Online Issues

Journal Vol 49 (4)

Postapproval Monitoring and the Role of the Compliance Office

William E. Dale

William E. Dale, PhD, is Director of Animal Care Quality Assurance at the University of Missouri in Columbia.

Address correspondence and reprint requests to Dr. William E. Dale, Animal Care Quality Assurance, Animal Sciences Research Center, University of Missouri, Columbia, MO 65211 or email dalew@missouri.edu.

Abstract

Postapproval monitoring (PAM) of research animal use is becoming increasingly common, and the compliance office plays a leading supportive role for the institutional animal care and use committee (IACUC) in implementing PAM at many institutions. Several other groups—higher administration, veterinary and husbandry staff, scientific staff, and occupational health and safety—are important participants in the process, and the compliance office should strive to work collegially with them as a team that facilitates research while meeting compliance requirements. Maintaining a cooperative and open attitude and developing an interest in the science will enhance the research staff's trust in both the compliance office and the PAM program. Resources required by the compliance office to oversee PAM include adequate physical facilities, funding, personnel, and time. Of these, appropriately trained quality assurance coordinators who have the requisite interpersonal and communication skills to interact constructively with researchers are vitally important. Education is key to minimizing the possibility of postapproval noncompliance, and the director of the compliance office, together with the quality assurance coordinators, should assume responsibility for teaching the IACUC, research staff, and higher administration about compliance requirements as well as correct practices and improved techniques. Postapproval noncompliance will occur despite even the best-run PAM program, and adequate documentation and communication will be necessary to address it. The compliance office, on behalf of the IACUC, should assume a primary role in facilitating the institutional response to noncompliance.

Key Words: compliance; compliance office; compliance officer; IACUC; institutional animal care and use committee; institutional official; postapproval compliance; postapproval monitoring

Introduction

Monitoring research animal care and use is a requirement of the Animal Welfare Act Regulations (AWAR¹) and Public Health Service (PHS¹) Policy, and the institutional animal care and use committee (IACUC¹) and institutional official (IO¹) are charged with providing the necessary program oversight. PHS Policy states that the IACUC "shall review the care and treatment of animals in all animal study areas and facilities of the research entity at least semiannually to evaluate compliance with applicable guidelines" (NIH 2002). The AWAR requirement is the same but explicitly permits the IACUC to determine the best means of conducting program and facility evaluations, thereby providing the opportunity to identify mechanisms in addition to semiannual inspections to help ensure compliance. Postapproval monitoring (PAM¹) programs are becoming increasingly commonplace as the research community recognizes that granting and regulatory agencies, legislative bodies, and the general public insist on increased accountability for money spent on research (Mahoney 1999). But the possibility of expanded monitoring is viewed with alarm by some scientists who regard PAM as another unfunded regulatory expectation that may interfere with research.

Although PAM has a negative reputation in some circles, a fair assessment of its value to the care and use of research animals should lead to a different characterization. A well-designed and efficiently run PAM program can benefit the research process by supporting:

the institution and administration, by minimizing the possibility of noncompliance, which can negatively affect the research enterprise;
the researchers, by helping them avoid noncompliance, which can drain time, energy, and resources from their primary responsibilities;
the animals, which receive better treatment during all phases of the experimental work as well as improved husbandry and veterinary care; and
the science, which will be more consistent and of higher quality as a result of improved care for the animals.

The director of the compliance office (i.e., the compliance officer or CO¹) and his/her staff, working on behalf of the IACUC, often have significant responsibility in ensuring institutional conformity with federal regulatory requirements. The purpose of this article is to examine the compliance office's role in a PAM program. The first section presents an overview of the groups relevant to PAM and the role of each, followed by a discussion of the best approach to achieving cooperation among them. Next is a discussion of compliance office resources and staffing, along with a compliance office–based model of a PAM program. This is followed by a description of preventive measures, focusing on education and training to help prevent postapproval noncompliance. Finally, as missteps can occur even with an effective PAM program, suggestions are presented regarding the compliance office's response to noncompliance; this section addresses the office's role in helping the IACUC, and most importantly the scientific staff, to work through the noncompliance so that the focus on research can be resumed.

Who Are the Players in a PAM Program?

