Policy handle some animal research issues, mainly because the USDA Animal Welfare Act Regulations currently do not apply to most research mice and rats. However, it is a best practice to conduct IACUC business in a way that complies with both USDA Animal Welfare Act Regulations and PHS Policy no matter what species is involved, and no matter what source of funds is used to fund the research. This practice helps to ensure uniform and consistent standards, an essential ingredient of an animal care and use program. It will also demonstrate to the public that regardless of the funding source, care and use standards are the same for all animals.

Remember that the Animal Care Section of the Animal and Plant Health Inspection Service is the entity at USDA that enforces the Animal Welfare Act public law through the Animal Welfare Act Regulations.

The Office for Laboratory Animal Welfare (OLAW, formerly OPRR) is the entity at PHS responsible for enforcing the Health Research Extension Act public law through PHS Policy. PHS Policy consists of:

- A primary document, PHS Policy for Humane Care and Use of Laboratory Animals, which incorporates the U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training as a framework for the conduct of animal research; and

- A second document, the Guide for the Care and Use of Laboratory Animals (known simply as the Guide), which is incorporated into the first document by reference. The Guide addresses institutional policies and responsibilities related to animal husbandry, the housing and caging environment, veterinary care, and many aspects of the physical plant (surfaces, heating, ventilation, and air conditioning).

The regulatory documents used by USDA and PHS can be grouped into three categories- public law, regulations, and interpretive rules (guidance). Because institutions must comply with all of them, a discussion of these categories is not relevant to most IACUC members. However, if you would like to learn more about these categories of documents and how they relate to each other, click here.

The goals of this course are as follows:

1. To provide IACUC members with information essential to performing their jobs on the IACUC, including interactions with institutional administrators as well as regulatory and accrediting agencies.

2. To help meet mandatory training requirements in the USDA Animal Welfare Act Regulations and PHS Policy.

3. To offer best practices that can help IACUCs maintain a high level of performance and compliance in institutional animal care and use programs.

The Institutional Animal Care and Use Committee, or IACUC, is a critical component of a quality program of animal care and use in a research, teaching, or testing environment. The basic role and responsibilities of the IACUC will be covered in this course. Here’s a quick list of the most important ones:

1. Review and approve proposed activities involving animals in research, testing, or teaching, and significant changes to previously approved activities.

2. Evaluate the animal care and use program and the animal facility itself at least every six months.

3. Review any concerns about the care and use of animals at the institution.

4. Suspend previously approved animal work if its conduct is not in compliance with regulations or consistent with conditions of approval.

5. Report to a designated “Institutional Official” to make sure the institution is aware of issues affecting the animal research program.

What about the responsibilities of individual members? General responsibilities include:

1. Attend as many meetings as possible so that business can be conducted efficiently and continuity is maintained.

2. Come prepared to discuss animal protocols on the agenda.

3. Understand what issues must be considered when reviewing animal protocols (the Working with the IACUC web course will help you with this).

4. Attend the semi-annual self-review of the animal care and use program and inspection of the animal facilities, and

5. Participate in discussions. Very important- Members should not be afraid to ask questions or offer contrasting opinions.

A free and open discussion is a key to effective IACUC reviews.

Non-affiliated and non-scientific members should not be intimidated by scientific jargon. Their perspective is critical and their observations can raise important issues that have been overlooked or not otherwise considered.

The U.S. Congress does not intend to force an institution to disclose trade secrets or commercial or financial information of a privileged or confidential nature when complying with PHS Policy.

Furthermore, Congress expects that confidential information obtained by IACUC members as part of their duties remain confidential. The Animal Welfare Act states that it is against the law for an IACUC member to disclose confidential information such as trade secrets, operations, or the identity, confidential statistical data, amount or source of any income, profits, losses, or expenditures, of the research facility.

The Animal Welfare Act allows fines for IACUC members who violate confidentiality regulations. However, this provision of the Animal Welfare Act is not intended to discourage participation on the IACUC, but rather to protect institutions from malicious conduct. And the USDA Animal Welfare Act Regulations (which implement the Animal Welfare Act itself) state that reports of violations to regulatory agencies by IACUC members are not violations of confidentiality rules.

The USDA Animal Welfare Act Regulations, which enforce the Animal Welfare Act itself, clearly provide protection against discrimination or reprisals for whistleblowers who report violations of the Animal Welfare Act or Animal Welfare Act Regulations to regulatory agencies. IACUC members who report violations to regulatory agencies are also covered, and such reporting is not a violation of confidentiality rules.

The USDA Animal Welfare Act Regulations state that:

No facility employee, Committee member, or laboratory personnel shall be discriminated against or be subject to any reprisal for reporting violations of any regulation or standards under the Act;…

IACUC members must be sensitive of even the perception of a conflict of interest. The USDA Animal Welfare Act Regulations state the following:

No member may participate in the IACUC review or approval of an activity in which that member has a conflicting interest (e.g., is personally involved in the activity), except to provide information requested by the IACUC…

PHS Policy includes similar language about conflicts of interest. Policy #15 in the USDA/APHIS Policy Manual also states that no member may vote on his/her own proposal.

It is a best practice to make sure that members with conflicts remove themselves completely from the meeting room for the duration of deliberation, and that the IACUC minutes note which members do so. This protects both the "conflicted" member and the IACUC from any appearance of impropriety. Conflicted members do not contribute to a quorum (quorums will be discussed in a later lesson).

As a practical matter, and if consistent with local IACUC policy, members with conflicts may summarize their protocols as a courtesy to other IACUC members when they come before the committee. But conflicted members should recuse themselves from the room before honest and open IACUC deliberations begin.

PHS Policy and the USDA Animal Welfare Act Regulations both require that members with certain backgrounds and skills serve on an IACUC. Only an IACUC that has all the required members appointed is considered to be a constituted IACUC. Only a constituted IACUC can conduct official business.

There is much overlap between the USDA Animal Welfare Act Regulations and PHS Policy regarding IACUC membership. To comply with both of them in constituting an IACUC, the following members must be appointed:

1. A Chairperson.

2. A veterinarian with program responsibility and authority in the animal research program.

3. A practicing scientist experienced in research involving animals.

4. A member whose primary concerns are in a nonscientific area.

5. A member who is not affiliated with the institution in any way other than as a member of the IACUC. This person also cannot be a member of the immediate family of a person who is affiliated with the institution.

The first required member of the IACUC is the Chairperson. There are no skill or credential guidelines for the Chairperson mentioned in PHS Policy or USDA Animal Welfare Act Regulations. However, as the leader of the IACUC, it is a best practice for the chairperson to have certain life skills and experiences:

1. Experience or familiarity with animal research and animal research regulations.

2. A working knowledge of parliamentary process to conduct IACUC business fairly and efficiently.

3. Enough maturity to keep deliberations focused, to make sure all IACUC members can participate, and to prevent attempts to silence dissenting opinions.

4. Some institutional authority in order to perform duties without concern that IACUC actions may jeopardize position or career.

The second required member of the IACUC is a veterinarian. But not just any veterinarian- the veterinarian with authority in the animal care and use program who serves on the IACUC is officially termed the "Attending Veterinarian" by USDA (and sometimes the "Institutional Veterinarian" by OLAW).

The attending veterinarian is the only member who serves on the IACUC on the basis of position of employment. The Attending Veterinarian's permanent position on the IACUC is described by the Latin term "ex officio", meaning "by virtue of the office." A common misconception is that ex officio means non-voting, but this is not correct.

Other veterinarians working at an institution may also serve on the IACUC, but they cannot replace the attending veterinarian on the IACUC.

