TY - JOUR
AU - Anderson, Kenneth E
AB - Abstract Institutions that conduct high-containment agricultural research involving domestic livestock represent a specialized category of programs that are accredited by AAALAC International. The accreditation process includes a comprehensive assessment of the overall program of animal care and use. However, the complex design of these facilities and the unique care required for animals in this type of environment often mean that additional attention will be directed at areas regarded as higher risk when the programs are evaluated. Specific issues that may stimulate additional discussion and interest include animal housing practices, environmental conditions inside the facility, maintenance of procedure and support areas, methods for obtaining and safely transporting healthy research animals, strategies to minimize animal pain and distress, unusual protocol review challenges, and institutional policies relevant to personnel training and safety. These issues are further discussed to inform institutions of potential concerns that should be reviewed and assessed during internal preparations for accreditation visits by AAALAC site visit teams. AAALAC, accreditation, agriculture, animals, biohazard containment, high containment, research, welfare BACKGROUND In 1965, a group of esteemed veterinarians, scientists, and medical professionals established AAALAC as the world’s first independent third-party assessment system for the care and use of animals used in research activities. Visionary leaders recognized sound animal care is the foundation of excellent science and that the most progressive and meaningful advancements in animal health and well-being programs are achieved through an external peer-review process.1 Since that time, AAALAC has continued as a well-established voluntary accreditation system that is focused first and foremost on the conscientious and humane treatment of animals in science and medicine. Operated as a private nonprofit organization, AAALAC International is governed by a board of directors elected by delegates representing a diverse and impressive group of scientific associations, veterinary specialties, and patient advocacy groups. More than 1000 programs are currently accredited in 49 countries around the globe, including pharmaceutical and medical device companies, medical schools, land-grant universities, government agencies, and nonprofit organizations. The type and complexity of institutions continue to increase as the number of accredited units grows, and today they encompass programs with traditional laboratory animals, agricultural animals, wildlife, exotics, and a wide range of aquatic species.2 Over time, AAALAC International has gained recognition around the world as an organization that drives quality improvement in the life sciences. This area of research has yielded major medical advances and important scientific contributions that are valued by the public. The conscientious use of animals for some aspects of the discovery process is critical but also leads to concerns about their care and use. Participation in AAALAC’s accreditation program demonstrates that an institution has invested extra resources and effort to achieve the highest standards and offers clarity in the level of the organization’s commitment to these responsibilities. Accreditation is a global process that can be used to gauge the quality of partner programs, harmonize animal care and use practices around the world, and provide assurance to diverse stakeholders and the public that the care of animals is a priority. Although AAALAC International has a pivotal role in the continuous improvement of animal care, it is not a regulatory body and does not make or enforce regulations. The international regulatory framework that governs animal research is an independent process and constantly evolving. For that reason, AAALAC has implemented a performance-based assessment system that relies largely on 3 primary standards to harmonize the accreditation process and ensure a more uniform application of standards between different legal jurisdictions.3 These standards generally exceed the minimum regulatory requirements that are in effect and include the National Research Council’s Guide for the Care and Use of Laboratory Animals,4 the Federation of Animal Science Societies Guide for the Care and Use of Agricultural Animals in Research and Teaching,5 and the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes, Council of Europe.6 AAALAC has adopted additional guidance and reference resources to guide the assessment of biosafety and biocontainment practices relevant to animal care. In the United States, this includes the Centers for Disease Control and Prevention and National Institutes of Health (NIH) publication titled Biosafety in Microbiological and Biomedical Laboratories (BMBL). Appendix D of the BMBL has information specific to agricultural pathogen biosafety and includes information on biocontainment requirements for loose-housed animals in Animal Biosafety Level 3 Agriculture (ABSL-3-Ag) facilities as well as pathogens of veterinary significance.7 The NIH Office of Science Policy has also published the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules, which details biosafety and biocontainment practices needed to safely manage research involving the construction or handling of recombinant nucleic or synthetic acid molecules, including the creation and use of organisms and viruses containing recombinant or synthetic nucleic molecules. Compliance is mandatory for institutions that receive NIH funding for this type of research. At minimum, an Institutional Biosafety Committee must be established for local oversight to ensure that nonexempt research activities are conducted in accordance with all required safety practices and procedures.8 INSTITUTIONAL RESPONSIBILITIES FOR ANIMAL RESEARCH INVOLVING BIOLOGICAL HAZARDS Establishment of a properly constituted and trained Institutional Animal Care and Use Committee (IACUC) or equivalent Oversight Body (OB) is a common requirement in the 3 primary standards used by AAALAC. The IACUC/OB has full authority for ensuring the care and use of