Postapproval monitoring and the IACUC

Monitoring of the use of live vertebrate animals in research, teaching, and testing after approval of their use by an institutional animal care and use committee (IACUC) are receiving increased attention in the laboratory animal community. In this article the author provides his opinions on the value of postapproval monitoring (PAM) to the overall self-regulation that is the responsibility of an IACUC. PAM must never supersede or replace federally mandated IACUC responsibilities, but an efficient PAM process can provide significant additional information that enables an institution to be confident that it is meeting both the letter and the spirit of the federal regulations developed to ensure humane animal care. PAM personnel should be excellent communicators and able to maintain a professional demeanor in challenging circumstances. Their knowledge of laboratory animal care, invasive procedures, and regulations will enable them to align the pursuit of scientific research with adherence to these regulations. An effective PAM program involves knowledgeable individuals who can, on behalf of the IACUC, monitor new procedures and personnel and provide IACUC-mandated training or retraining.     

Training strategies for IACUC members and the institutional official

Institutions are required by federal laws and regulations to oversee and evaluate their programs, facilities, and procedures for using animals in research, teaching, and/or testing activities. These responsibilities are specifically charged to an institutional official (IO) and an institutional animal care and use committee (IACUC). Initially, the individuals tasked with these responsibilities seldom have the requisite knowledge or experience to fulfill their charges effectively. Furthermore, simply reading the regulatory requirements does not prepare the novice IO and IACUC members to effectively monitor and guide the program. As a result, many new IOs and IACUC members are managing their responsibilities with insufficient understanding of the laws, regulations, standards, and policies. Specific training strategies for inexperienced IACUC members are needed to help them understand their responsibilities for ensuring animal welfare through an effective, high-quality, and compliant animal care and use program that supports the critical research needed to improve human and animal health. Likewise, most IOs would benefit from training to help them better understand their responsibility for enhancing or maintaining the quality of the institution's animal care and use program. Education and training should begin with an orientation to the laws, regulations, standards, and policies. Continuing training and education are also important to keep abreast of the changes in the interpretation of these laws and regulations as well as the changes in veterinary science. For both the IO and the IACUC, understanding and acceptance of their authority and responsibilities are significant factors in establishing and maintaining a quality animal care and use program.     

A sample postapproval monitoring program in academia

The primary goal of an animal care and use program (ACUP) should be to ensure animal well-being while fostering progressive science. Both the Animal Welfare Act (and associated regulations) and the Public Health Service (PHS) Policy require the institutional animal care and use committee (IACUC) to provide oversight of the animal program through continuing reviews to ensure that procedures are performed as approved by the committee. But for many committees the semiannual assessment does not provide an opportunity to observe research procedures being performed. Furthermore, IACUC members are typically volunteers with other full-time commitments and may not be able to dedicate sufficient time to observe protocol performance. Postapproval monitoring (PAM) is a tool that the IACUC can use to ensure that the institution fulfills its regulatory obligation for animal program oversight. When performed by attentive and observant individuals, PAM can extend the IACUC's oversight, management, training, and communication resources, regardless of program size or complexity. No defined PAM process fits all institutions or all situations; rather, the monitoring must match the program under review. Nonetheless, certain concepts, concerns, and conditions affect all PAM processes; they are described in this article. Regardless of the style or depth of PAM chosen for a given program, one thing is sure: failure of the IACUC to engage all available and effective oversight methods to ensure humane, compassionate, efficient, and progressive animal care and use is a disservice to the institution, to the research community and to the animals used for biomedical research, testing, or teaching.     

Program oversight enhancements (POE): the big PAM

Federal animal welfare regulations and policies require compliance during animal research. But the methods used to oversee, assess, and ascertain compliance are left in the hands of the research institution and its institutional animal care and use committee (IACUC). Differences in institutional cultures, research goals, individuals responsible for animal care and use activities and oversight, and availability of financial and personnel resources have given rise to a variety of institution-specific mechanisms for ensuring compliance with the federal requirements and specifically with IACUC-approved animal research activities. In recent years one such mechanism, postapproval monitoring (PAM), has risen in popularity. An often cited topic in animal welfare-related conferences and periodicals, it is well on its way to becoming a compliance standard. However, it is but one mechanism for ensuring postapproval compliance and is not required by the federal animal welfare regulations. In this article we describe alternative mechanisms for ensuring compliance with IACUC-approved animal research through the use of program oversight enhancements (POE) in the context of an institution's animal care and use program. We present these enhancements in a way that allows readers to pick and choose those of interest. While these methods may not be feasible at all institutions, adopting even a few should improve a program's ability to ensure compliance with approved animal research and reduce the need for an aggressive and formal postapproval monitoring process.     