The attending veterinarian must meet the following criteria:

1. They must have graduated from a veterinary school accredited by the American Veterinary Medical Association's Council on Education, or have a certificate issued by the American Veterinary Medical Association's Education Commission for Foreign Veterinary Graduates, or have received equivalent formal education as determined by the USDA (Chief) Administrator.

2. They must be certified by the American College of Laboratory Animal Medicine (ACLAM) or have received training and/or have experience in laboratory animal medicine and in the care and management of the species at the institution.

3. They must have direct or delegated authority (and accordingly, responsibility) for activities involving animals at the institution.

More detailed information on the components of a good veterinary care program are available in a report published in 1996 by the American College of Laboratory Animal Medicine. To see the report, click here.

The Attending Veterinarian is given additional authority and responsibilities by USDA that integrate with IACUC functions:

The Attending Veterinarian (AV) or a designee must approve specific details of proposals involving surgery, including pre- through post-procedural care and relief of pain and distress, and to change postoperative care as necessary to ensure the comfort of animals.

2. The AV must make recommendations regarding activity level or restrictions of animals in health records.

3. The AV must decide when necropsies (autopsies) of animals should be performed to investigate health problems in the institution.

4. The AV or a designee must provide consultations during the planning stages of proposed animal activities that involve more than momentary pain or distress. (Informal discussions with USDA suggest that this consultation is expected to occur before the IACUC meeting).

5. When dogs must be exercised, the attending veterinarian must determine the frequency, method, and duration of dog exercise in consultation with and approval by the IACUC.

6. The AV must direct the required environmental enrichment plan for primates.

As in each of the preceding responsibilities of the attending veterinarian, the overall veterinary care program is carried out with the approval of the IACUC. It is important, therefore, for the attending veterinarian and IACUC to work together closely and well.

The third required member of the IACUC is a practicing scientist. The member of the IACUC that fulfills the required role of the scientist must have experience in research involving animals. Further guidance is not given, but it is always helpful to have a scientist on the IACUC with expertise and knowledge that overlaps with the research being proposed to the IACUC. Often, the majority of IACUC members at larger institutions are scientists with animal research experience.

The fourth required member of the IACUC is the non-scientific member ("NSM"; sometimes termed the "lay" member). This member must be an individual whose primary concerns are in a nonscientific area (for example, an ethicist, lawyer, or member of the clergy).

It is common sense and a best practice for the Chair and other IACUC members to make sure that this member has an adequate understanding of review issues before the IACUC. Accordingly, the use of jargon should be minimized whenever possible, and questions raised by any member during the meeting should be addressed to the satisfaction of the non-scientific member (as well as the non-affiliated member discussed below).

The fifth and final required IACUC member is the non-affiliated member. The non-affiliated member (or "NAM") must meet the following criteria:

1. Must not be affiliated in any way with the institution other than as an IACUC member.

2. Must not be a member of the immediate family of a person who is affiliated with the institution.

3. Must be a person who does not utilize laboratory animals.

As just discussed for the non-scientific member, it is common sense and a best practice for the Chair and other IACUC members to make sure the non-affiliated member has an adequate understanding of review issues before the IACUC.

The intent of having the non-affiliated member on the IACUC is to provide representation for general community interests in the proper care and treatment of animals. The Guide adds the condition that this member may not be involved in the use of laboratory animals.

Both PHS and USDA allow financial compensation to the non-affiliated member for expenses such as travel, parking, meals, and even participation, as long as such compensation:

1. Is not so substantial as to be considered an important source of income.

2. Does not influence the member's voting on the IACUC, or

3. Does not qualify the member as an employee of the institution.

Members of the clergy, teachers, and lawyers are often sought to fill this position on the IACUC. USDA Policy #15 specifically allows a veterinarian to fulfill this role as long as the veterinarian is not the Attending Veterinarian.

Although allowed by PHS Policy, having one member fulfill more than one required role is discouraged by both PHS and USDA. Of all the possibilities for members fulfilling more than one required role, members serving as both the non-scientific member and non-affiliated member are probably the most common today.

The five required members of the IACUC have now been described. There are a few more points to consider.

1. The required members must be voting members. This is implied by language in many places in the Animal Welfare Act Regulations and PHS Policy.

2. Consultants may be used to provide expert guidance to the IACUC, but may not approve or withhold approval of an activity or vote with the IACUC unless they are also members of the IACUC.

3. The USDA Animal Welfare Act Regulations stipulate that no more than three members may come from the same administrative unit of the facility. In a typical institutional setting, this may be implemented at the departmental level such that no more than three members of the IACUC come from one department.

As already discussed, it is a legal requirement that an IACUC have the proper types of members and thus be constituted. However, there is no legal requirement that every IACUC member attend every meeting, nor is any certain member required to be present to conduct business.

This can be confusing to research administrators because the committee responsible for reviewing human research proposals (the IRB, or Institutional Review Board) cannot conduct business unless at least one non-scientific member is present. No equivalent regulatory requirement exists for the IACUC at this time.

The IACUC must meet at least twice a year to approve the semi-annual evaluation (covered in three lessons later on), but IACUCs at larger institutions often meet once a month, and sometimes even more often. To help members plan to attend meetings, it is a best practice to schedule IACUC meetings far in advance, and to announce the dates to all research staff. This allows IACUC meetings to be scheduled to avoid holidays and attendance at professional meetings that could otherwise reduce attendance, and allows investigators to plan their protocol submissions.

Ultimately, it is the institution itself that is responsible for the animal care and use program. However, the IACUC's role is critically important- on behalf of the institution, it serves as the self-regulatory body immediately responsible for institutional animal research activities.

To meet its regulatory mandates, the IACUC must interact effectively with two administrators given specific responsibilities by the Animal Welfare Act Regulations and PHS Policy:

1. The CEO (Chief Executive Officer)

2. The IO (Institutional Official)

The CEO is characterized as the highest operating official of the institution (such as the president of a university). The CEO is required to appoint members qualified to serve on the IACUC, although the CEO may delegate this responsibility in writing.

The IO, or "Institutional Official" is the person in the organization having the administrative and operational authority to commit institutional resources to ensure that the animal care and use program complies with requirements of the Animal Welfare Act Regulations and PHS Policy.

In some institutions, the IO and the CEO may be one and the same, whereas in other institutions, particularly large ones, the CEO may be further removed from the day-to-day program oversight and may appoint someone else to be the IO.

Earlier in this lesson, it was stated that the CEO is required to appoint IACUC members unless that responsibility is given to the Institutional Official (IO) in writing. What is the role of the IO in the animal care and use program?

Both the Animal Welfare Act Regulations and PHS Policy define the IO as the individual at a research facility who is authorized to legally commit resources on behalf of the research facility to comply with applicable regulations. The next screen identifies the responsibilities of the IO.

The duties of an IO will be covered in more detail and from an IACUC perspective later in this course. The following is a brief list of the responsibilities assigned to the IO:

1. The IACUC must notify the IO whenever significant deficiencies are found in the animal care and use program.

2. When progress toward correcting significant deficiencies falls short of the plan and schedule for these corrections, the IACUC must inform the IO.

3. When the IACUC suspends a protocol previously approved by the IACUC, the IO, in consultation with the IACUC, must review the reasons for the suspension and take appropriate corrective action, and report the incident to OLAW, the USDA/APHIS, and other affected federal funding agencies.

4. The IO must receive recommendations from the IACUC about any aspect of the animal care and use program, facilities, or personnel training.

5. The IO must sign the PHS Assurance document which must be submitted and approved by OLAW prior to use of PHS funds for animal research (more on this later).

6. The IO must sign the USDA/APHIS Annual Report which must be submitted annually to the USDA (more on this later).

Additionally, OLAW has urged institutions to adopt the following as best practices:

1. The institutional or attending veterinarian and the IACUC should report directly to the IO.

2. IO should clearly define and assign responsibilities and reporting channels for other essential program elements such as training, occupational health, and facility maintenance.