animals at the institution meets appropriate standards, with responsibilities that include reviewing and approving proposed animal use protocols and significant changes to approved protocols, conducting regular inspections of animal facilities and animal use areas, performing regular reviews of the animal program, and establishing mechanisms for reviewing institutional concerns involving the care and use of animals.4 The committee does not directly provide or manage daily care or oversee every experiment. However, its ongoing assessment of the quality of these activities provides core information necessary to judge the overall performance of the program and serves as the institution’s assurance that resources are being used effectively in the best interests of animal well-being and scientific quality. When inter-institutional collaborations take place, the IACUC/OB must ensure that appropriate oversight mechanisms are in place for any research conducted at another location. AAALAC International does not intervene in the establishment or conditions of these types of agreements. However, these relationships are considered during accreditation assessments, particularly when all or some components of a collaborating institution’s facilities and services are integral to the quality of the accredited unit’s animal care and use program. If animals owned by an accredited institution are housed in a separately managed and administered facility, there are expectations that the care provided is equivalent and meets accreditation standards. This condition is met if the second institution is also accredited. However, if the second institution is not accredited, elements used by the accredited program must be included as part of that program's accreditation assessment and included in the on-site evaluation.9 The IACUC/OB also assesses the impact of occupational safety and health issues on proposed animal research activities, although other committees and safety professionals are given formal authority to manage and oversee research that involves harmful chemicals, biological agents, radiological materials, and other hazards. Optimal solutions typically involve multidisciplinary teams capable of implementing cross-cutting strategies that align with relevant federal, state, and local regulatory requirements. They address the institution’s specific hazards, vulnerabilities, and needs. The intersection of these interests must be carefully managed, regardless of the oversight system that is implemented, and strike an equitable balance that protects the health and safety of staff and animals while promoting the highest level of animal welfare consistent with the successful achievement of research goals. AAALAC evaluates research safety, occupational safety, and health functions as they pertain to the institution’s animal care and use program, again using a performance-based assessment system to determine how well the various components engage and work together. This is a continuous process, and evidence of a well-coordinated and effective oversight system typically includes strong administrative support, adequate resources, clearly defined hazard identification criteria, a comprehensive risk assessment screening process, sound management and control procedures for work with hazardous materials and agents, and a work-specific training program. The net effect should be a coordinated effort across all disciplines that ensures every worker receives clear, consistent guidance and understands what is expected to comply with institutional policies and procedures. UNIQUE ASPECTS OF AGRICULTURAL RESEARCH Agricultural research utilizes animals of many different species, including livestock—such as cattle and swine, poultry—and aquaculture species like those found in commercial production facilities, as well as wildlife. Pathogens and pests (eg, flies, ticks, mosquitos, etc) that affect these animals often have significant economic and environmental consequences, and many of these pathogens and pests have the potential to affect a wide range of hosts. Their spread or transmission, especially into previously uninfected populations, can negatively impact agricultural trade and will have a long and lasting effect on local or regional movement of commodities. For this reason, effective biosafety and biocontainment strategies must be implemented whenever high-consequence, exotic, or otherwise regulated biological agents (as defined in 9 § 12110 and 9 § 122.211) are used in research activities involving agricultural animals. In biomedical research, the term “biosecurity” describes measures that are implemented to protect infectious agents and toxins from loss, theft, escape, or misuse. The focus is on physical barriers and other practices that are used to limit laboratory access to these materials to authorized personnel.12 The Terrestrial Animal Health Code, published by the World Organisation for Animal Health, defines biosecurity for agricultural programs as a set of management and physical measures designed to reduce the risk of introduction, establishment, and spread of animal diseases, infections, or infestations to, from, and within an animal population.13 The World Organisation for Animal Health definition also applies to biosecurity programs implemented for agricultural animal research, except when regulated agents are involved that require added physical security. Biosecurity programs developed for agricultural applications must be rigorous and geared against the inadvertent, accidental, and/or intentional transmission or release of (1) pathogens, insects, parasites, and other pests capable of causing disease in animals or humans; (2) non-native species; or (3) genetically modified organisms that could threaten the health and productivity of animals, public health, or the environment. Hazards are managed through a hierarchy of controls that include facility design, engineering features, management practices, and personnel training. The appropriate level of containment is determined through a comprehensive risk assessment process that considers potential harm and consequences that would result, based on local incidence, transmissibility, host range, treatment