The institutional official and postapproval monitoring: the view from 10,000 feet

The role of the institutional official (IO) in ensuring a high-quality program of laboratory animal care and use has received relatively little attention in the literature compared to that of the institutional animal care and use committee (IACUC) or attending veterinarian. Yet the IO is critical to institutional effectiveness. Often not a scientist, especially at colleges and universities, the IO is an executive who bears ultimate responsibility for the care and use of laboratory animals. An IO operates largely through delegation to the IACUC and the institutional veterinarian, yet must maintain a clear view of the program from the executive level--the "view from 10,000 feet." To do so, the IO must bring four critical leadership qualities to the position: (1) vision, (2) a commitment to quality and integrity, (3) strong planning and resource development, and (4) accountability to the laboratory animal program. The IO's ability to act on these qualities and to evaluate the effectiveness of the resulting program requires reliance on a strong program of postapproval monitoring (PAM). Summary data from PAM, based on metrics carefully defined by the IO in consultation with the IACUC and the institutional veterinarian, provide the feedback necessary to guide executive decisions and allow the IO to place the needs of the program of laboratory animal care and use successfully into the larger context of the mission of the institution.     

Training strategies for research investigators and technicians

Training programs for research personnel are discussed as a key resource that must be part of an effective animal care and use program. Because of the legal responsibility to ensure that research staff are qualified to use animals, many institutions have justified the necessity for a training coordinator and/or trainers for their animal care and use programs. Effective training programs for research personnel must meet the needs of the client base (research scientists and staff) so that they are relevant, practical, and timely. To meet these objectives, it is useful to involve the scientific staff in the analysis of their learning needs. To meet a performance standard necessary for quality research, a large percentage of the institutional staff must participate in the training program. Often it is the principal investigators who set the tone for their staff members regarding the importance of receiving training. Garnering support from this client base will create a culture that encourages training and engenders a positive attitude about humane animal care and use. One effective approach is to incorporate nonanimal models as alternatives to live animals to teach humane handling techniques and methods, thereby contributing to refinement, reduction, and replacement (the 3Rs). Also discussed are the necessity of timely feedback from clients, documentation of personnel training for regulatory purposes, and the collection of training metrics, which assists in providing justification for the granting of additional fiscal support for the program. Finally, the compliance procedures and opportunities for essential refresher training are discussed and related to high performance standards, humane animal use, and quality research, all of which contribute to the 3Rs.     

Engaging the IACUC through comprehensive training

The IACUC is one of the most important committees at a research institution and plays a critical role in the success of an animal care and use program. It is the responsibility of the institution to provide IACUC members with adequate and appropriate training. The authors explore various IACUC training options.     

Fundamental training for individuals involved in the care and use of laboratory animals: a review and update of the 1991 NRC Core Training Module

Public trust demands that individuals who do research, testing, or teaching with animals use humane, ethical, and scientifically sound methods. Furthermore, the Animal Welfare Act and the Public Health Service Policy require research institutions to provide basic training and to ensure that anyone who cares for and/or works with laboratory animals has the appropriate training or experience relevant to their job responsibilities. Institutions accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International must also provide training programs and ensure the qualifications of personnel. The primary goal of this training is to provide individuals with basic knowledge and to reinforce attitudes and behaviors that help to ensure humane animal care and use. This article provides an overview of the core training module outline and content from the 1991 report of the Institute for Laboratory Animal Research, Education and Training in the Care and Use of Laboratory Animals: A Guide for Developing Institutional Programs, as well as pertinent updates for introducing personnel to information regarding the care and use of laboratory animals. Both mandatory and suggested training topics are reviewed, including relevant regulations and standards, ethical considerations, humane methods of animal experimentation and maintenance, and other pertinent topics. Although the fundamental training course content and delivery will vary depending on the nature and complexity of an institution's animal care and use program, this basic training provides the foundation for more in-depth training programs and supports humane and ethical animal care and use.     

Avoiding an overzealous approach: a perspective on regulatory burden

The authors discuss the impact of regulatory burden on the research enterprise, with emphasis on animal care and use programs. They identify three sources of regulatory burden: specific requirements in law and regulation, interpretive requirements or "guidance" by regulatory agencies, and self-imposed regulatory burden resulting from institutional interpretations. Attempting to minimize the risks of noncompliance through the overzealous application of "requirements" does not necessarily benefit the animals. Balancing risks associated with animal research and burden in a successful program requires clear and consistent communication among all stakeholders--the institutional leadership, institutional animal care and use committee (IACUC), attending veterinarian and staff, and scientists. An evaluation tool is provided for institutions to assess their approach to required and voluntary activities in their animal care program. Drawing on the knowledge and experience gained in a combined 40 years of serving on, managing, training, and evaluating animal care programs, the authors conclude that institutions must thoughtfully balance their research and compliance needs to successfully maintain their institutional goals. They stress that a culture of compliance based on knowledge of the regulations, dedication to quality animal care, reasoned use of science-based performance standards, and the judicious application of professional judgment is the foundation for facilitation of research in the context of animal welfare and regulatory compliance.     