The USDA Animal Welfare Act Regulations and PHS Policy provide the IACUC with authority to approve animal studies on behalf of the institution. The IO or any other administrator may suspend any animal study for any reason without IACUC concurrence, but these officials do not have the authority to approve an animal study in the absence of IACUC approval.

For example, a research chief or medical school dean could suspend an animal protocol already approved by the IACUC, but he/she could not allow use of animals prior to approval by the IACUC.

What authority does the IACUC really have? To begin with, the USDA Animal Welfare Act and PHS Policy grant the IACUC authority as the approving body for granting approval to use animals in research, teaching or testing.

Very important- Other committees and institutional officials are not allowed to approve such activities involving animals in the absence of IACUC approval.

Although not technically addressed by the USDA Animal Welfare Act regulations or PHS Policy, common sense dictates that only the IACUC can grant approval to restart activities it previously suspended.

The USDA Animal Welfare Act Regulations and PHS Policy also give the IACUC authority to suspend any activity previously approved.

What if the IACUC determines that an activity is occurring that has not been approved? Does it have the authority to suspend the activity? The answer is yes. Although not specifically addressed by the USDA Animal Welfare Act Regulations or PHS Policy, OLAW and USDA have stated that this authority is implied.

It is important to remember that an institution can give any number of officials the right to suspend animal use activities, without IACUC agreement. Examples of reasons for non-IACUC institutional suspensions include lack of funds and changing research priorities.

However, the IACUC must follow a formal process for suspending activities. This process is described on the next page.

Very, very important! For an IACUC to suspend an activity, it must take the following three steps:

1. Convene a meeting of a quorum (more than 50%) of voting IACUC members and review the activity to determine if it is being conducted in accordance with the description of the activity approved by the IACUC, and in accordance with the Animal Welfare Act Regulations and PHS Policy.

2. Vote to suspend the activity by a majority vote of the quorum present at the meeting.

3. Notify the IO that the IACUC has voted to suspend a protocol.

The IO must, in consultation with the IACUC, review the reasons for suspension, take appropriate corrective action, and report that action with a full explanation to USDA (Animal Care), PHS (OLAW), and any other federal agency funding that activity.

Thus, the steps necessary for an IACUC suspension of an activity are well defined. Remember that an institution may give any administrative official (including the IACUC Chairperson) the authority to suspend an activity, but such a suspension would not be an IACUC suspension.

What happens if an IACUC member finds out that a project is being performed without IACUC approval, or that work underway goes beyond what is approved by the IACUC?

It might take days to convene a quorum of the IACUC and review the facts, and sometimes such delay might put additional animals at risk. This is when the IACUC Chair and IO should immediately get involved to decide if immediate action by the IO is warranted until the IACUC can review the facts and decide if a suspension is warranted.

Remember, neither the USDA Animal Welfare Act Regulations nor PHS Policy give any IACUC member the authority to suspend an activity outside of the process covered in the previous page! However, such authority may be given to IACUC members by the institution, and in exceptional circumstances, common sense may dictate that a member of the IACUC should act immediately to stop a procedure or activity.

Remember - After voting to suspend an activity it has previously approved, the IACUC must then notify the IO. The IO must then notify USDA, PHS, and any other federal agency that provided funds for the suspended project.

As a best practice, the letter reporting a suspension should provide specific details as follows:

1. How and when the IACUC became aware of the problem.

2. What the IACUC did to investigate the problem.

3. What the IACUC found.

4. The date of the convened meeting in which a majority of a quorum of voting members suspended the project.

5. What the institution did to correct the immediate problem.

6. What the institution is doing to prevent further problems of this type.

How soon should USDA and PHS be notified that a project has been suspended? There is no specific guidance in the Animal Welfare Act Regulations or PHS Policy, but simply put, the sooner the better.

It is a best practice to notify both agencies by phone as soon as an activity is suspended to let them know that the IACUC has acted in a manner consistent with self-regulation, and that correspondence will be forthcoming.

It is also a best practice to make sure USDA and PHS hear about suspensions from you before someone else tells them. Timely and complete disclosure is important to maintaining public trust in the research endeavor. This prevents the appearance of a coverup and averts reporting by a whistleblower to groups outside of the institution.

Remember that AAALAC (Association for Assessment and Accreditation of Laboratory Animal Care, International) requires accredited institutions to promptly notify AAALAC of adverse events relating to the animal care and use program. Examples include investigations by the USDA or OLAW, IACUC suspensions of projects, and other serious incidents that negatively impact animal well-being.

What is a suspension? OLAW has defined an IACUC suspension as "an IACUC intervention that results in the temporary or permanent interruption of an activity involving animals." Thus, even a temporary hold on a project is considered by OLAW to be a suspension, and should be reported.

It is a best practice to make sure USDA, PHS, and AAALAC hear about suspensions from you instead of from someone else. Timely and complete disclosure is important to maintaining public trust in the research endeavor, and in the IACUC’s critical role in responsible self-regulation.

For the IACUC to conduct any formal business, a quorum of members must be present. Both the USDA and the PHS stipulate that for the purpose of IACUC business, a quorum means a majority of the voting members, i.e., greater than 50% of the voting members.

A common mistake is for an IACUC to start out with a quorum then continue to conduct business after the quorum is lost. This can happen after voting members leave the meeting early or when voting members recuse themselves from deliberations due to conflicts of interest. A quorum must be present each time an issue is before the committee. If a quorum is temporarily lost due to a member recusing himself/herself due to a conflict of interest, no offical action on that item may be taken.

What can IACUCs do to help make sure that a quorum is maintained at all times?

First and foremost, all members must understand the importance of attending all meetings. Accordingly, it is a best practice for the CEO or IO to periodically attend meetings to make sure that the IACUC members understand that their work on the committee is both important and valued.

Second, administrators should consider providing a meal or snack to IACUC members during the meeting. This helps morale and also helps maintains energy and concentration when meetings go overtime.

Although IACUC members should be expected to attend all meetings, busy schedules can result in absences at IACUC meetings.

One way to help maintain a quorum is to make sure the IACUC has an odd number of voting members. For instance, if an IACUC has 6 members, 4 must be present to conduct any business. If another voting member is added to bring the total to 7, only 4 voting members must still attend. Having that extra "odd" voting member provides another opportunity to reach a quorum without increasing the quorum requirement.

Some institutions appoint alternate IACUC members that attend a meeting when the primary member cannot attend. This has the benefit of increasing the likelihood that a quorum will be available. There is no mention of using alternate members in the USDA Animal Welfare Act Regulations or PHS Policy, but OLAW and USDA have offered some guidelines on the use of alternate members to ensure that the use of alternates is in accordance with PHS Policy and USDA Animal Welfare Act Regulations (see next page).

This OLAW/USDA guidance states that alternates must:

-Be appointed by the CEO (or the delegated official) and listed in IACUC rosters submitted with regulatory documents.

-Receive all proposal materials in advance of the meeting for review if they will be voting during the meeting.

-Be designated to serve as the alternate for a specific member, and receive training. A person may not be designated an alternate IACUC member shortly before or during a meeting as a convenience to achieve a quorum, and a pool of alternates may not be used.

-Meet the service requirements for the member being replaced. For instance, an alternate for the non-affiliated member must also meet the requirements to serve as a non-affiliated member.

-"Vote their conscience" as opposed to representing the position of the regular member for whom they serve.

If both the primary and alternate attend a meeting, only the primary may vote.