and control options, and any regulatory or permit requirements. Most biocontainment classification systems correspond to the health-associated risks that may result from the work being performed. High containment and maximum containment refer to work with life-threatening agents transmitted by aerosol. In general, high containment is used to describe laboratories or facilities that operate at Biosafety Level 3 (BSL-3) conditions and involve agents for which a medical countermeasure is available. Laboratories and facilities operating at BSL-4 conditions are labeled as maximum containment and involve agents for which no vaccine or therapy is available, although some systems use high containment when referring to both BSL-3 and BSL-4 facilities.14 The species, size, and temperament of the animal model are critical factors that determine whether primary containment can be achieved at the cage level (ABSL 1–4) or must be accomplished through facility design features and management practices for animals that must be kept in open penning or other types of loose-housing inside the designated containment area (ABSL-Ag-3 and higher).4 Agricultural animals can adapt to a wide range of environmental conditions, which allows a variety of different housing options to be used in research for any given species. Studies intended to simulate conditions found in a modern agricultural production environment frequently adhere to animal husbandry standards and practices followed on a well-managed farm or ranch. Animals may be kept on open range, in fenced pens or pastures, or confined in traditional shelters (eg, barns, stables, pole sheds, etc) for production research. These housing systems are not compatible with high-biocontainment agricultural research, where the room perimeter or facility acts as the primary biocontainment barrier when animals must be housed in open pens (ie, loose housed) or noncontainment caging due to individual animal size or the number of animals within a group. These facilities must be specifically designed and operated to prevent the inadvertent release of agriculture-specific pests or pathogens into the environment or native animal populations. In a high-containment facility environment, animals are housed in a controlled vivarium where temperatures, air exchanges, and light cycles can be tightly regulated. Facility enclosure room walls, floors, pen walls, caging, or other equipment must all be constructed of materials that are nonporous, smooth, impervious, and durable enough to withstand repeated disinfection with chemicals and pressurized water or steam. Gates, barriers, or confinement chutes to restrain larger species must withstand being struck by hooves, heavy equipment, and other sharp objects. AAALAC expects that a site-specific risk assessment will be performed to guide facility operations that include waste-management procedures, ventilation system parameters, sanitation and disinfection methods, personal protective equipment (PPE) selection, and entry/exit protocols. Many aspects of facility design and operation are critical depending on the specific pest or pathogen being contained. Institutions should always consult with appropriate regulatory authorities and subject matter experts prior to initiating any work with a new agent and before starting any facility renovations or new construction to ensure the proposed changes will be appropriate for the intended uses. AAALAC considers that an effective training program is essential for ensuring research activities are conducted safely and with compassion for the animals. High-containment agricultural research programs demand that staff be proficient in performing biocontainment, biosecurity protocols, and complete species-specific training that enables them to work competently and safely with the animals that are housed. A variety of educational formats can be employed, ranging from live lectures, webinars, online courses, live demonstrations, mentoring, and attendance at professional conferences and seminars. Continuing education sessions should also be provided as refresher training when introducing new and improved techniques as they become available. OVERVIEW OF THE AAALAC ACCREDITATION PROCESS A pillar of the accreditation process is the on-site assessment of the animal care and use program. Planning for the on-site assessment involves a multi-tier approach that starts several months before the site visit takes place as the institution prepares and submits a comprehensive document referred to as the Program Description (PD) using the required template available on the AAALAC International website.15 The completed PD details the components of the institution’s animal care and use program, facilities, management, and oversight procedures and provides important information about its organization. The PD also serves as an orientation for the AAALAC representatives who are assigned to conduct the on-site evaluation. Another important benefit of the PD is that the preparation of this document serves as an opportunity for program personnel to conduct a detailed self-assessment of the entire program. In addition, many IACUCs/OBs use the PD to frame the periodic program review, an essential duty of the committee, with the side benefit of keeping the document current for future site visits. This fixed cycle of internal performance review eventually lays the groundwork for a systematic program of continuous quality improvement that drives innovation and progress. The accreditation process includes an evaluation of all species relevant to the institution’s research, teaching, or testing mission and may involve traditional laboratory animals, nonhuman primates, livestock, poultry, fish, wildlife, amphibians, and reptiles as well as a few unusual species (ie, cephalopods). The PD draws on AAALAC’s Rules of Accreditation for content. The Rules of Accreditation, established by the AAALAC International Board of Directors, underscore the value of sound animal husbandry principles regardless of species. The rules state that (1) animal care and oversight should be directed by qualified persons, (2) animal care personnel should be suitably trained and experienced, and (3) physical