The IACUC is responsible for ensuring postapproval compliance but may authorize the compliance office to develop a PAM program and implement its procedures. The compliance office is thus recognized in this article as a hub through which the program is administered, although it does not assume this role in isolation; an effective PAM program administered by the compliance office requires effort and support from the individuals and groups listed below.

IACUC. PAM may be regarded as an extension of the oversight and educational functions of the IACUC, which is ultimately responsible for the program. Identifying corrective actions and determining outcomes should be left exclusively to the IACUC as this is one of its functions (Banks 2007) and such decisions are best made following the committee's careful consideration.

Compliance officer. The compliance office director, or CO, should have responsibility for administering the PAM program and attending all IACUC meetings to keep the committee informed of PAM-related issues. In fact, the CO should be either a full or ad hoc member of the IACUC or an official consultant to the committee. The CO is responsible for communicating PAM-related issues to the IO and educating the IACUC and IO about compliance requirements.

Quality assurance coordinator(s). Individuals from the compliance office who perform PAM on-site reviews are referred to as quality assurance coordinator(s), or QAC.¹ These key staff, who report to the CO, interact directly with the animal users and observe animal procedures in laboratories and classrooms. In fact, their skills and abilities often determine the degree of a program's success or failure. To be effective, QAC must have a positive working relationship with the animal users and communicate regularly with them as well as with the CO. Through their communications with the CO, the QAC serve as the IACUC's window to the PAM program, providing observations as well as information about audits and training initiatives.

Scientific staff. PAM revolves around the scientific staff's use of animals. A good relationship between the compliance office and the scientific staff will encourage the latter to be cooperative participants in PAM rather than the subject of critical oversight. To this end, the compliance office should make clear to the principal investigators (PIs¹), technical staff, and students that the intent of PAM is not to be obstructive but rather to help maintain compliance so that the scientific work may continue without disruption.

Veterinary and husbandry staff. Those who provide medical and day-to-day care for the animals are considered partners of the compliance office in the PAM program. Because these staff provide daily husbandry care, they are acutely aware of the animals' health status and often are familiar with the experimental procedures that involve the animals. Additionally, the veterinary staff usually provide invaluable support for PAM training initiatives. It is important, however, that they not assume an enforcement role as this may lead to mistrust by the researchers.

Higher administration. Complete support of the concept and practice of PAM from the IO and his/her superior(s) is crucial for implementing and maintaining an effective program. Anything less will undermine the intent of PAM because scientific staff will be less inclined to regard it seriously. Higher administration has the additional responsibility of ensuring support for the compliance office in terms of finances, physical facilities from which to work, and adequate staffing.

Facilities management. Well-designed, well-constructed, and properly maintained facilities are an important element of good animal care and use (NRC 1996), and the compliance office should be aware of the individual(s) or office(s) responsible for facility maintenance and upkeep. Regular updates from facility management about plans for renovation or new construction are also important as such projects can disrupt research activities.

Occupational health and safety. An occupational health and safety program that focuses on maintaining a safe and healthy workplace must be part of the overall animal care and use program (NRC 1996). This requirement has taken on added importance in recent years as research using select agents and other biohazards is on the rise. In fact, biodefense and domestic security concerns produced about $4.5 billion in additional federal spending in 2001-2004 through the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (Moses et al. 2005). Well-trained and knowledgeable health and safety specialists should provide input during both protocol review and monitoring of postapproval procedures to safeguard the well-being of all personnel.

Institutional news bureau. Outreach to assure the at-large community that standards are being met is usually the responsibility of the institutional news bureau or media relations outlet. This group should be educated and kept apprised of the PAM process so that they can actively cultivate public confidence in the animal use program.

Federal agencies. Although not part of institutional infrastructure, the NIH Office of Laboratory Animal Welfare (OLAW¹) and the United States Department of Agriculture (USDA) Animal and Plant Health Inspection Service/Animal Care (APHIS/AC¹) bear directly on PAM. Compliance is scrutinized at USDA-registered facilities at least annually, and OLAW requires PHS awardee institutions to promptly report noncompliance with PHS Policy or serious deviations from the Guide for the Care and Use of Laboratory Animals (the Guide, NRC 1996; NIH 2005). In fact, the most frequent concern expressed by USDA inspectors about animal care activities has been inadequate PAM (DeHaven 2002). The PAM program should therefore ensure that the standards for animal use meet the requirements of the Guide and AWAR.