Remember that there must be a one-to-one link between a regular member and an alternate- an alternate for one member cannot be used on short notice to substitute for another voting member. However, the USDA and OLAW have recently clarified this position. Alternate member X may be specifically designated as an alternate for more than one regular member so long as the linkages are clear and specific, all other requirements are met, and provided that one alternate cannot simultaneously fill in for more than one regular member. For instance, an alternate scientific member may not serve as a generic alternate for all regular scientific members. However he may be designated an alternate for scientific member A and as an alternate for scientific member B provided he fills only one position in the absence of both A and B. Moreover, alternate member X and alternate member Y may both be designated as a replacement for regular member A, but only one may replace A on any given occasion. For more information refer to: Reference Document

OLAW does not permit solicitation of IACUC member votes through polling in lieu of a convened meeting of the IACUC.

OLAW describes polling as sequential, one-on-one communication, either in person or via telephone, e-mail, fax, U.S. mail, or by other similar means. The key concept is that a convened meeting requires interaction of a quorum in real time.

According to OLAW, “the quorum of IACUC members must be in direct communication with each other and be given full opportunity to participate for the duration of the meeting.”

It is this process of joint deliberation that is the intent of the Animal Welfare Act and the PHS Policy in requiring IACUC review.

Because polling does not allow direct communication between all members of the IACUC, OLAW does not allow polling of IACUC members to substitute for a convened meeting, nor does OLAW allow polling as a means of suspending an approved activity. (Remember that the IACUC can only suspend a previously approved activity at a convened meeting).

When is polling appropriate?

Polling is an appropriate mechanism for providing all committee members with the opportunity to call for full review of a protocol prior to initiating the designated reviewer method of protocol review (we will discuss protocol reviews in more detail later). It may also be appropriate as a mechanism for distributing and reviewing drafts of meeting minutes or reports.

With the advent of telecommuting, telephone conferencing, videoconferencing, and even interactive Internet "chat rooms", many IACUCs are considering new ways of convening their meetings. OLAW considers face to face meetings to be the preferred method of conducting meetings, and has provided the following guidance:

"To be considered a valid IACUC meeting, all members must be given ample prior notice to participate, and at least a quorum of the voting members must be convened on the same conferencing (telephone or audio-visual) line. In addition, the quorum of IACUC members must be in direct communication with each other and be given full opportunity to participate for the duration of the meeting. In either case, minutes of the meetings must be compiled and maintained on file as required by oversight and regulatory agencies."

At the present time, methods of telephone and video conferencing may be acceptable in exceptional circumstances. If your IACUC has a need to utilize telephone or video conferencing as a routine practice, it should contact OLAW and USDA for the latest guidance.

One of the most important IACUC activities is the review of animal proposals for research, testing, or teaching. Although not technically a regulatory requirement, virtually all institutions provide prepared forms for their investigators to use to guide them in providing adequate information for the IACUC review. From this point on, the term “protocol” will be used to describe the forms prepared by investigators and submitted to the IACUC for review.

Two resources to help IACUCs with protocol reviews are a sample protocol form on the OLAW web site, and IACUC review resources on the USDA Animal Welfare Information Center web site.

Many IACUCs assign personnel to conduct a pre-review of animal protocol forms before IACUC members review the forms. Pre-reviews can be limited to administrative issues such as documentation of training or enrollment in the occupational health and safety plan, or they can involve a veterinarian or other IACUC members and consist of a full review. Although pre-reviews require work, they often dramatically increase the efficiency of IACUC reviews. This is because the pre-review results in fewer corrections and clarifications for the IACUC to document during the actual meeting, and less delay for investigators. For instance, a pre-review may reveal that a protocol is missing information that would delay IACUC approval if not discovered until the time of review- drug doses, complete description of procedures, etc.

But remember, the Animal Welfare Act Regulations state the following:

"Procedures that may cause more than momentary or slight pain or distress to the animals will...involve, in their planning, consultation with the attending veterinarian or his or her designee."

To ensure compliance with the law and to increase IACUC efficiency, it is a best practice to conduct a pre-review of all protocols, and to involve a veterinarian in the pre-review.

After the pre-review stage, the review process begins. The first step in the IACUC’s review process is to receive a list and description of protocols (and any proposed activities) to be reviewed.

Both the Animal Welfare Act Regulations and PHS Policy stipulate that prior to IACUC review:

-Each member of the IACUC must be provided a list of proposed activities to be reviewed;

-Written descriptions of all proposed activities that involve the care and use of animals must be available to all IACUC members.

A best practice is to avoid a literal interpretation that only a list of protocol names need be provided to IACUC members before the meeting unless they request the protocol documents themselves. IACUCs routinely provide the actual protocols as well as an agenda listing the protocols scheduled for review. This is generally considered necessary to adequately prepare IACUC members to deliberate on these activities at the meeting.

In addition to providing the animal protocols to the IACUC members for review prior to the meeting, it is a best practice to also provide grant applications or other scientific documents to the IACUC members that help explain the overall research strategy and put the animal studies in context.

Many institutions that provide supplemental grant documents to facilitate IACUC reviews do not provide such materials to all IACUC members. Rather, they do so only to IACUC members who serve as primary and secondary reviewers to lead discussions on each protocol before the full committee. This reduces the copying burden and paper usage.

Once the IACUC members have the protocols in advance of the meeting, there are only two protocol review methods recognized by USDA and PHS for review and approval of animal activities:

-Full committee review (review during a convened meeting.)

-Designated review.

Deviations from compliance often arise when these review methods are either hybridized or altered substantially.

*** Full Committee Review ***

In the first method, full committee review, the IACUC members meet to review and deliberate on the proposed animal research protocols. To officially review any proposal, a majority of voting members (a quorum) must be available to vote on each proposal after any members with conflicts of interest recuse themselves from the meeting room. Official action can then be taken on each protocol.

Remember: Members who recuse themselves for conflicts of interest do not count toward the quorum. If the quorum is lost due to recusal, then the activity cannot be voted upon- rather, the vote on the activity must be tabled until a future meeting with a proper quorum.

*** Designated Review ***

The second method, the designated review or "DR" system, is a little more complex. This is how it must work to satisfy minimum regulatory requirements:

1. IACUC members are sent a list of protocols to be reviewed by the IACUC.

2. If no IACUC member decides that a protocol needs review by the entire IACUC, then that protocol becomes eligible for designated review. However, any member may request a full committee review of any protocol (full committee review was discussed on the previous page).

3. Any protocols eligible for designated review are assigned by the Chairperson to one or more qualified voting members of the IACUC, who can then review and decide what further action is necessary on behalf of the IACUC. Designated reviewers have three options: approve, require modification in (to secure approval), or request full committee review. Designated reviewers are not allowed to withhold approval. More on review options will be discussed in Lesson 8.

In summary, the designated review system allows the IACUC to designate one or more individuals to act on its behalf if no IACUC member requests a full committee review.

If more than one designated reviewer is utilized, what happens if they cannot agree on the review outcome? For instance, if one designated reviewer decides that full committee review is needed, and two others disagree, what happens? Because any voting member of the IACUC can request full committee review, full committee would be required in this case.

Even if disagreements between reviewers are not as dramatic, OLAW has stated that designated reviewers must agree, or full committee review is required. Designated reviewers do not vote, and majority-based voting by designated reviewers to decide upon an outcome is not allowed (click on link above for documentation).

Very useful examples of compliant and non-compliant review systems are provided by OLAW in a recent publication.

It can be very difficult for the IACUC members to determine whether or not a protocol should be given full committee review when only a list of protocol titles is provided. Accordingly it is a best practice to routinely provide the protocol forms as well as a list in advance to all IACUC members so they can make informed decisions about whether or not full committee review is needed. It is also a best practice to provide scientific documents or grant applications linked to protocols so that reviewers can understand the value of the proposed animal procedures in the context of the overall project.

These same practices are also best practices when using full committee review.