facilities and methods of animal care and use should permit their maintenance in a state of well-being and comfort.16 The content of the PD highlights various aspects of the care of animals, safety practices, and facility management that are pivotal to understanding the program’s organization, management systems, and operational procedures, serving as the framework for the on-site visit. Members of AAALAC’s Council on Accreditation (COA) conduct on-site assessments of accredited institutions at least every 3 years to ensure the program of animal care and use conforms with standards used by AAALAC drawn from the current scientific literature and consensus reports. The AAALAC International Executive Office assigns a current council member or council member emeritus to lead the site visit. That assignment is based on the right combination of knowledge, skills, and expertise to complement the institution’s animal research program. The council member is accompanied by 1 or more ad hoc consultants/specialists who also have skills and expertise tailored to the institution’s research program. A new site visit team is selected for each triennial visit to the institution to ensure every evaluation is independent and objective. In addition, language skills and knowledge of the country’s culture and regulatory framework are also considered when the site visit team is constructed. Additional information about the institution’s animal care and use program is gathered while the site visit team interacts with program personnel during the visit. During these discussions, the site visit team can ask questions, review additional documents, and tour facilities to gain a better understanding of how the program operates. Site visitors converse directly with scientists, occupational health and safety (OHS) personnel, caretakers, and veterinary staff to learn how internal policies are established and put into practice throughout the animal care and use program. They then compare how these efforts measure up to the primary standards adopted by AAALAC and how well they are adhered to in the program. Institutions are briefed on the site visitors’ preliminary assessments at the end of the visit and encouraged to provide a formal response to any suggestions or potential deficiencies that have been identified. Collectively, this information serves as the basis for the COA’s deliberations. The COA reviews all applications and site visit reports to determine if accreditation should be awarded, withheld, or revoked. This review is focused on whether specific program outcomes have successfully achieved the desired performance standards. The COA formally votes on each institution’s accreditation status, with affirmation by the board of directors before the decision becomes final. The various categories of accreditation are described on the AAALAC website.17 Importantly, accreditation can be revoked for due cause at any time following notification by the COA. In general, an institution with significant nonconformance with AAALAC’s standards would be placed on probationary status and given an opportunity to correct the deficiencies within a specified timeframe (not to exceed 12 months) before revocation becomes final. A site revisit is conducted to confirm all deficiencies have been satisfactorily resolved, and a second probationary period can be implemented if additional deficiencies are identified at that time. In some cases, accreditation is revoked without first placing the institution on probation. For new applicants, the COA also has the option to grant provisional status for up to 24 months when conditions warrant.13 AREAS OF SPECIAL INTEREST TO AAALAC High-containment agricultural research programs seeking accreditation must go through the same process as traditional research programs. However, due to the unique combination of highly specialized facilities and OHS concerns, some aspects of the program may receive added scrutiny during the assessment process. Common themes relevant to facility management, veterinary care, research oversight, and institutional policies are presented to illustrate some of the typical issues that may be of interest during an AAALAC site visit. Facility Management Program staff should serve as guides for the AAALAC site visit team as they tour the facility, following the facility’s biosecurity procedures and all PPE requirements. Site visitors should be made aware during the early planning stages, before the site visit is scheduled, if there are any special entry requirements (eg, vaccinations, respirator fit testing, animal contact restrictions, etc) that must be completed in advance to be able to enter the facility. The cleanest areas of the facility, such as the clean side of cage wash and survival surgery, should be entered first and contaminated areas, such as necropsy and the dirty side of cage wash, visited last. Areas housing young, unvaccinated animals should be visited before those housing older, mature animals to minimize cross-contamination between groups with different immune or health status. Containment areas used for studies with biological agents or other restricted areas must be clearly designated, with entrances posted with the names of agent(s) or type of research hazard(s) present, special entry requirements or procedures that must be followed to enter, and emergency contact information. Animal Housing AAALAC site visitors will be interested in seeing the diversity and capabilities of animal housing and procedure areas that are used for routine and high-containment research. This includes areas outside the primary animal enclosure (eg, barn, paddock, pond, etc), such as laboratories where animals may be transported for procedures or housed for varying lengths of time with the IACUC/OB approval. The site visitors will inquire how animals are transported to these areas, what types of procedures are performed, and who provides their care. Records and documentation while animals are in these areas are important to confirm that IACUC-/OB-approved procedures are being followed and that the animal care provided is equivalent to standards maintained consistently across the program. Social species of animals should be