AAALAC International. The Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC¹) is not a regulatory agency and its accreditation does not guarantee that postapproval compliance problems will not occur. But the accreditation process provides an objective evaluation of an institution's animal use program, including postapproval compliance. Such feedback, done by peer review, can help identify strengths and weaknesses, and enables the compliance office to enhance the PAM program as appropriate for the institution.

The entities described above should be considered, either directly or indirectly, part of the PAM program. Again, the IACUC has ultimate responsibility for PAM, and the compliance office serves the committee by implementing and running the program. But collectively all of the foregoing groups should work together as a multidisciplinary team to make the program fully functional. The compliance office in particular should strive to work effectively with them so that PAM is carried out in an atmosphere of collegiality.

Achieving Cooperation: What Approach Works Best?

There are several ways to achieve a spirit of cooperation, especially between the scientific staff and the compliance office staff. As an instrument of the IACUC, the compliance office can be the driving force behind a successful PAM program. Problems will arise if the CO and QAC interpret their roles in ways that are incompatible with a collegial and supportive environment. For example, too commonly, and much to the disadvantage of the researchers, a CO or QAC assumes the role of a dictator whose interpretation of regulations and requirements is always right. Another nonproductive role is that of a policeman whose self-appointed duty is to enforce the Guide as a set of prescriptive engineering standards that have no room for interpretation beyond that of the CO or QAC. Those who use either approach are usually persona non grata from the scientists' viewpoint, resulting in antagonism, unnecessary problems for the IACUC and IO, and, inevitably, an ineffective PAM program that is regarded with mistrust by the scientific staff. A more effective alternative is a compliance office that both acts as a steward for the animals and strives to facilitate the scientific objectives of the researchers. It is this dual intent that makes effectuating a PAM program a challenge.

How to achieve this balance? A good first step is for compliance office personnel to assume a "client-friendly" approach when dealing with the research staff so that the office is viewed by the researchers as a resource in the PAM process rather than a place to be avoided. For example, compliance office staff should be aware that offers of assistance in email correspondence or conversations are appreciated by PIs and their staff. Of particular importance is the attitude of the person at the front desk of the compliance office, who greets people and answers the telephone. First impressions are of great consequence, and the compliance office often is judged in toto by the friendliness and competence of this individual.

It is also important to engender the scientists' confidence that the intent of PAM is not to be punitive but rather to be supportive, by providing education and guidance with the goal of maintaining compliance so that research can move forward. Compliance office staff should therefore be ready to work cooperatively with the scientific staff, and not let ego or pride interfere with that objective. In particular, PAM should not be used by the CO or QAC as a pedestal from which to dispense absolutes. An open mind is crucial and the CO and QAC should bear in mind that their interpretations of the regulations may not always be correct. Input from the attending veterinarian (AV¹), IO, and most importantly the IACUC should always be considered. Attitudinal adjustment may be necessary in some cases, combined with a conscious effort to be "client-friendly."

Finally, both the CO and QAC can enhance researchers' comfort level by developing an interest in their science. In doing so, they will understand the objectives and challenges involved with the research and will thus be better able to facilitate the goals of the scientific staff. Additionally, an interest in the science can only enhance the relationship between the CO/QAC and the researchers; it is useful to remember that scientists are dedicating their working lives to research, and human nature is such that they will respond positively to an appreciation of their efforts.

Resources

A PAM program requires adequate resources including funding, personnel, time, and appropriate facilities to accomplish its tasks (Klein and Bayne 2007). Office space may be shared with IACUC administration, but it is inadvisable for the CO and QAC to share an office with the veterinary care staff. The AV's ability to meet his/her primary responsibility (i.e., ensuring adequate veterinary care) may be compromised by apparent association with the compliance oversight feature of PAM. That is not to say that the AV should not be involved in other aspects of the PAM program, including assurance of clinical care, appropriate husbandry, and personnel training. In fact, the AV's active involvement in the program along with unimpeded lines of communication with the CO and QAC will ensure that these facets of PAM run properly. To this end, the AV's office should aim to partner with both the compliance office and scientific staff to ensure the highest level of animal care and well-being. Separate office space for the AV will help clarify his/her role in the process, thereby minimizing any possible perception of veterinary staff as "compliance police." Also in the context of administrative organization, the CO should not report to the AV or any animal manager or user. Rather, the CO should report through the IACUC to the IO to avoid conflicts of interest that may result from PAM concerns involving the AV or another animal manager/user. Reporting arrangements should be designed to strengthen the legitimacy of the PAM process rather than undermine it.