Enrichment and primate centers: closing the gap between research and practice

A wealth of published research is available to guide environmental enrichment programs for nonhuman primates, but common practice may not consistently correspond to research findings. A 2003 survey to quantify common practice queried individuals overseeing enrichment programs about (a) social, feeding, structural, and manipulable enrichment; (b) human interaction and training; (c) general program administration; (d) the role of the institutional animal care and use committee (IACUC) in the enrichment program; and (e) the impetus for recent programmatic changes. Returned surveys provided information on the management of 35,863 primates and found social housing significantly more constrained than inanimate enrichment. Survey results suggest that social housing of macaques has not increased significantly over the past decade. The most commonly mentioned constraints related to research protocols. Facilities with thorough IACUC reviews of enrichment issues provided social housing for a significantly larger proportion of primates in biomedical research studies than did those with rare IACUC reviews. IACUC reviews prompted program enhancements much less often than did regulatory or accreditation inspections. These results suggest IACUC review is an underutilized mechanism for improving enrichment programs.     

Enrichment and Primate Centers: Closing the Gap Between Research and Practice

A wealth of published research is available to guide environmental enrichment programs for nonhuman primates, but common practice may not consistently correspond to research findings. A 2003 survey to quantify common practice queried individuals overseeing enrichment programs about (a) social, feeding, structural, and manipulable enrichment; (b) human interaction and training; (c) general program administration; (d) the role of the institutional animal care and use committee (IACUC) in the enrichment program; and (e) the impetus for recent programmatic changes. Returned surveys provided information on the management of 35,863 primates and found social housing significantly more constrained than inanimate enrichment. Survey results suggest that social housing of macaques has not increased significantly over the past decade. The most commonly mentioned constraints related to research protocols. Facilities with thorough IACUC reviews of enrichment issues provided social housing for a significantly larger proportion of primates in biomedical research studies than did those with rare IACUC reviews. IACUC reviews prompted program enhancements much less often than did regulatory or accreditation inspections. These results suggest IACUC review is an underutilized mechanism for improving enrichment programs.     

Global harmonization in the care and use of laboratory animals for the space life science research]

Space researches are supported with the international space agencies, NASA and NASDA. Animal experiments on the space life science must conform to the NIH policies and the NASA guide for the care and use of laboratory animals. The goal of the NIH policies is to promote the humane care of animals used biomedical and behavioral research, teaching, and testing. In each institute, the Institutional Animal Care and Use Committee (IACUC) plays an important role in conformity with NIH policies. The IACUC is charged with developing, recommending and monitoring NIH/NASA (ARC and KSC) policies, guides and rules relating to animal acquisition, care and use. In ARC and KSC, investigators will be responsible only for activities directly related to the conduct of their animal experiments. Even if researchers have protocols of the space science in Japan, the animal experiment should be carried out under the global harmonized conditions in accordance with NIH policies and NASA guides.     

Establishing a culture of care, conscience, and responsibility: addressing the improvement of scientific discovery and animal welfare through science-based performance standards

Science-based performance standards offer a viable means of reducing regulatory burden while ensuring that research animal welfare and high-quality research data are realized. Unlike rigid regulations, science-based performance standards evolve as new information becomes available, thereby allowing new discoveries to be implemented in a timely manner and in a way that more effectively benefits the animals and the science. The implementation of performance standards requires a well-coordinated institutional team composed of the administration, research staff, the institutional animal care and use committee, professional and technical animal care personnel, occupational health and safety staff, and physical plant staff. This animal program team is best supported in an institutional environment that reflects a culture of care, compliance, and responsibility. In such a culture, the professional judgment exercised by the team is well grounded in meeting the diverse needs of the program's customers, who include the animals, the researchers, and research stakeholders such as the public. The institutional culture of care, compliance, and responsibility fosters workplace integrity, an ethics-based decision-making paradigm, sound understanding of institutional expectations through good communication and clear lines of authority, the hiring and retention of trained and well-qualified individuals, and a system for continuous development and improvement of the program.     

Postapproval monitoring and the role of the compliance office

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.     