housed in compatible groups unless individual housing has been scientifically justified and approved by the IACUC/OB or authorized by a veterinarian for medical or behavioral reasons. The housing density should allow all animals to easily access sources of food and water and to perform natural behaviors without excessive competition. The site visitors may inquire how stocking density is adjusted if immature animals are housed together for extended periods of time. In some cases, animals in a high-containment environment may be housed individually to allow better observation of a certain animal’s food intake or when the size of the pen is limited. The site visitors will be interested in seeing how the IACUC/OB manages to address both the animal’s social needs and research objectives in these situations. The environmental enrichment program may be one option for alleviating potential stress associated with extended confinement and/or single housing. Every animal should have a clean, comfortable resting space within the primary enclosure but should also be able to easily stand and make natural postural adjustments without stepping on or injuring other animals in the group or itself. The flooring surface should provide good traction, and any bedding that is used should be compatible with drains and waste disposal systems. All surfaces within an animal enclosure must be free of rough or sharp edges, pinch points, and openings or gaps that could cut, injure, or entrap animals or workers. Other pieces of heavy equipment (eg, transport carts, head gates, restraint chutes, mobile tilt tables, scales, etc) must also be well maintained to facilitate the humane handling and movement of sick or moribund animals. Working parts should be kept lubricated to ensure smooth and safe operation, and surfaces must be kept smooth and free of defects to enable the entire unit to be cleaned and disinfected between uses. Most site visitors will want to know how the husbandry staff validates the effectiveness of sanitation methods used for equipment that must be cleaned in place or by hand, particularly if surfaces can become contaminated with pathogens, animal waste, or biological fluids under containment protocols. Surface defects, cracks, wall penetrations, and ledges must be repaired and sealed or protected to prevent entry and eliminate gathering points for pests, vermin, or biologicals (eg, insects, rodents, wild birds, organic materials, etc). An effective surveillance program is particularly important when arthropod vectors are reared in the laboratory for research or used for studies with large animals that are housed in pens or open caging inside the containment area. Facility Environment Environmental conditions inside the facility are also important. A required appendix to the PD is a recent facility heating, ventilation, and air conditioning system report, and the site visit team will review this data to make sure it is appropriate for each room’s intended use. The temperature, relative humidity, and ventilation or air exchange rate should provide maximum comfort and air quality for the age and type of animal housed in addition to being safe and appropriate for the types of procedures that are performed. Attention to environmental conditions is particularly important in a high-containment facility, which must be kept continuously under negative pressure. Pressure differentials must be designed so that air always moves from low-hazard areas to higher-hazard areas. The site visit team may ask about air handling systems that serve the containment area and what types of procedures are used to alert facility staff if environmental parameters start to drift outside the acceptable range. Additional discussion may evolve around the institution’s preventative maintenance program to ensure the integrity of critical equipment, including seals, filters, dampers, and other moving parts. Provisions for crucial repairs and emergency power in the event of power outages must be available and tested frequently to ensure steady, uninterrupted service. Insects, vermin, and other wild animals present significant risks to the health and welfare of research animals. An effective surveillance and control strategy is a critical element of the facility biosecurity program and should include routine monitoring of high activity areas, such as loading and receiving docks, feed/bedding storage areas, and animal housing rooms. Pesticide and rodenticide use should be closely coordinated with the veterinary staff and scientists to minimize any unintended effects on animal health or research data. Procedure and Support Areas Based on information provided in the PD and described in other program documents, the site visitors may also expect to see other areas and equipment that are needed to support research activities, such as imaging suites, surgical facilities, necropsy rooms, and feed storage areas. Programs that maintain livestock for research may use open sheds and barns away from the main facility to store hay and other commodities. These structures can attract birds and wildlife, and site visitors may ask what type of pest control methods are used to prevent contamination of stored animal feed and hay supplies or if any recent rodent or wildlife activity has been observed/documented in these areas. As the AAALAC representatives evaluate the facilities, special attention is given to equipment used to humanely transport large animals that are moribund or anesthetized to procedure areas under biological containment, such as carts, chutes, tilt tables, and hoist systems. AAALAC will verify that staff understands how to operate this equipment safely and the indications and restrictions on their use. Any equipment that requires routine calibration or testing, such as anesthesia machines, scales, autoclaves, biosafety cabinets, emergency eye washes, and fire extinguishers, should have maintenance logs or decals that show the equipment has been certified and is in good working order. Site visitors may ask for verification that surveys for waste anesthetic gases have been conducted and appropriate PPE is available for workers who use liquid nitrogen tanks or autoclaves, especially