Financial support for PAM can be problematic as, far too often, it becomes available only on the heels of a noncompliant event or an accusation of noncompliance that impairs the animal research operation. Administrators with control of the purse strings may be reluctant or unable to provide funds a priori for a program intended to minimize the possibility of untoward events that have yet to occur. Requesting money from higher administration is frequently the first tactic, usually with varying degrees of success. An alternate approach presented by Conarello and Shepherd (2007) encourages those in need of monetary support for training programs (or in this case PAM programs) to develop a working knowledge of financial terms and concepts in order to present the need for PAM in terms of return on investment, showing in real dollars the potential cost of not supporting the program. Administrators will be far more receptive when presented with the bottom line as it affects the entire animal-based research operation. Specifically, the IO should have this information because s/he is the administrator who must have sufficient fiscal authority to approve and fund any needed program improvements (Van Sluyters and Brown 2007).

Administrators may nonetheless be hard-pressed to identify sources of funding for PAM even when presented with compelling cost-benefit data. Monetary resources might be made available from a central administrative pool by reallocating indirect cost recovery funds. Such funds, obtained from federal and some private granting agencies, are intended to help support the institutional infrastructure of which PAM should be considered a part. Another alternative may be to fund PAM from chargeback fees based on degree of use (e.g., a fee may be charged to the PI, department, or college for each protocol reviewed by the IACUC). This approach should be considered carefully, however, because it may be unpalatable to those being charged and could create animosity among the scientific staff. Furthermore, the monetary resources to cover chargeback fees might be unobtainable by young investigators just starting out or even by established scientists who are between grants. In either case, good ideas could be lost and scientific advancement slowed, which are unacceptable outcomes for everyone involved.

Identifying creative methods for cutting the cost of a PAM program are clearly preferable alternatives. For example, compliance office employees may alter or expand their job responsibilities to include PAM duties. Another way to minimize expenditures is to hire QAC on a part-time basis, an approach that eliminates the financial outlay for personnel benefits, which generally account for 25-30% of additional expenditure on top of base salaries.

PAM program staffing requirements depend in large part on the size of the institution. Smaller units may function effectively using a single compliance office administrator or IACUC member on a part-time basis, while large programs may require a team of individuals. Smelser and colleagues (2005) have provided an excellent report on PAM at a large, high-powered academic institution where three individuals work full-time to oversee the program.

Even more important than the number of people involved are the qualifications and personal attributes of QAC, who interact directly with the scientific and veterinary staffs. They must be familiar not only with the history and requirements of federal laws regarding research animal procurement and use but also with institution-specific policies as defined by the IACUC. QAC must have the training and background to enable their thorough comprehension of animal use protocols and to some degree the science behind them. General knowledge of the species used is also necessary along with an understanding of experimental methods and their effect on animal pain and distress, anesthetic and analgesic regimens, and general sterile surgical procedures. Finally, it cannot be stressed enough that QAC must have the interpersonal and communication skills to deal with scientists in a nonadversarial manner and without a heavy-handed approach. An upbeat and helpful attitude, combined with a willingness to act as the driving force behind problem-solving, will go a long way toward achieving compliance.

Practicalities: Effective Approaches to PAM

The most effective way to conduct PAM is by observation of animal use activities in laboratories and classrooms where they normally occur. On-site reviews of these activities should be performed by QAC in a nonthreatening manner that is helpful to the animal users and assures the IACUC that procedures are conducted as approved by the committee. Although all PAM programs should incorporate some type of on-site review, no two institutions will implement these in exactly the same way; myriad variables include program size, academic versus industrial setting, and the types of experimental procedures (see Banks and Norton 2008 for a description of an academic PAM program). Emphasis should therefore be on program performance and outcomes, which document to the IACUC that:

animal use protocols are complete and up to date,
animal users have received appropriate training,
occupational health enrollment and biohazard issues have been addressed,
animal use procedures conform with the approved protocol,
issues of concern identified during on-site reviews have been addressed by supplemental training or correction as needed, and
after the on-site review, the PI, staff, and IACUC have received documentation of observations (both positive and negative) and outcomes (e.g., supplemental training, protocol updates, occupational health enrollment).