A training primer for Institutional Officials

The laws and policies governing the care and use of animals in research in the US require institutions to establish training programs to assure that personnel are qualified for their roles in animal care and use programs. Few programs define specific training requirements for the Institutional Official (IO), one of the most important roles in an animal care program. In some cases, IOs may have little or no experience in biomedical science. In this article, the author provides an overview of the IO's role in an animal care and use program as defined by US government laws and policies for use in training IOs and chief executive officers. The author outlines the key responsibilities of the IO in an animal care program, the implications of noncompliance with federal requirements and some of the pitfalls in program design.     

Preparation of animals for use in the laboratory: issues and challenges for the Institutional Animal Care and Use Committee (IACUC)

Preparation of animals is important for optimization of animal welfare as well as to minimize interanimal variation, thereby strengthening the quality of data for in vivo studies. These issues are important in the work of institutional animal care and use committees (IACUCs), but they pose many challenges as well. This article provides IACUC members with a resource for use in determining whether and how preparation of animals for research affects the IACUC's responsibilities. The topics addressed are intended to serve as a starting point for consideration and discussion. Questions related to subject selection and acclimation of subjects to experimental housing and procedures are emphasized and should provide IACUC members with a framework for discussion of relevant questions. Guidelines are provided for promoting the acclimation of a number of species to experimental settings. Additional, potentially controversial points are also raised, including the effects on longitudinal data sets of changing subject preparation procedures. The roles of the IACUC in the research endeavor are multifaceted and continuously evolving. As empirical data are produced that affect additional aspects of animal care and use, it is important for these committees to be able to evaluate and, when appropriate, stimulate the implementation of improved procedures and strategies.     

A guide to risk assessment in animal care and use programs: the metaphor of the 3-legged stool

A high-quality contemporary animal care and use program (ACUP) is a multifaceted dynamic system with three distinct organizational entities--the institutional official (IO), attending veterinarian (AV), and institutional animal care and use committee (IACUC)--each of whose authorities and responsibilities are mandated by a complex set of laws, regulations, policies, and guidelines. The 3-legged stool is presented here as a metaphor for the properly constituted and functioning ACUP, with the legs of the stool representing the IO, AV, and IACUC: when one component is weakened, the stool remains standing but tilts--the ACUP remains in compliance with animal welfare standards but is at risk of failure. Mechanisms for assessing an ACUP's strengths and weaknesses include both external evaluators, such as the US Department of Agriculture, Office of Laboratory Animal Welfare, and Association for Assessment and Accreditation of Laboratory Animal Care, and internal evaluators, such as the IACUC, AV, and IO. However, each of these evaluators primarily assesses whether aspects of the ACUP are in compliance with current standards; they do not necessarily cite weaknesses in a compliant program. This article stresses the need for ACUPs to undertake a self-assessment of risk and outlines a number of ways programs can recognize their risks, with examples for each of the three components, which are characterized as either "weak" or "overzealous" in meeting their mandates. I caution against the use of a legacy of compliance as the sole means for evaluating an ACUP's strength, and instead promote the value of rigorous risk assessment/mitigation to ensure that a program is both strong and resilient.     

IACUC issues associated with amphibian research

Numerous species of amphibians are frequently utilized as animal models in biomedical research. Despite their relatively common occurrence as laboratory animals, the regulatory guidelines that institutional animal care and use committees (IACUCs) must employ provide little in the way of written standards for ectothermic animals. Yet, as vertebrates, laboratory amphibians are covered by the National Research Council Guide for the Care and Use of Laboratory Animals and the Public Health Service (PHS) Policy for federally funded research. This article focuses on three issues that are relevant to IACUC oversight of the use of amphibians in research: (1) recommended educational requirements of investigators and animal care staff engaged in research with amphibians, (2) zoonoses and other issues of occupational health importance, and (3) indicators of stress and disease. Addressing these issues should enable investigators, IACUCs, and animal care staff to meet the regulatory expectations of the PHS and accrediting bodies such as the Association for Assessment and Accreditation of Laboratory Animal Care International.     

Training strategies for animal care technicians and veterinary technical staff

An institutional training program for animal care and veterinary technicians should be planned and implemented to provide these individuals with knowledge and skills for performing their duties within a laboratory animal care and use program. The complexity in the regulatory and scientific features of the animal research environment necessitates a strong training program on diverse topics according to staff duties. Orientation training should include ethics and compliance with relevant laws, policies, and guidelines. Depending on specific staff responsibilities, training may be general or in depth on topics of species-specific biology and behavior, animal facility equipment and operations, animal health procedures, animal research policies, occupational health and safety equipment and practices, computer usage, training, and management. Staff training should be an ongoing mission for incorporating new equipment, practices, and procedures in the laboratory animal program; for providing periodic refresher training to maintain a high level of staff qualifications; and for retraining when skills or knowledge are found deficient. Large institutions often have a dedicated training staff to implement the institutional training program.