when local policies or procedures require the use of specific PPE. In these specialized areas, the need for emergency power typically extends to critical equipment such as biosafety cabinets, freezers, light sources, alarms, communication systems, and other electronic equipment. Generally, the AAALAC site visit team will review the institutional disaster plan to ensure that it includes provisions for continuity of routine animal care during extended power disruptions and other types of events that could interfere with normal services and potentially have a detrimental effect on animal health or welfare. The AAALAC site visitors will frequently review inventories and other records kept in animal procedure and storage rooms and investigator’s laboratories where animal procedures take place. Perishable items, such as animal feeds and pharmaceuticals, should be monitored for expiration dates. Materials that are sensitive to heat or cold should be stored in temperature-controlled areas and properly separated from incompatible items to prevent cross-contamination. For example, cold storage used for diets should not be used for chemicals, carcasses, and other waste materials. Controlled substances regulated by the US Drug Enforcement Agency must be stored in a secure area and their use closely monitored and documented. VETERINARY CARE Optimal health and welfare of research animals is the cornerstone of humane and reproducible science, and veterinarians serve an essential role by promoting the conscientious care and responsible use of animals within the research environment. The best results are always achieved by balancing scientific interests with the well-being of research animals. As subject matter experts, veterinarians are integral to this process and assist scientists in all aspects of experimental design, conduct, oversight, analysis, and interpretation. Animal Acquisition Many agricultural animals used in research, teaching, or testing originate from institutional herds or flocks or can be purchased from various sources, such as commercial breeders, hatcheries, and neighboring institutions. Some Class A commercial dealers are available, which can provide certain types of agricultural animals that have been purpose-bred in a closed or stable colony and raised for research purposes at a dedicated corporate facility. However, under most circumstances, animals are acquired from production herds and flocks that also supply industry. The genetics and health information for animals from both of these sources can usually be verified through herd or flock health records and diagnostic testing at the facility of origin prior to transfer. Animals acquired through random sources will often have inconsistent or unknown health status. Mixing animals from different backgrounds, along with the added stress of transport, can lead to disease outbreaks unless special precautions are taken to quarantine new additions until they are appropriately acclimated and conditioned to their new environment. A robust preventative health program is a fundamental component of veterinary care and should include strict health screening and quarantine requirements for all newly received animals to minimize the inadvertent introduction of new diseases. At minimum, there should be a process for receiving new animals that addresses any potential biosecurity concerns associated with the source of origin or potential exposure to pathogens during transport. New arrivals may need to be kept in isolation at a remote location physically distinct from the primary facility, and staff providing care may need to follow rigid biosecurity protocols to ensure there are no opportunities for cross-contamination between animal groups. In addition to live animals, this also includes thorough screening of fertile eggs, embryos, semen, and other germplasm used in reproductive programs. The temperament of newly received animals should also be carefully evaluated during the quarantine period to make sure every animal is successfully acclimating to its new surroundings and can be handled safely within the controlled environment of a high-containment facility. Animal Transport Many institutions rely on commercial vendors to haul agricultural animals and other types of supplies (eg, feed, bedding, etc) to and from their facility. Vehicles and other transportation equipment pose a high biosecurity risk, and it is important to make sure that all vehicles with access to areas inhabited by research animals meet appropriate sanitation standards prior to entry. Vendor vehicles that have been to other facilities with live animals (ie, livestock, poultry, etc) should be inspected at a designated area away from existing animal facilities, where animals can be safely off-loaded or the vehicle can be washed down and disinfected before gaining access to the main property. Facility-owned vehicles, loading ramps, and other transport equipment should also be well-maintained and disinfected between uses. It may be advantageous to assign specific vehicles and equipment, including tools and footwear, for exclusive use in high-containment areas. AAALAC site visitors will be interested in seeing facility-owned transport vehicles and learning how the IACUC/OB and veterinary staff coordinate these activities to ensure the health, safety, and biocontainment of animals that are transported, as well as the staff who perform these duties. Pain and Distress Management The IACUC/OB is charged with evaluating potential pain and distress that research animals may experience and routinely ensures that humane endpoints are incorporated into the study timeline to prevent, terminate, or relieve these negative experiences as quickly as possible without interfering in the successful achievement of the research objectives. Parameters such as general appearance, physiological variables, behavior, and production data have been successfully used to evaluate the overall health and condition of animals. However, recognition of pain and distress can be complex and challenging, particularly in many agricultural species that tend to be stoic and conceal signs of pain to avoid the appearance of vulnerability or weakness. Agricultural