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Journal Vol 46 (4)

Report on the ILAR International Workshop on the Development of Science-based Guidelines for Laboratory Animal Care

J. Zurlo

J. Zurlo, Ph.D., is Director of the Institute for Laboratory Animal Research, The National Academies, Washington, DC.

Presented at the meeting of the Federation of European Laboratory Animal Science Associations (FELASA), held June 2004 in Nantes, France. The proceedings from this workshop are available on the ILAR website (www.dels.nas.edu/ilar).

Summary

The Institute for Laboratory Animal Research of the National Academies hosted a meeting in November 2003 in Washington, DC, titled "International Workshop on the Development of Science-based Guidelines for Laboratory Animal Care." The purpose of the workshop was to bring together experts from around the world to assess the available scientific knowledge that can have an impact on the current and pending guidelines for laboratory animal care. Platform presentations focused on a variety of issues, from information exchange on mechanisms for the development of regulations across different countries and cultures, to data-based scientific studies on the effects of environmental enrichment on research outcomes. In the discussion sessions, participants were tasked with addressing the current scientific literature on the specific session topics; identifying gaps in the current knowledge in order to encourage future research endeavors; and assessing the effects of current and proposed regulations on facilities, research, and animal welfare. Participants had ample opportunities to share research outcomes and viewpoints in the multiple breakout sessions. Summaries of all breakout sessions were presented in the general session. On the final day of the workshop during the point/counterpoint session, a diverse group of speakers presented their cases for and against harmonization of standards. Although some of the speakers had serious reservations about harmonization, most of the panel members supported some form of harmonization. A positive outcome of the workshop was the opportunity for scientists and veterinarians from many countries to begin a dialogue with a goal of understanding the basis for the differences in regulatory approaches in laboratory animal care and the hope of continuing discussions on ways to work together toward some type of harmonization.

Key Words: harmonization; international workshop; science-based guidelines

Rationale and Goals for the Workshop

In November 2003, the Institute for Laboratory Animal Research (ILAR²) of the National Academies held a workshop in Washington, DC, to discuss the status of laboratory animal care guidelines in the United States and other countries. ILAR was established in 1952 as part of the National Research Council to develop and make available information related to the care and use of laboratory animals. ILAR's mission is to develop guidelines and disseminate information on the scientific, technological, and ethical use of animals and related biological resources in research, testing, and education. ILAR promotes high-quality, humane care of animals and the appropriate use of animals and alternatives. ILAR functions within the mission of the National Academies as an advisor to the federal government, the biomedical research community, and the public.

The concept for this workshop arose from the International Committee of ILAR Council, a group of experts that advises ILAR about its activities and future projects. Sensing a need to look at the process of regulating animal research in different countries, the International Committee proposed holding a workshop to examine current changes occurring in Europe with the revision of Appendix A of the Convention on Vertebrate Animals Used for Experimental and Other Scientific Purposes (ETS 123) (COE 1986), and how these changes might affect regulations in the United States. Because ILAR is the board through which the National Research Council publishes the Guide for the Care and Use of Laboratory Animals (the Guide²) (NRC 1996), and because the Guide is used as the basis for Public Health Service policy on the humane care and use of laboratory animals (PHS 2002), ILAR Council deemed it appropriate to examine the issue of revising the Guide in the context of international activities.

The Guide is intended to assist investigators in fulfilling their obligation to plan and conduct animal experiments in accord with the highest scientific, humane, and ethical principles. It has been translated into at least a dozen languages and is used throughout the world as the basis for accreditation by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC²). Recommendations in the Guide, last revised in 1996, are based on published data whenever possible. Ideally, in accordance with the principles of the National Academies, all recommendations in the Guide should be based on scientific evidence; however, in many cases, there are no published data on basic laboratory animal care. In the absence of published data, the ILAR committee that has revised each edition of the Guide, beginning in 1963, has consistently relied on scientific principles, expert opinion, and experience with proven methods and practices.

Therefore, given the current status of regulations in the United States and Europe, the Program Committee (Table 1) identified the following goals for the international workshop:

To compare differences in the process for regulation development among countries;
To examine specific conditions of laboratory animal care and identify gaps in current knowledge in order to encourage future research endeavors; and
To answer the question, Should we harmonize guidelines/standards?

International Differences in Regulation or Oversight of Laboratory Animals

To address the first goal, individuals from different organizations were invited to identify the issues on an international level. John Miller presented on behalf of AAALAC International, Wim de Leeuw on behalf of the Council of Europe, and Gilles Demers on behalf of the International Council for Laboratory Animal Science (ICLAS²). In the second part of this session, representatives from agencies in different countries or groups of countries reviewed their regulatory requirements: Nelson Garnett, for the Office of Laboratory Animal Welfare at the US National Institutes of Health; Chester Gipson, for the Animal and Plant Health Inspection Service at the US Department of Agriculture; Jonathan Richmond, for Europe in general; Naoko Kagiyama, for the Central Institute for Experimental Animals in Japan; Clement Gauthier, for the Canadian Council on Animal Care (CCAC²); and Paul Gilman, for the US Environmental Protection Agency. Examples of points that summarize this session include the following:

Regulatory processes are highly variable based on culture and public influence.
Processes can range from multiple oversight and/or regulations to self-regulation.
The presentations encouraged better understanding of differences among participants.