Figure 1 illustrates a proposed reporting model for PAM. The reporting lines between the IO and both the IACUC and AV are federally mandated; otherwise this example may not be appropriate for all institutions. In this model, the IACUC and AV report directly to the IO, who is responsible for the animal use program. The CO reports PAM issues to the IACUC, but there should also be significant communication about the program between the CO and AV and the CO and IO. The CO, charged with program management, directly oversees the QAC, who perform on-site reviews of laboratories and classrooms where animals are used. It is crucial to involve the AV, who will both communicate routinely with the QAC about remediation of animal health and pain/distress issues and support training initiatives that may be necessary after on-site reviews.

Figure 1 Reporting structure for a postapproval monitoring program. Solid lines indicate direct reporting. Dashed lines indicate a high level of communication. AV, attending veterinarian; CO, compliance officer; IACUC, institutional animal care and use committee; IO, institutional official; QAC, quality assurance coordinator.

The QAC should schedule on-site reviews well in advance and at the convenience of the PI and his/her staff, following up with a brief outline describing what will happen during the on-site review at least several days beforehand; a courtesy telephone call reminder the day before will be appreciated. The QAC should be familiar with the animal use protocol(s) and relevant standard operating methods. During the review the QAC should observe animal use as it would be normally scheduled and avoid requesting any type of procedural demonstration only for the benefit of the PAM program—staged reenactments usually do not accurately reflect what actually happens when animals are used and they also are a waste of valuable animal resources.

On the day of the review and upon arrival at the site, the QAC should first find and introduce him-/herself to the PI. Although the PI's hands-on involvement in the procedure may be somewhat minimal, s/he should be fully briefed on the day's agenda as s/he is ultimately responsible for the animal procedure(s) that will be performed. A general outline for the on-site review schedule is as follows:

Protocol and administrative review: The QAC and animal use personnel should initially sit down together to review the approved protocol and standard operating methods applicable to the procedure that will be observed. This is an opportunity for the QAC to request clarification of any points that may not be entirely clear from the protocol, to ask for more detail about specific procedures that will be observed, and to provide supplemental training in institutional policies and responsibilities. The QAC should ensure that all personnel are listed on the protocol and are enrolled in occupational health; required training and mandatory documentation have been completed; animal housing/use sites and nonstandard husbandry requirements have been identified; and the use of infectious agents, biohazards, and radioisotopes has been approved.
Procedural observation: The PI and/or staff should be asked to conduct the procedure while the QAC observes the activity. The QAC should refrain from initiating discussion or asking questions during this time to avoid distracting scientific staff from the task at hand; instead the QAC should take detailed notes and ask questions at the conclusion of the activity. The QAC should document positive observations as well as any practices that deviate from the approved protocol or that could be improved through supplemental training.
Postprocedural review: At the conclusion of the procedure, the QAC will discuss his/her observations, taking care to approach the conversation as a give-and-take and encouraging the PI and staff to clarify or correct any misinterpretations. The postprocedural review should always start with any positive observations from the protocol and administrative review and the animal use procedure itself. The QAC should approach judiciously any points that need correction or that could be improved through supplemental training; a complete explanation of the problem, why it is a concern, and suggested steps to correct it should be the standard format for presentation of each point. The need for a protocol amendment, if necessary, should be pointed out when reviewing each of these items. Finally, the QAC should indicate that s/he will arrange for further training with the veterinary staff if needed and that a written summary of the on-site review will be forwarded to the PI, the compliance office, and the IACUC (including the AV). A global wrap-up emphasizing the positives is a good way for the QAC to end the postprocedural review.
Follow-up to on-site review: The QAC must prepare a written summary of the on-site review and send copies to the parties mentioned above. As part of the PAM program, the IACUC might consider lauding animal use sites that receive "clean" summary reports (i.e., reports with no modifications required and no additional training needed) by forwarding these to appropriate upper administrators such as department heads and/or deans. In all cases, the summary report should include thorough documentation of the procedures performed, observations (both positive and negative), procedural/protocol modifications, and supplemental training that was provided. The QAC should apprise the CO of notable or potentially controversial observations or recommendations made during the on-site review so that s/he can communicate knowledgeably about these with the IACUC, AV, and IO. The QAC may provide training for protocol and administrative requirements or basic animal handling; the AV and his/her staff are responsible for more technical training, such as specific surgical techniques or use of analgesics and anesthetics. The QAC should arrange for such training when it is needed and work closely with the AV's office to ensure their support. The QAC should also verify that the PI has amended the protocol, if necessary, following the on-site review. Finally, when all is done, the QAC will serve the program well by sending a follow-up note to the PI and staff thanking them for participating in the PAM process.