animals housed in groups also tend to aggregate, which can make accurate assessment of individual animals particularly challenging. Evaluation becomes even more complicated when animals are kept inside isolation chambers or must be observed through a viewing window or portal. AAALAC International expects institutions to make animal care and use decisions on the basis of regulatory and funding requirements, which are superimposed on a performance-based system that promotes and enhances animal welfare and quality science. For most programs, the best outcome is achieved when research personnel, veterinary staff, and the IACUC work cohesively together to develop and validate experimental endpoints that are consistent with the proposed research objectives and will ensure the optimal and humane care of research animals. This process proves especially valuable when humane endpoints are being developed for research involving unique pathogens or species and the expected outcomes cannot always be accurately predicted. The site visitors will be interested in learning how these various groups are involved in establishing humane endpoints that accurately correspond to an animal’s clinical condition and when the veterinary staff is consulted on strategies to manage and alleviate pain, including euthanasia if that becomes necessary. The AAALAC International website references several reports that offer guidance on the application of humane endpoints.18 Veterinarians should also be involved in training researchers and animal care staff to recognize humane endpoints and properly monitor animals for the onset of these critical indicators that initiate specific actions to maintain the animal’s comfort level. AAALAC International recognizes an institution’s obligation to customize the scope, content, and specific recordkeeping system implemented for the animal care and use training program. Therefore, in addition to ensuring any regulatory requirements for the training program are met, the site visitors focus their assessments on the institution’s success in meeting the research program’s training needs rather than the specific procedures or systems used. The end result should ensure all personnel who work with animals have appropriate training and experience to be able to perform their assigned duties safely and humanely. Depending on the program’s research needs, institutional personnel may be required to perform survival surgeries on agricultural animals. Veterinarians can provide valuable expertise by defining the optimal conditions and equipment needed for the species involved and the types of procedures performed. Appropriate facilities and trained staff are also needed to provide an adequate level of postoperative care, and veterinary input is required to minimize the development of complications that can compromise animal welfare and confound research results. Animal Disposition When a study is completed, veterinarians may be consulted for assistance during euthanasia and tissue harvest. Physical methods of euthanasia, such as captive bolt, may be preferred over injectable anesthetics to avoid residues that complicate tissue samples and the safe disposal of carcasses in larger species through rendering or composting. AAALAC site visitors will ask how the staff who euthanize agricultural animals are trained and, when the IACUC has approved physical methods, how the equipment is maintained to ensure it operates safely and properly. Whatever disposition method is used for research animals, it must always be approved by the IACUC/OB. In rare situations where animals can be used for other purposes or reassigned to other studies, veterinarians must verify their health status before they are transferred or reused. This may include proper observance of appropriate withdrawal times for any medications that were administered while the initial study was in progress. IACUC/OB OVERSIGHT One of the IACUC/OB’s essential roles is to review investigators’ credentials and experience and approve the institution’s proposed research activities that involve live animals. A successful outcome involves close coordination and communication between committee members, veterinarians, and the research team. Scientists understand that knowledge gained through animal research plays a pivotal role in science that is conducted to advance the health and welfare of humans and animals, and they acknowledge the unique responsibilities that accompany these privileges. High-quality data are anchored in animal care that is conscientious and compassionate, consistent with this collaborative approach. When the research involves agricultural animals housed in high-containment facilities, the committee may encounter complex issues that require balancing welfare considerations with scientific inquiry. The IACUC/OB must ensure the final study design includes clear, humane endpoints to minimize the level of pain and distress that animals experience and appropriate safeguards to protect personnel and animals outside of the containment facilities from research hazards. AAALAC site visitors will be interested in the strategies and processes that committee members have adopted to meet these responsibilities. For example, studies that involve exotic or high-consequence arthropod pests may require animals to be individually housed, housed in small enclosures, or even restrained to allow arthropods to attach and feed on the animal without being disturbed. The site visitors will likely seek information regarding what types of non-animal alternatives were considered, how animals are monitored and assessed for complications while arthropods are feeding, and measures that are taken to acclimate animals when prolonged restraint is proposed for a research purpose. On other occasions, agricultural animals may be fed restricted rations to limit their rate of growth or avoid excessive weight gain when normal maturation is expected to interfere with research goals. This can occur when an animal is surgically instrumented at a young age and the implanted device is expected to fail when the animal reaches a certain weight or size. Reducing the rate of growth may extend the length of time data can be collected