It is also a best practice to have a detailed standard operating procedure (SOP) for designated and full review to guide the IACUC members and Chairperson.

The term “designated review” is sometimes confused with the term “expedited review” when applied to IACUC reviews. However, expedited review refers to a process by which the Institutional Review Board (IRB) Chair or an experienced reviewer may conduct reviews of human research protocols that meet certain minimal risk criteria without input from other IRB members.

This expedited review procedure is not the same procedure as the designated review procedure allowed for IACUC use. The difference is that designated review can only occur if all IACUC members have the opportunity to decide that full committee review is not needed. IRB expedited review can occur without input from other IRB members.

Thus the expedited review process described for IRBs is not appropriate for IACUC reviews because it does not meet the requirements for full committee or designated review. To prevent confusion, it is a best practice to avoid the term “expedited review” as a substitute for IACUC "designated review."

After deliberating as part of a full committee review at a convened meeting of a quorum, the USDA Animal Welfare Act Regulations and PHS Policy state that the IACUC has the following options after reviewing protocols:

- Approve.

- Require modifications in the protocol (to secure approval).

- Withhold approval.

It is important for IACUC members to completely understand these review outcome options.

The first option after full committee review is to approve the protocol. This means that no modifications to the procedures or corrections to the protocol form are necessary, and the protocol needs no further IACUC action before the animal procedures can begin. Approval is good for one year (more on this later), either from the date of the IACUC meeting, or from the date on the letter to the investigator communicating the IACUC’s decision to approve. Typically, few protocols are approved outright in this manner.

The second option is the most common outcome of full committee review - to require modifications in a protocol before granting IACUC approval. When the IACUC votes to require modifications in a protocol before giving approval, it is very important that the IACUC members and investigator understand what conditions must be met before final approval can be given. At the time the IACUC communicates its concerns or requests for protocol modifications to the investigator in writing, it is a best practice for the letter to make it clear who will review the investigator’s responses to the requested modifications and who will decide if full IACUC approval can be given.

If concerns or needed protocol corrections are minor, many IACUCs allow the Chairperson or one or two IACUC members to review responses from investigators and decide if the responses are appropriate, and if approval can be given. This allows approval to be given without the need for the IACUC to meet again.

A variety of terms are sometimes used by IACUCs to describe this option, including “conditional approval”, “provisional approval”, and “approval pending.” However, such terms are not recognized by USDA and OLAW, and their usage may lead to misunderstanding between the research staff and the IACUC on the status of the protocol. It is very important that researchers recognize that this outcome does not represent IACUC approval of the protocol !!

It is best if these terms are avoided, but if they are used, it is a best practice to make sure the IACUC understands them completely and that correspondence to research staff makes it clear that IACUC approval has not been given, and animal studies or activities may not yet begin.

Remember, it is also a best practice for the IACUC make clear to investigators in written correspondence which modifications are needed, and what follow-up process will be used for reviewing the modifications so that approval can eventually be received.

For more serious concerns such as missing information, the IACUC may require that responses be reviewed at the next convened IACUC meeting before deciding if approval can be granted. The terms “deferred” or "tabled" are sometimes used to describe this course of action. This action is most common when protocols are missing important information or will require significant modifications.

The third review option for IACUC full committee review is withhold approval (sometimes termed "disapproval"). This option is not used often because protocols are rarely so inappropriate that approval cannot ultimately be reached pending modification. The IACUC and principal investigator can usually work together to revise procedures so that they meet ethical and regulatory requirements.

However, the IACUC must evaluate more than just proposed procedures. Principle #2 of the U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training (part of PHS Policy) states the following:

"Procedures involving animals should be designed and performed with due consideration of their relevance to human or animal health, the advancement of knowledge, or the good of society."

And remember, the investigator must assure the IACUC that the proposed work does not unnecessarily duplicate work already performed.

Thus, the IACUC must not only evaluate the procedures in an animal protocol, but must also address some aspects of scientific merit, as emphasized in guidance by OLAW. Accordingly, the IACUC may have to withhold approval even though the proposed animal procedures are appropriate.

In summary, the IACUC has the following options as an outcome for full committee review of animal protocols:

- Approve.

- Require modification of the protocol (to secure approval).

- Withhold approval.

In contrast to full committee review, when the designated review system is used, a reviewer does not have the option of withholding approval. Instead, the reviewer must request full committee review to address serious concerns that might warrant withholding approval. Thus, the options available to a designated reviewer are:

-Approve.

-Require modification of the protocol (to secure approval).

-Request full committee review.

Suppose two designated reviewers assigned to the same protocol come to different conclusions- one decides that the protocol should be modified to secure approval and the other believes that the full committee needs to review the protocol. What is the proper course of action? In this situation the protocol would need to be reviewed using the full committee review mode, as each designated reviewer has the prerogative to call for full committee review. If one of the designated reviewers requires modifications, the other designated reviewer would need to be aware of those changes and agree to them.

The options for IACUC decision-making are complicated, and so misunderstandings often arise. Accordingly, it is a best practice for the IACUC to have a written standard operating procedure (SOP) that includes:

- How the IACUC receives and reviews animal protocol forms.

- The reviewing system(s) used by the institution (full committee vs. designated review).

- The possible outcome options for each reviewer system used.

- What each outcome option means to the IACUC and the investigators.

Regardless of the outcome of an IACUC review, it is critically important to communicate the committee’s actions in writing to the principal investigator.

This is not just a professional courtesy, it is required by the USDA Animal Welfare Act Regulations and PHS Policy.

If the IACUC withholds approval, it must give the investigator the opportunity to respond to the committee’s actions in person or in writing. The IACUC is allowed to reconsider its decision (with documentation in the minutes) based on any new information provided by the principal investigator.

Although the USDA Animal Welfare Act Regulations and PHS Policy do not force IACUCs to allow investigators to respond in person (address the IACUC) unless approval is withheld, in the interest of good communication it is a best practice to allow investigators to do so at any time.

Likewise, the USDA Animal Welfare Act Regulations and PHS Policy do not force IACUCs to allow investigators to respond in writing unless approval is withheld. But because it is so important to document IACUC activities, it is a best practice to ask that investigators respond in writing when the IACUC requests modifications prior to granting approval.

Because the IACUC must communicate the reasons for not granting approval for a protocol to the investigator (for example, what modifications are necessary), and must also document its deliberations in the minutes (covered in Lesson 10), it is a best practice for IACUC members to submit written reviews of protocols that can form the basis for both the letter to the investigator and documentation of committee deliberation in the minutes. If such reviews can be submitted as word processing files, the IACUC support staff will have a much easier job of preparing both the investigator correspondence and the minutes.

IACUC protocol reviews can be categorized as follows:

1. Initial reviews.

2. Annual reviews.

3. Three-year reviews.

4. Reviews of proposed significant changes in protocols already approved by the IACUC.

The first type of IACUC protocol review is an initial review. This occurs when a new project is being planned and IACUC approval has not yet been granted for the work. Typically, the principal investigator fills out the animal protocol forms, meets with a veterinarian or designee for the veterinary consultation, then submits the forms for IACUC review.

The “Working With the IACUC” web course goes through the issues that must be considered by both the investigator and the IACUC during IACUC review.

Once approval for a protocol has been granted by the IACUC, the USDA Animal Welfare Act Regulations require the IACUC to review the protocol on an annual basis. Although the conduct of this annual review is not stipulated, it does not have to be as detailed as the initial IACUC review of a protocol.