Minimizing Postapproval Noncompliance

A team approach has been identified as key to minimizing the possibility of noncompliance (Klein and Bayne 2007). In this approach, the IACUC, veterinary and husbandry staff, administration, facilities management, occupational health and safety, public relations, and research investigative staff work together to support the compliance office in providing broad-based oversight, thereby ensuring an effective PAM program. It is important that the CO and QAC serve as liaisons between scientific staff and these other groups, as the researchers may have understandable reservations—after all, scrutiny of their compliance with animal use protocol and institutional requirements is the focus of PAM.

Staying abreast of the latest information in the animal care field is an important way for the CO and QAC to help minimize the possibility of noncompliance. There are many educational opportunities available including print publications, online materials, and conferences and meetings (Haywood et al. 2005). Staying up to date with the latest communiqués from OLAW, USDA, and AAALAC is also essential. Key personnel at AAALAC-accredited institutions can receive Keeping Connected, an electronic bulletin with the latest articles and information from the animal care and use community. Also, anyone with an email address can sign up to receive APHIS press releases automatically, and OLAW has created a listserv that provides information about implementation of PHS Policy, educational workshops, and other programs designed to foster compliance. Regular visits to these organizations' websites are another good way to obtain information, and these groups are happy to assist with interpretation of requirements—the CO should not hesitate to contact them for clarification on any topic that falls under their area of oversight. Other listservs such as IACUC-Admin (hosted by Michigan State University), IACUC-Forum, and CompMed (hosted by the American Association for Laboratory Animal Science, AALAS) can serve as informal yet valuable discussion venues on topics related to research animal use. More often than not, one or more of these three sites references information from OLAW, USDA, and AAALAC, making them useful tools for staying abreast of recent policy statements and announcements from these agencies.

A well-informed compliance office can be a valuable resource to the institution, but only if the relevant information is imparted to those who need it. The CO and QAC (interacting primarily with the IACUC/IO and animal users, respectively) must be "teachers" who convey knowledge so that problems can be averted or rectified. Thus, education is another key to avoiding postapproval noncompliance. There are three groups of primary consideration for education and training: animal users, the IACUC, and the IO.

Animal Users

Federal requirements mandate that animal users receive appropriate training (AWA 1996; NIH 2002) and that PIs, students, and technical staff clearly understand performance standards. In the context of PAM, there are many ways for the QAC to deliver training effectively to those on the front lines of animal use (Conarello and Shepherd 2007; Medina and Anderson 2007; Romick et al. 2006). Electronic media (e.g., computer/web-based resources, CDs, and DVDs) have become convenient and commonly used mechanisms, but the tried and true didactic presentation provides the added benefit of give and take between the trainer and trainee. Similarly, email is a wonderful communication/educational tool and progress at many institutions would grind to a standstill without it; nevertheless, direct contact by telephone or, ideally, face-to-face discussion allows for a level of understanding and clarity that may be lost in an electronic message.

