Protecting Laboratory Animals
In scientific research, the use of animals is a necessity governed by strict regulations, which, however, vary from one country to another. How can practices be harmonized? The international AAALAC accreditation plays a key role in ensuring high standards and continuous improvement. Discover how legislation, the 3Rs principle, and AAALAC contribute to protecting research animals worldwide.
International Regulations: Varied Practices Across Regions
Europe
In Europe, a directive must be adhered to by all EU member states (European parliament and of the council of 22 September 2010 on the protection of animals used for scientific purposes, 2010), and the rules have been transposed into the respective laws of each member country.
United States
In the United States, two regulations govern the use of animals depending on the type of funding (public or private) for research (U.S. Department of Health and Human Services & National Institute of Health, 2015; U.S. Government Information, 1966).
In the United States, a law governs the use of animals: the Animal Welfare Act (U.S. Government Information, 1966). This law is supplemented by guidelines, one of which is general: ‘Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals’ (U.S. Department of Health and Human Services & National Institute of Health, 2015); research organizations may also impose strict rules to grant funding (see Comparative example: European and American legislation).
Asia
In Asia, each country has its own regulations, such as the ‘Law for the Humane Treatment and Management of Animals’ in Japan (Ministry of the Environment of Japan, 1973).
➔ These different regulations can lead to varying levels of consideration for animal welfare, ethics, the 3Rs (Replacement, Reduction, Reffinement), and transparency.
AAALAC accreditation: A global benchmark for laboratory animal care quality
A rigorous and voluntary accreditation process
AAALAC is a private, non-profit international organization headquartered in the USA. It will celebrate its 60th anniversary in 2025. International standards for the use of animals have been established, based on the strictest legislations and guidelines. AAALAC accreditation is based on 3 primary references: Guide for the care and use of laboratory animals (Committee for the Update of the Guide for the Care and Use of Laboratory Animals et al., 2011), Guide for the care and use of agricultural animals in research and teaching (Tucker et al., 2020), and appendix A of the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes (ETS NO. 123) (Council of Europe, 1986, 2006).
User establishments that wish to demonstrate their commitment to the responsible use of animals can apply for accreditation, which is granted only if AAALAC’s criteria are met.
Accreditation requests are voluntary, and establishments must provide a document outlining their animal care and use policy (PD for “program description”). Evaluators review this document and form their own opinion through a visit to the premises. This visit and document review lead to a report, which is then evaluated by the entire accreditation council to determine whether or not to grant AAALAC accreditation. Currently, around 1,100 research centers in 50 countries are accredited.
This accreditation must be renewed every 3 years. To obtain or maintain it, the user establishment must demonstrate alignment between its practices and the applicable standards, as well as a genuine commitment to continuous improvement.
Program descriptions according to the regions
Legislations may differ between countries, and therefore, AAALAC’s requirements may also vary. Three versions of the program description are available: a standard version, a version specific to Europe, and a version specific to Thailand.
The European-specific program requires the description of three additional elements beyond the standard program:
- The training manager
- The retrospective evaluation process
- The severity classes
The Thai program is similar to the standard program. The only difference being minor and related to the description of the list of equipment used for cleaning cages: autoclaves are not listed as an example in the Thai version.
The conditions for AAALAC accreditation:
AAALAC requires an active program for the care and use of animals. This program must include description of animals, facilities and equipment; professional, technical, and administrative support; policies and programs related to institutional responsibilities; veterinary care; protection of individuals (occupational medicine, hygiene, health, and safety). Furthermore, for a research unit to be accredited, it must demonstrate a reasonable level of activity relative to the available space for the housing and using animals.
At the end of the visit, AAALAC highlights the positive aspects and deviations from the standards. For the latter, two main categories of criteria are evaluated by AAALAC:
- The “must”: If these points are not met, the institution will not receive its accreditation.
- The “should”: These are considered suggestions for improvement. They are actions to be implemented before the next audit. Failure to comply with these points will not lead to immediate rejection of accreditation but may result in its withdrawal if they are not addressed in the following years.
What is required to be accredited?
The ‘must’: compliance with national regulations
To obtain AAALAC accreditation, establishments must comply with the legislation applicable in their country and the essential AAALAC standards, including the Guide for the care and use of laboratory animals (Committee for the Update of the Guide for the Care and Use of Laboratory Animals et al., 2011). These criteria, known as ‘musts,’ ensure a minimum standard of compliance.
Comparative example: European and American legislation
As an example, a comparison of European and American legislation was conducted.
- In Europe, Directive 2010-63-EU is applied (European parliament and of the council of 22 September 2010 on the protection of animals used for scientific purposes, 2010). Each country transposes this directive into its laws. The French translation was made in 2013 through a decree and five orders (see Regulations – Gircor).
This directive protects vertebrates and cephalopods (as well as their fetal forms from the third trimester of gestation) used for scientific and regulatory purposes, based on a pain/suffering threshold defined by the insertion of a needle carried out according to good veterinary practices. - In the USA, a law and guidelines protect animals used for scientific purposes:
- Animal Welfare Act (AWA) (U.S. Government Information, 1966): This federal law, dating from 1966, protects vertebrates used for scientific purposes, with two exceptions: mice and rats.
- Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals (U.S. Department of Health and Human Services & National Institute of Health, 2015) : These guidelines were first published in 1971 by the National Institutes of Health (NIH) and have been revised several times, with the current version dating from 1986. This document only applies to animals used in projects funded by public institutions (e.g., National Institutes of Health (NIH); Centers for Disease Control and Prevention (CDC); Food and Drug Administration (FDA)). All vertebrates are protected, including their fetal form, following the same principles as the European directive. Research organizations may also impose strict rules. For example, the NIH relies on OLAW (Office of Laboratory Animal Welfare) and its “Institutional Animal Care and Use Committee Guidebook.”
Thus, the same principles of animal protection used for scientific purposes are applied in Europe and the USA, but only Europe protects cephalopods and all vertebrates in private research.
This “protection” involves obligations to respect the sensitivity and needs of animals and requires tracking their use.
Whether in Europe or the USA:
- Facilities using animals are inspected
- Research protocols must be approved by ethical committees
- The 3Rs principle must be applied
- Staff must be trained
- Animal welfare committees monitor practices within the facilities
- The severity of procedures must be assessed
- The number of animals used must be reported
These are all the elements that AAALAC verifies; if a major point is not complied with, accreditation cannot be granted until it is resolved.
From a global perspective, European and U.S. legislations are similar. The differences appear in the more or less strict nature of inspections, evaluations, eligible training, or the precision of the reported data: European legislation is stricter.
The regulation on the minimum cage size for mice is a good example. In Europe, a minimum height of 20 cm must be respected, and the floor area will depend on the weight, number, and status of the animals; in the USA, the PHS Policy relies on the Guide for the Care and Use of Laboratory Animals, which simply states that animals must be housed in an adequate space (Committee for the Update of the Guide for the Care and Use of Laboratory Animals et al., 2011; U.S. Department of Health and Human Services & National Institute of Health, 2015).
Improving Beyond Regulatory Requirements: the ‘should’
A continuous improvement approach
These are the ‘should,’ which can be considered as goals to strive for.
Renewing accreditation requires demonstrating improvement between two inspections.
A concrete example: TransCure bioServices
During an inspection visit, AAALAC highlights areas for improvement. The audited facility can use these recommendations to enhance its animal care and use program. These improvements can relate to the 3Rs, but also to the management of the animal facility, staff protection, the organization of structures like the Animal Welfare Committee (AWC) or the ethics committee, retrospective data analysis, etc.
TransCure bioServices was able to follow the recommendations from AAALAC received in 2022 and even go beyond them. For example, improvements that have a direct impact on animals and help comply with the 3Rs are:
- Refinement of procedures: retro-orbital blood sampling replaced by other sampling methods; modification of the intracardiac sampling procedure
- Refinement of housing conditions: reduction of the maximum number of mice per cage; use of sustainable enrichment; provision of treats
- Reduction in the number of animals used: replacement of sentinel mice with an exhaust air collection system from cages
- Modification of pain management: more systematic use of analgesics; mandatory analgesia for mice with ulcerating tumors
- Addition of threshold points: tumor ulceration
Other improvements concern the more general functioning of the facility, for example:
- Staff protection: modification of personal protective equipment (PPE); exposure measures
- Organization of the animal welfare structure: improvement of audit management (also for the quality service), continuous training, and the decision-making process on animal welfare issues
- Data tracking: refinement of retrospective analysis
- Risk management: improvement of the business continuity plan
- Environmental protection: improved waste management
Towards a culture of care and excellence
Continuous improvement and the promotion of a culture of care are essential to earn AAALAC accreditation and to meet the requirement and spirit of the European directive and various recommendations on the use of animals for scientific purposes.
Committee for the Update of the Guide for the Care and Use of Laboratory Animals, Institute for Laboratory Animal Research, Division on Earth and LifeStudies, & National Research Council. (2011). Guide for the Care and Use of Laboratory Animals: Eighth Edition. In National Research Council 2011 (Ed.), Guide for the Care and Use of Laboratory Animals (8th ed.). National Academies Press. https://doi.org/10.17226/12910
Council of Europe. (1986). European Convention for the Protection of Vertebrate Animals used for Experimental and Other Scientific Purposes.
Council of Europe. (2006). Appendix of the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes (ETS NO. 123).
European parliament and of the council of 22 September 2010 on the protection of animals used for scientific purposes. (2010). Directive 2010/63/EU.
Ministry of the Environment of Japan. (1973). Act on Welfare and Management of Animals.
Tucker, C. B. ., MacNeil, M. D. ., & Webster, A. B. . (2020). Guide for the care and use of agricultural animals in research and teaching. American Dairy Science Association, American Society of Animal Science, Poultry Science Association.
U.S. Department of Health and Human Services, & National Institute of Health. (2015). Public Health Service Policy on Humane Care and Use of Laboratory Animals.
U.S. Government Information. (1966). Animal Welfare Act.