OLAW has provided some practical guidance on this issue as follows:

"...monitoring may be done on an annual basis to meet USDA requirements. The purpose of monitoring is to ensure that no changes have taken place inadvertently in the approved activity that might require further review by the IACUC and that any new requirements of the PHS, USDA, or the institution are transmitted to the investigator. Monitoring need not require convened IACUC or designated reviewer action. A relatively simple mechanism to meet both federal requirements is to circulate annually to all investigators with IACUC-approved activities a standard form giving current basic information, including IACUC approval number, IACUC approval date, title of project, and species used. The investigator then notes that either no changes have taken place, or he/she describes any changes that have occurred. Responses are reviewed by an IACUC-designee for assessment of the changes reported. Any changes to the approved activity that are deemed of sufficient magnitude to merit further consideration may then be presented to the IACUC. All of these dispositions should be documented as official IACUC actions."

Once a protocol receives initial approval, can it be renewed indefinitely on an annual basis using the less rigorous review procedure? The answer is no. PHS Policy requires the IACUC to perform a complete review at the end of every third year. OLAW interprets this language in PHS Policy to mean that a “de novo”, or new review must be conducted. This review is known as the triennial review.

Although not addressed specified by PHS Policy, USDA states in Policy 12 that the principal investigator is expected to reconsider alternatives at least once every 3 years, consistent with the triennial review requirements of PHS Policy, and it is a best practice for the IACUC to ask investigators to update literature searches and justifications for animal use (including number of animals) for the three year period that will follow.

Note: Keeping up with annual and triennial expiration dates is very important! OLAW has made it clear that the IACUC is not allowed to administratively extend approval for a protocol beyond the expiration date at the end of the third year, and USDA would likely have the same dim view of administratively extending approval beyond annual expiration dates.

Must an investigator fill out new protocol forms for the triennial review?

Answer - there is nothing in PHS Policy that requires the completion of new forms for the triennial review. However, if old forms are used, the IACUC must be diligent in evaluating the information against current regulations and policy that may be more properly addressed in a newer version of the protocol forms.

For example, if an investigator submits a 1999 version of a protocol form for triennial review in the year 2002, the IACUC is obliged to review the forms according to the latest federal mandates:

Example 1: USDA/APHIS Policy #12 was released in late 2000. It stipulated that an investigator must provide specific information about database searches performed to meet alternatives mandates in USDA Animal Welfare Act Regulations (covered in the "Working with the IACUC" web course). The IACUC must now make sure that this added information is provided for the triennial review.

Example 2: The latest version of the Report of the AVMA Panel on Euthanasia was released in the year 2000. This document made the use of dry ice unacceptable as a means of generating carbon dioxide vapor for euthanasia. The IACUC is obligated, therefore, to assure that carbon dioxide used for euthanasia is provided by compressed gas in cylinders or another acceptable source (this topic is also covered in the “Working with the IACUC” web course).

Even though the old protocol form may not have addressed these issues, the IACUC must still remember to consider them in the three year (triennial) review. In the interest of ensuring the most complete reviews, it is a best practice for the IACUC to require that the latest version of animal protocol forms be completed for triennial reviews.

In summary, the review schedule for all approved animal activities is like this:

"Time Zero" - the Initial Review. The IACUC grants approval for one year.

Before the end of the first year - The investigator submits annual update paperwork certifying that either no changes have taken place or describing any changes that have occurred. Responses are reviewed by an IACUC-designee for assessment of the changes reported. Any changes to the approved activity that are deemed of sufficient magnitude to merit further consideration must be reviewed by the IACUC. Once all issues are addressed, the IACUC approves the protocol. This ensures compliance with the USDA Animal Welfare Act Regulations which mandate annual reviews. This is the first annual review.

Before the end of the second year-The investigator again submits annual update paperwork. Once all issues are addressed, the IACUC approves the protocol. This ensures compliance with the USDA Animal Welfare Act Regulations which mandate annual reviews. This is the second annual review.

Before the end of the third year - The investigator either submits a new protocol using the latest version of the form or updates the protocol on the existing version of the form, then submits it for a new IACUC review. Once all issues are addressed, the IACUC approves the protocol. This is the triennial review mandated by PHS Policy. It also doubles as the required USDA annual review.

The three-year review cycle begins again...

One area of confusion involves grants that provide funds for periods longer than three years. Does the triennial review rule for protocols still apply? Yes, it does. No matter how long a grant may provide financial support, the same IACUC review rules apply. Neither the IACUC nor institutional officials have the authority to administratively extend IACUC approval beyond the three-year period.

There is one other IACUC protocol review activity that is often overlooked, but very important. This review occurs when an investigator makes changes in the procedures or animals approved by the IACUC. These changes are often called “modifications” or “amendments.”

Why are these changes important? Simply put, both the USDA Animal Welfare Act Regulations and PHS Policy require the IACUC to review proposed significant changes in animal activities and approve them before they are implemented. Thus, the IACUC cannot wait until the annual or triennial reviews to find out if significant changes have occurred because the language clearly mandates a review of significant changes before they occur.

What is meant by a significant change in the protocol? OLAW has provided guidelines for identifying significant changes:

-Changes in study objectives.

-Proposals to switch from nonsurvival to survival surgery.

-Changes in the degree of invasiveness of a procedure or discomfort to an animal.

-Changes in species.

-Changes in the approximate number of animals used.

-Changes in personnel involved in animal procedures.

-Changes in anesthetic agent(s), the use or withholding of analgesics, and methods of euthanasia.

-Changes in the duration, frequency, or number of procedures performed on an animal.

OLAW has stated that institutions should develop guidelines for the IACUC and investigators to follow so that significant changes are reviewed by the IACUC appropriately prior to initiation. It is a best practice for the IACUC to construct a form less detailed than the protocol review form to facilitate the submission and review of modifications or amendments.

How can an IACUC remain in compliance for the four types of reviews? Some keys to remaining compliant are to:

- Maintain thorough and complete IACUC records, and

- Make investigators aware of their responsibility to request and receive IACUC approval for all animal procedures before they begin, and to receive IACUC approval for significant changes before they are implemented (these topics are covered in the “Working with the IACUC” course).

Accordingly, it is a best practice to encourage investigators to call the IACUC Chair, the veterinarian, or another Committee member to find out if a proposed change is a significant one that requires IACUC approval.

Finally, in addition to creating modification forms, a best practice is to include in the initial protocol review forms a definition of what changes are considered significant. Some institutions ask investigators to commit to notifying the IACUC of significant proposed changes on a signature page of the animal protocol forms.

Simply put, it is imperative that IACUC deliberations and actions be documented in writing. The saying that if it isn't written down, it didn't happen applies to IACUC business.

To properly document IACUC actions, it is very important (and a best practice) that consistent parliamentary procedures be used during the meeting. This allows an open and full discussion of business items, and also helps to ensure that committee actions comply with the law.

Robert's Rules of Order provides a very thorough treatment of parliamentary procedure, but the rules are overly complex for most IACUC business items. Usually a set of procedures derived from these complex rules are used for business. Whatever procedures are used, it is important that they be consistent with regulatory requirements and it is a best practice to write them down as part of an IACUC operations SOP. For an example of simplified parliamentary procedures that might be used for IACUC review of protocols, click here.

The IACUC minutes are important because they document IACUC actions for demonstrating compliance. However, they fulfill another very important function as well- assuring the public that animal activities are being conducted according to high standards, that the IACUC is monitoring animal use activities on an ongoing basis, and that any problems are identified and corrected within the institution.

Opinions vary on exactly how minutes should be kept and what level of detail must appear, but the basic concepts are that the minutes should allow an outside observer to understand what deliberations took place during an IACUC meeting, and verify that the IACUC is meeting its legal mandates.

Providing adequate support for IACUC activities can be a daunting task- preparing the minutes, filing, distributing review packets, and preparing correspondence all require significant institutional resources. AAALAC has addressed this issue in a newsletter article:

"One impediment to maintaining detailed IACUC records is a lack of adequate administrative support for the committee. Often administrative resources are minimal or nonexistent, which makes producing the minutes an additional burden on limited staff time..."