Institutional Animal Care and Use Committee

The AWAR imply that IACUC member training is expected (AWA 1990), and APHIS Animal Care Policy #15 indicates that the research facility is responsible for training to ensure that IACUC members have an understanding in areas such as the Animal Welfare Act, protocol review, and facility inspections (APHIS 2006). Also, the Guide (NRC 1996, 9) states that "It is the institution's responsibility to provide suitable orientation . . . and, if necessary, specific training to assist IACUC members in understanding and evaluating issues brought before the committee." The CO typically is responsible for educating the IACUC members about compliance-related issues. Training and orientation for new members may actually begin during the selection process for their appointment, with explanations of their responsibilities and time commitment (Greene et al. 2007). Formal orientation should provide a thorough overview of requirements and expectations, along with a clear explanation of how the IACUC meets its obligations. Continuing education for IACUC members usually occurs during regularly scheduled meetings; the CO may present information in various formats (Haywood et al. 2005). The committee's interest often can be piqued by selecting training topics of current relevance to the institution.

Institutional Official

Because IO support is a requirement for a successful PAM program, and in order to provide this backing reliably, the IO must be informed about federal, state, and local requirements as well as the implications of noncompliance. It is naïve to presuppose that the IO is knowledgeable in such matters and it may even be disastrous for the institution in a time of crisis. The CO should meet regularly with the IO or, if appropriate, his/her designated lieutenant to ensure that higher administration is aware of new regulations and requirements as they occur.

Noncompliance Rears Its Ugly Head: What to Do Now?

A PAM program can help decrease but not eliminate the incidence of noncompliance. Mistakes usually result from ignorance, or, occasionally, from a rebellious researcher's decision not to meet the required standards. Minor noncompliant events often can be addressed administratively by the compliance office without the involvement of other entities. More serious incidents usually require a broader response that involves other institutional offices and possibly external agencies. In any case, the CO should assume primary responsibility for ensuring an adequate response. Actions and conversations should be documented and, along with all written correspondence, dated and retained in case the information is needed for formal reports to federal agencies, higher administration, or the IACUC. Also, depending on the nature of the issue, it is important to notify the following appropriate people of the problem:

IO and other higher administration: These individuals can ill afford to be caught off-guard on issues of noncompliance because they are the public face of the institution. As the person with the authority and responsibility to enforce and supervise the AWAR and PHS Policy requirements (Schiffer 1999), the IO in particular must be briefed on significant issues as they occur. It is far better that s/he learn of problems from the CO than from a representative of the local media. Other administrators that should be kept in the loop include department chairs and deans or program directors.
IACUC and AV: The committee, which includes the AV, is required to oversee the institution's animal program, facilities, and procedures and to make recommendations to the IO when changes are needed (NIH 2002). The IACUC must therefore be well informed about all problems related to postapproval noncompliance in order to effectively carry out its responsibilities. Updates from the CO about issues of noncompliance should be a regular item on the committee's meeting agenda.
OLAW: The PHS Policy calls for a system of self-evaluation, self-monitoring, and self-reporting for any institution with an Animal Welfare Assurance (NIH 2005). This enables OLAW to monitor an institution's animal care and use program oversight under the Policy and to evaluate allegations of noncompliance. OLAW's Division of Compliance Oversight monitors the program and open, honest communication with this office is expected when reportable activities occur. The Division of Compliance Oversight also can provide helpful feedback if there is any uncertainty on the part of the institution about the need to report potential noncompliance.
USDA APHIS/AC: The AWAR (§2.31(c)3) require that any uncorrected significant deficiency that involves species covered under the Animal Welfare Act and that is noted in the semiannual report to the IO be reported to APHIS/AC and any federal funding agency (Silverman 2007). It is not necessary to report noncompliant issues not included in the semiannual report. Nevertheless, if a covered species is involved, it may be helpful to keep the institution's USDA veterinary medical officer informally in the loop as s/he will likely become aware of the noncompliance during the next inspection anyway. In addition, this person's feedback may be valuable in addressing the issue.
AAALAC: Accredited institutions should notify AAALAC of any instances of serious noncompliance that have been reported to OLAW or APHIS/AC. These will be reviewed by site visitors as background information during the triennial reaccreditation process.

A group effort is often required to address postapproval noncompliance so the CO should not shoulder all responsibility for decisions or actions. Responses should be formulated collectively after careful thought and consideration of the issue(s). Clearly, as the group charged with responsibility for ensuring postapproval compliance, the IACUC must play a primary role and the CO can help by providing the committee with regulatory information along with updates on progress toward achieving a resolution. Generally, the CO should act as a conduit of information between the IACUC and the federal oversight agencies, the IO, and, importantly, the researchers involved.