Identification of Knowledge Gaps

The major portion of the workshop was dedicated to examining specific conditions of laboratory animal care and identifying gaps in current knowledge. Each of the next four sessions addressed various aspects of husbandry for laboratory animals. The species included in the discussions were those most commonly used in laboratories—rats, mice, rabbits, dogs, cats, and nonhuman primates. Topics included methods for evaluating housing needs and development of standards; environmental controls, (e.g., lighting, noise, ventilation) and their effects on animal homeostasis; and environmental enrichment. After three of the sessions, participants broke out into smaller groups for more focused discussions. Session leaders presented questions to their groups to center the discussion on identifying gaps in the scientific literature to support the development of guidelines or regulations. Rapporteurs recorded the discussions and presented summaries to the whole group after each breakout session.

Although the entire workshop cannot be summarized here, several major outcomes related to the goal of identifying gaps in information merit mention. It was uniformly agreed that more scientifically based studies are needed to determine the optimal conditions for each species of laboratory animals, including cage sizes, environmental enrichment, lighting, temperature, humidity, and air changes, as examples. Participants expressed different opinions about changing guidelines and standards. Some felt that public pressure forced change in the absence of data, resulting in more reliance on expert opinion; whereas others felt that guidelines should be changed only when scientific data are available. In general, differences were largely geographical or cultural. Most participants agreed that guidelines must be beneficial to the animals and support good science. Many also agreed that guidelines are not productive or practical when they mandate specific conditions, but they should provide minimum standards. Data were presented showing that even when environmental conditions were standardized, there can be variability in experimental outcome due to differences in animal handlers. Other data showed that environmental enrichment can affect numerous anatomical and physiological parameters. This type of information shows that there are many unanswered questions regarding the scientific basis of animal care.

Discussion on Harmonization

The final session of the workshop was a point/counterpoint discussion about harmonization of guidelines. Ten individuals from various countries and institutions made brief statements that supported harmonization to some degree, or did not support it. In Table 2, the individuals who participated in the panel are listed. A key point of discussion was the definition of "harmonization." Distinctions were drawn between harmonization versus standardization, guidelines versus regulation, and performance versus engineering standards.

Arguments against harmonization included the following:

There are still too many gaps in the science to support harmonization.
There are too many differences among countries (e.g., culture, tradition, values, laws, regulations, and religious beliefs).
Harmonization would pose limitations in the environmental range of experimental study and in the process mask important biological effects

The process of harmonization should include the following steps:

Consider harmonized practices, rather than regulations—ethical review, animal care and use review, and national oversight authority.
Begin by exchanging opinions and thoughts.
Strive for harmonization of guidelines, rather than standardization.

Guidelines should

Provide clear benefits to the animals;
Not interfere with research;
Be based on science; and
Be published and used as reference tools.
Allow flexibility for
- Best context-specific arrangements required to promote animal welfare and good science;
- Innovation to challenge and increase standards continuously; and
- Changes in guidelines as more scientific evidence becomes available.
Refer to the Principles of the Council for International Organizations of Medical Sciences (CIOMS²)—International Guiding Principles for Biomedical Research Involving Animals (CIOMS 1985); (www.cioms .ch/1985_texts_of_guidelines.htm).
Use the US Government Principles (IRAC 1983); http://www.nal.usda.gov/awic/pubs/IACUC/vert.htm

Future Directions

Participants in the final discussion offered many valuable suggestions for future steps, including the following:

Identify specific research problems that need addressing, and organize an effort in multiple laboratories to generate publishable data (e.g., optimal enclosure dimensions, best caging material, environmental enrichment, euthanasia practices, and ventilation requirements).
Form a consortium to coordinate research needs, funding, and efforts in identified areas.
Make an effort to collect data that have already been generated, but not reported.
Encourage investigators to include more information about husbandry and experimental manipulations of animals in research papers.
Make scientists more aware of the consequences of laboratory animal care.
Harmonize education and training initiatives.
Hold future meetings with fewer participants to continue and facilitate further dialogue, outline steps for future initiatives, and agree on common goals.

Acknowledgments

ILAR acknowledges support for this workshop from the following: US National Institutes of Health (Office of Laboratory Animal Welfare and the National Center for Research Resources); AAALAC International; CCAC; Centre for Best Practice for Animals in Research (now the National Centre for the Replacement, Refinement and Reduction of Animals in Research) at the Medical Research Council, UK; Federation of European Laboratory Animal Science Associations; ICLAS; and Laboratory Animals, Ltd.

Abbreviations used in this Report: AAALAC, Association for Assessment and Accreditation of Laboratory Animal Care International; CCAC, Canadian Council on Animal Care; Guide, Guide for the Care and Use of Laboratory Animals; ICLAS, International Council for Laboratory Animal Science; ILAR, Institute for Laboratory Animal Research.

References

CIOMS [Council for International Organizations of Medical Sciences]. 1985. International Guiding Principles for Biomedical Research Involving Animals. Available online (www.cioms.ch/1985_texts_of _guidelines.htm).

COE [Council of Europe]. 1986. European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes (ETS 123). Strasbourg: Council of Europe.

IRAC [Interagency Research Animal Committee]. 1985. US Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training. Available online (http://www .nal.usda.gov/awic/pubs/IACUC/vert.htm).

NRC [National Research Council]. 1996. Guide for the Care and Use of Laboratory Animals. 7th ed. Washington, DC: National Academy Press.

PHS [Public Health Service]. 2002. Public Health Service Policy on Humane Care and Use of Laboratory Animals. US Department of Health and Human Services Public Law 99-158, Health Research Extension Act of 1985. Washington DC: DHHS. Available online (http://grants.nih.gov/grants/olaw/references/phspol.htm)