Given the fact that many institutions find it difficult to provide optimal support for the IACUC, some consideration should be given to reducing the work burden on IACUC support personnel as much as possible.

As we discussed earlier, one method is to ask IACUC members to submit their reviews as word processing documents or as e-mail messages, either before or after the meeting. The administrative staff can then clip text out of these reviews to prepare the minutes, and also use the text to prepare correspondence to investigators apprising them of what action the IACUC took on their protocols. This can greatly reduce the need for staff to listen to lengthy tape transcripts, as well as improve the accuracy of minutes and correspondence sent to investigators.

On occasion, IACUC members will simply not be able to agree on issues, and a member might want to file a minority opinion that disagrees with the vote of a majority of a quorum. As will be discussed in the lesson on semi-annual IACUC facility and program reviews, both the USDA Animal Welfare Act Regulations and PHS Policy require minority opinions to be recorded in the IACUC report generated by the semi-annual evaluation. However, the USDA Animal Welfare Act Regulations and PHS Policy are silent on the issue of minority reports for protocol reviews.

Regardless, it is a best practice to give all IACUC members the opportunity to record minority opinions in the minutes for any type of business conducted. Not to do so can give the appearance of trying to suppress dissension, which can be damaging to the reputation and integrity of the IACUC, and prevent open and honest discussions of important issues.

Because the topic of semi-annual self-evaluations by the IACUC is so important, we will cover it in three lessons. In this lesson, the basic requirement for performing the evaluation and the components of the review are covered. In Lesson 12, the mechanics of performing the facilities inspection and program review are discussed. Then Lesson 13 will address the issue of deficiencies, and how they must be corrected and sometimes reported to regulatory authorities.

From a compliance standpoint, the IACUC's task of performing the semi-annual self-evaluation is very important. Both the USDA Animal Welfare Act Regulations and PHS Policy (as well as the authorizing legislation) require this semi-annual self-evaluation.

This review has three main goals:

1. Monitor the facilities and program of animal care and use to determine if they meet the standards in the USDA Animal Welfare Act Regulations and PHS Policy.

2. Identify deficiencies, create a plan and schedule for correcting any found, and make sure corrections are made.

3. Communicate the results of the review to the IO, along with any suggestions improving the facilities or program.

The self-evaluation consists of 1) an inspection of areas that house animals or that support animal use procedures, and 2) a review of the animal care and use program. As opposed to the “bricks and mortar” animal facility inspection, the review of the animal care and use program refers to activities such as training, occupational health and safety, IACUC functions, and adherence to institutional policies that ensure compliance with the USDA Animal Welfare Act Regulations and PHS Policy.

It is very important for IACUC members to understand that USDA and PHS expect that the animal facilities will be inspected AND the program of animal care and use will be evaluated during these semi-annual self-evaluations. This point is emphasized in both the USDA Animal Welfare Act Regulations and PHS Policy by the separation of the requirements into two paragraphs- one paragraph for the program review, and one paragraph for the facilities inspection.

On what must the IACUC base its semi-annual review? Not surprisingly the USDA Animal Welfare Act Regulations stipulate that the IACUC must base its review on the USDA Animal Welfare Act Regulations, and PHS Policy stipulates that the review be based upon PHS Policy, which includes the Guide for the Care and Use of Laboratory Animals.

The USDA Animal Welfare Regulations require that at least two IACUC members perform the semi-annual evaluation. The IACUC may invite consultants to assist them. Regardless, the entire IACUC remains responsible for the review.

By law, no IACUC member who wishes to participate may be excluded. And because this evaluation provides such a valuable overview of the facilities and program, it is a best practice for members to attend if possible.

Once the evaluation is complete, a report must be written summarizing the findings. What must be in the report? The report must have two general components:

- A description of the nature and extent of the research facility's adherence to the provisions of the USDA Animal Welfare Act Regulations and PHS Policy.

- Specific Identification of departures from the provisions, and the reason(s) for each departure.

Details of these components are presented in Lessons 12 and 13.

Once the self-evaluation report is written, it must be "reviewed and signed" by a majority of IACUC members. Note that a majority of all IACUC members must review and sign the report- not just the members who conducted the evaluation, or a majority of a convened quorum.

The report must also include any minority views expressed by any IACUC member.

Next the report must be submitted to the Institutional Official (IO). By reviewing the report, the IO can gain an understanding of how effective the animal care and use program is, and what resources may need to be committed to improve the program or correct deficiencies. OLAW has provided a sample form for the IACUC to use in submitting its report to the IO.

Although not required by law, it is a best practice for the IACUC to have the opportunity to discuss the results of the report in a meeting with the IO.

As described previously, there are two distinct components to the IACUC semi-annual self-evaluation - the facilities inspection and the program review.

The Facility Inspection.

What facility areas must be inspected? The USDA Animal Welfare Act Regulations and PHS Policy require that all animal study areas and animal facilities be inspected.

The definition of a study area according to the USDA Animal Welfare Act Regulations is as follows:

“Study area means any building room, area, enclosure, or other containment outside of a core facility or centrally designated or managed area in which animals are housed for more than 12 hours.”

PHS Policy uses the term “animal facility” instead of the USDA term “study area." PHS Policy defines an animal facility as follows:

“Any and all buildings, rooms, areas, enclosures, or vehicles, including satellite facilities, used for animal confinement, transport, maintenance, breeding, or experiments inclusive of surgical manipulation. A satellite facility is any containment outside of a core facility or centrally designated or managed area in which animals are housed for more than 24 hours.”

Because the 12 hour occupancy standard in the USDA Animal Welfare Act Regulations is more stringent than the 24 hour standard in PHS Policy, the 12 hour occupancy is the default standard for determining if a room should be considered an animal housing or animal study room.

If animal facility rooms usually house animals 24 hours a day, why do these definitions matter? They matter because any and all holding rooms or laboratories that keep animals for more than 12 hours at a time qualify as “study areas”, and must be evaluated during the semi-annual facilities inspection.

To summarize, the following areas must be included in the facilities inspection:

- All buildings, rooms, areas, enclosures or vehicles used for animal confinement, transport, maintenance or breeding.

- All areas housing animals for more than 12 hours.

- All laboratories in which experiments on animals are performed, including surgical manipulations.

It is a common IACUC error to forget about investigator laboratories when the IACUC plans its facility inspections. To help prevent this oversight, it is a best practice to ask for this information on animal protocol forms so an accurate list of relevant laboratory areas can be generated.

The second component of the IACUC semi-annual self-evaluation is the program review. Taken together, the USDA Animal Welfare Act and PHS Policy require that each IACUC review their program of animal care for compliance with the USDA Animal Welfare Act Regulations and PHS Policy.

Of the two components of the self-evaluation, the program review can be the most difficult to perform. This is because there are many issues to address, such as:

-Occupational health and safety.

-Training for IACUC members, researcher staff, and husbandry staff.

-The institutional disaster plan.

-Sanitation and cleaning practices.

-Surgical support and postoperative analgesia.

-Compliance with approved protocols.

-Procedures for reporting allegations of inappropriate animal care or use.

-Accessibility to veterinary care during and after typical working hours.

Because it is easy to miss important issues during the two components of the self-evaluation, it is a best practice to use a comprehensive checklist form to guide the IACUC members consistently through the evaluation.

OLAW has created a sample form for just such a purpose. It can be downloaded from the OLAW website.

Once the IACUC semi-annual evaluation has been completed, all deficiencies in both the facility inspection and program review components must be divided into one of two categories:

-Significant

-Minor or (non-significant)

The term “significant” is used in this course because it is the term used and defined in USDA Animal Welfare Act Regulations and PHS Policy. Your institution may use a different term such as “major” in place of significant.