Finally, the compliance office should facilitate the institution's efforts to work through specific issues of postapproval noncompliance. Such problems rarely resolve themselves and neglect may lead to more serious consequences. The CO and staff should do the hard work necessary to reach an appropriate resolution of the noncompliance.

Summary

The compliance office can play a key role in the PAM program, the structure and mechanics of which will be unique to each institution. Several points hold true regardless of the procedures employed:

The IACUC is responsible for ensuring postapproval compliance and PAM is a mechanism by which the committee can meet this requirement. Not uncommonly, the IACUC will designate responsibility for program implementation and oversight to the compliance office, which then serves as the administrative department through which the program is run. The CO should report directly to the IACUC and communicate regularly with the IO about noncompliance or other issues related to PAM.
The compliance office should make an effort to involve all internal players in PAM—the IACUC, veterinary and husbandry staff, researchers, the IO and other relevant administration, facilities management, occupational health and safety, and the institutional media relations office. Federal oversight agencies and AAALAC should also be considered part of the PAM program indirectly as they can provide feedback and demand accountability for postapproval noncompliance.
Compliance standards must be maintained, but a dictatorial approach in executing PAM is inadvisable—heavy-handed oversight may produce more negative than positive outcomes. The compliance office should cultivate a reputation as a resource for investigators rather than a hurdle to be surmounted when faced with compliance issues.
The resources necessary for the compliance office to administer PAM include office space (ideally located separate from the veterinary staff) as well as adequate funds and personnel to support the program. The background and qualifications of QAC, along with their ability to communicate effectively with researchers, are critically important in developing a team approach to PAM.
The CO should report through the IACUC to the IO, never to the AV or any other animal manager or user, which may invite serious conflicts of interest.
The purpose of PAM is to assure the IACUC of adherence to administrative and animal use procedural standards. On-site reviews conducted by well-qualified QAC are an effective means of monitoring postapproval compliance. The QAC should plan the review well in advance and ensure that the PI and animal use staff understand the process. They should conduct the on-site review in a collegial manner and use it as a teaching opportunity whenever possible. After the review, the QAC should make arrangements for supplemental training, if needed, in cooperation with the AV and his/her staff. The QAC must then provide a written summary of the review to the PI, the compliance office, and the IACUC. Notably deficient or possibly contentious items identified during the on-site review should be discussed in detail with the CO so that s/he can keep the IACUC and IO informed of these issues.
The possibility of postapproval noncompliance can be minimized if the CO and QAC keep current with the latest regulatory requirements so that they can provide training when necessary. The QAC should educate researchers on these issues during on-site reviews, and the CO should ensure that the IACUC and IO receive this information.
The CO and QAC should act as liaisons between the scientific staff and other institutional groups in order to promote a team approach to PAM. Electronic methods of interface can be efficient tools for achieving this objective, but in most cases verbal interaction by telephone, face-to-face discussion, or in a classroom setting is the most effective means of communication and education.
Some postapproval noncompliance is a virtual certainty, even at institutions with well-run PAM programs. Resolving noncompliant issues is part of PAM and the CO should assume a lead role in this effort. Thorough documentation is required and open communication with the scientific staff as well as between the IO, IACUC and AV, relevant federal agencies, and AAALAC, if applicable, is essential. The IACUC and IO are officially responsible for addressing noncompliance, and the CO can support them by working proactively toward a satisfactory resolution.

A good PAM program strengthens animal care and well-being and, just as importantly, enhances the quality of science. The compliance office can play an important part in ensuring that PAM is effective and beneficial for the animals, the researchers, the IACUC, and the institution.

Abbreviations used in this article: AAALAC, Association for Assessment and Accreditation of Laboratory Animal Care International; APHIS/AC, Animal and Plant Health Inspection Service/Animal Care; AV, attending veterinarian; AWAR, Animal Welfare Act Regulations; CO, compliance officer; IACUC, institutional animal care and use committee; IO, institutional official; OLAW, Office of Laboratory Animal Welfare; PAM, postapproval monitoring; PHS, Public Health Service; PI, principal investigator; QAC, quality assurance coordinator(s)

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