from the same animal without significantly compromising animal health, thereby reducing the total number of animals needed to complete the study. The IACUC/OB is tasked with weighing the benefits the research is expected to yield against the potential detriments to the animal’s welfare and assessing whether this tradeoff is appropriate. A comprehensive review of potential interventions that would further minimize negative effects the animal experiences should be included as part of the committee’s analysis. The IACUC/OB is also responsible for reviewing adverse events, suspected noncompliance, and any other allegations relevant to the improper care or use of research animals. Establishing internal procedures for individuals to freely raise these issues without fear of discrimination or reprisal for their actions is inherent to the success of this form of self-regulation. Individuals who are unfamiliar with high-containment studies involving agricultural species may not fully appreciate all the measures that have to be taken to protect the welfare of these animals. Having a local mechanism for these concerns to be safely communicated and addressed in a fair and objective manner is critical for maintaining the public’s trust and confidence in the institution’s oversight system. The site visit team frequently discusses this topic with IACUC/OB members and program staff to better understand the types of challenges the institution faces. INSTITUTIONAL POLICIES Ultimately, the institution’s leadership has responsibility for ensuring adequate resources and support are available to maintain compliance and ensure the animal care and use program’s management successfully meets all relevant regulatory, scientific, and accreditation standards. To accomplish these goals, various organizational programs must be established to serve the needs of employees in terms of job-related training and OHS considerations. Effective training is a key element of a successful animal care and use program and should include mechanisms to verify all staff are competent at performing their assigned duties independently with minimal supervision. This is particularly important when duties involve farm animals or wildlife. At minimum, individuals assigned to work with these species should receive animal-specific training that covers the animals’ normal behavioral characteristics, effective handling practices, use of restraint equipment, and other physical safety precautions that need to be implemented. Experienced staff (eg, scientists, veterinarians, managers, etc) should be assigned as mentors to train and supervise new or less-experienced employees until their skill and competency levels can be confirmed. The scope and objectives of an OSH program must be customized to address the specific hazards and associated risks identified at the institution. Risk assessment is integral to this process and includes an evaluation of the dangers posed by research equipment, materials, procedures, animals, and the environment as well as the susceptibility of individual workers due to preexisting medical conditions, prior exposures, vaccination status, and other health restrictions. AAALAC site visitors may ask how various research hazards are evaluated and what types of actions have been implemented to address those that have been identified. Working with large animals in a confined environment introduces many opportunities for workers to be kicked, stepped on, pushed, or bitten. Some topics that may come up during AAALAC’s facility reviews include actions to protect workers from traumatic injuries that can result from the unpredictable behavior of large animals and while working with heavy or energized equipment (eg, heavy gates, restraint chutes, head locks, mobile tilt tables, ceiling hoists, wall-mounted drag systems, etc). There may also be concerns about sound levels in areas where loud equipment is operated or noisy species are housed (eg, roosters, pigs, etc). Depending on the results of the risk assessment that is performed, an institution may have a wide range of mitigation options available and should tailor the hazard control plan to meet the needs of the program. Interventions include elimination or substitution of hazards, installation of engineering controls, establishment of institutional safety policies and procedures, use of PPE, and effective worker training programs. CONCLUSIONS For more than 50 years, an institution’s accreditation by AAALAC International has been an acknowledgment of the research program’s commitment to excellence in animal care and use. The independent, third-party evaluation system has gained global respect as a rigorous and objective, performance-based process that offers a collaborative and constructive approach to continuous quality improvement while promoting the humane treatment of research animals. The specialized nature of high-containment facilities for agricultural research can generate challenging questions and concerns about the welfare of animals used in these studies. However, accreditation is a viable option for institutions engaged in this type of research and can serve as a powerful tool for maintaining the public’s confidence and trust in the level of care provided. Aspects of the program that may generate a high level of interest during the accreditation process include facility management practices, animal housing strategies, techniques for managing animal pain and distress, protocol review challenges, and institutional policies related to personnel training and safety. Institutions that conduct high-containment agricultural research with domestic livestock and are preparing for an upcoming AAALAC site visit may find this information useful as a benchmark for assessing the status of their own animal care and use program in these areas. 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TI - High-Containment Agriculture Animal Research: An AAALAC International Perspective
JF - ILAR Journal
DO - 10.1093/ilar/ilab006
DA - 2020-12-30
UR - https://www.deepdyve.com/lp/oxford-university-press/high-containment-agriculture-animal-research-an-aaalac-international-R5pFTJIvnT
SP - 10
EP - 17
VL - 61
IS - 1
DP - DeepDyve
ER -