What is a significant deficiency? A definition combining language in the USDA Animal Welfare Act Regulations and PHS Policy is as follows:

“A significant deficiency is one which, with reference to the USDA Animal Welfare Act Regulations and PHS Policy, and, in the judgment of the IACUC and the Institutional Official, is or may be a threat to the health or safety of the animals.”

What is a minor deficiency? A minor deficiency is an area or situation that is not in compliance with USDA Animal Welfare Act Regulations or PHS Policy but does not pose a threat to animal health and safety (for example, peeling paint).

However, a minor deficiency can become a significant deficiency if it is not corrected. For instance, if not corrected, a few drops of water staining the ceiling over a rack of cages can become a large leak that can threaten to drown the animals in the cages.

Who decides whether a facility or program deficiency is significant or minor? The IACUC and the Institutional Official are given the authority to do so.

To help the IACUC and IO distinguish between significant and minor deficiencies, OLAW has provided some guidelines. Examples of deficiencies that would likely be significant are as follows:

- failures in heating, ventilating, and air conditioning systems (“HVAC”).

- inoperative watering systems.

- general power failures of sufficient duration to affect critical areas.

- inadequate veterinary medical or post-surgical care for animals.

Examples of minor deficiencies in animal facilities might include:

-infrequent findings of peeling or chipped paint.

-burnt-out light bulbs.

-warped floor drain covers.

-similar problems for which immediate solutions generally are not necessary to protect life or prevent distress.

Once identified, the IACUC must provide the following for each deficiency (significant and minor) in the report:

1. A reasonable and specific plan for correcting the deficiency.

2. A schedule for completing the corrective actions.

WARNING !!! The IACUC must be very careful to set reasonable, well-considered schedules for correcting deficiencies! Regulatory authorities will hold the institution to these schedules.

If the plan to correct a significant deficiency is not completed according to the schedule set by the IACUC, the USDA Animal Welfare Act Regulations state that the failure to correct must be reported in writing within 15 business days by the IACUC, through the Institutional Official, to USDA and any Federal agency funding that activity.

PHS Policy does not have the same requirement to report a failure to adhere to the correction schedule for a significant deficiency, but PHS Policy does require that the following be reported by the IACUC through the IO to PHS, regardless of whether a corrective plan is completed according to schedule:

-any serious or continuing noncompliance with PHS Policy (including the Guide for the Care and Use of Laboratory Animals, and

-any suspension of an activity by the IACUC (we already covered this in Lesson 5).

Remember that accredited institutions must promptly notify AAALAC of adverse events relating to the animal care and use program. Examples include investigations by the USDA or OLAW, as well as other serious incidents or concerns that negatively impact animal well-being.

Although USDA does not regulate laboratory mice and rats at this time, in the spirit of responsible self-regulation, it is a best practice to consistently notify USDA, PHS (OLAW), and AAALAC whenever you must report deficiencies to USDA or OLAW, regardless of the species involved.

USDA and OLAW have a long-standing agreement to share relevant information gained on such matters with each other. The two agencies have agreed to:

"...provide one another with information concerning significant adverse findings regarding animal care and use at organizations investigated, inspected, or site-visited, and the actions taken by the agency in response to the findings", and to "provide one another with information regarding evidence of serious noncompliance with required standards or policies for the care and use of laboratory animals at organizations that fall under the authority of the participating agencies."

Because it is so important to remain aware of plans and schedules for correcting deficiencies, the IACUC should have a method of tracking progress toward correcting deficiencies.

Many institutions find that updating progress toward correcting deficiencies at IACUC meetings helps keep on track, and it is a best practice for progress toward correcting deficiencies to be documented in the IACUC minutes.

An important legal responsibility given to the IACUC is to review, and if warranted, investigate allegations of improper animal use or concerns about such use. This includes allegations from both inside and outside of the institution. Often allegations concern animal activities being performed without IACUC approval, or being conducted in ways not consistent with the information provided to the IACUC during the review process.

When raised, allegations should be taken seriously and thoroughly investigated in a timely manner. By doing so, the IACUC can move quickly to stop inappropriate activities, and prevent unfounded allegations from negatively impacting legitimate research.

There is no required process for investigating concerns expressed about animal care and use. Nevertheless, such investigations should be timely and thorough.

Because it can be unwieldy to involve the entire IACUC in an investigation, many IACUCs form a subcommittee to collect facts and report them back to the IACUC.

Because communication with institutional officials is so important, it is a best practice for the IACUC Chairperson to notify the IO as soon as allegations arise to discuss an appropriate institutional or IACUC response.

The USDA Animal Welfare Regulations and PHS Policy make no specific requirement for how the IACUC should review allegations. A best practice is for the IACUC to discuss the collected facts of the investigation during a convened meeting, decide if the allegations have merit, formally approve a course of action by a majority of a quorum, and prepare a report for the IO which includes appropriate recommendations.

Remember that if the IACUC decides to suspend an activity as a result of its investigation, it must meet in a convened meeting, and a majority of a quorum of voting members must vote to do so. If you would like to review IACUC suspensions and regulatory reporting requirements, we covered them earlier in Lesson 5.

An important final note: The IACUC, IO, and institution must keep in mind that it is against federal law for the institution to take any reprisal against any employee who reports a violation of the USDA Animal Welfare Act Regulations.

It is a best practice to maintain an open and receptive atmosphere that encourages staff members to contact the IACUC with concerns about any aspect of the animal use program.

As previously discussed, the IACUC is considered by federal agencies and AAALAC to be the self-regulatory body for animal care and use. It is given broad powers to authorize and suspend animal use by federal law. The IACUC is also given the task of reporting suspensions and serious deficiencies in the animal care and use program to institutional officials who in turn must contact regulatory officials.

With such great power comes great responsibility. If you look at animal research from the public’s point of view, animal research is conducted by anonymous people in unfamiliar places who speak in a scientific language that can be mysterious and intimidating. Without a clear understanding of how science is conducted, the public must have trust that researchers and institutions are following regulations and conducting animal research in an ethical, humane manner. An effective IACUC is critical to making sure this trust is maintained.

Although not all modern biomedical research needs to be conducted first in animals, consider Principle #3 of the Nuremberg Code of 1947:

The (human) experiment should be so designed and based on the results of animal experimentation and a knowledge of the natural history of the disease or other problem under study, that the anticipated results will justify the performance of the experiment.

And current PHS regulations governing human clinical research also recognize that animal research is often a moral imperative before subjecting people to new procedures and drugs. The section of these regulations that address the use of pregnant women, fetuses, and children in research studies states the following:

No activity to which this subpart is applicable may be undertaken unless appropriate studies on animals and non-pregnant individuals have been completed; except when the purpose of the activity is to meet the health needs of the mother or the particular fetus, the risk to the fetus is minimal and, in all cases, is the least possible risk for achieving the objectives of the activity;

Your role on the IACUC is essential for encouraging the responsible use of animals in research to reduce human suffering.

Thanks for taking the Essentials for IACUC Members web course!

If you found any errors or would like to suggest improvements in the course, please send an e-mail message to Dr. Michael Fallon (michael.fallon@med.va.gov).

If you are ready to take the examination that covers the content in this course, click on the Courses and Exams link at the top and right of this screen to go back to the page that shows the available courses and exams.

You will be able to see when you passed each exam to document your participation in this training. If your institution is registered with the ResearchTraining.Org site, your IACUC administrator will be able to see this information as well. Regardless, we recommend that you print a copy of your completion certificate and ask that it be placed in your IACUC files.

You may now review any lesson by choosing it on the menu to the left, or choose another option by clicking on the appropriate link above and to the right.