Resource
Approaches to animal research project evaluation in Europe after implementation of Directive 2010/63/EU Javier Guillén, DVM1, Sally Robinson, PhD2, Thierry Decelle, DVM, DipVetLAS3, Cornelia Exner, PhD4 & Martje Fentener van Vlissingen, DVM, PhD, DipECLAM5
© 2015 Nature America, Inc. All rights reserved.
Directive 2010/63/EU requires the evaluation and authorization of all research projects and training activities involving the use of animals and defines some components and expertise necessary for the evaluation process. Adoption of Directive 2010/63/EU provided an opportunity to harmonize project evaluation processes across Europe, but thus far, member states have used a variety of approaches in the transposition and implementation of Directive 2010/63/EU. The authors discuss and compare the project evaluation systems being implemented in five European Union member states (France, Germany, Spain, the Netherlands and the UK).
npg
Prior to 2010, research using animals in European Union (EU) member states was guided by Directive 86/609/EEC1, which did not require evaluation of animal research proposals. Several countries did have national regulations that included this requirement, however, and ethical evaluation was done at some establishments in other countries for reasons such as institutional commitment, good practice and funding or accreditation requirements. The evaluation systems in place differed with respect to the composition of evaluation committees; the type of information provided; the factors considered during the evaluation; the training of participants; and the participation of institutional, external and government bodies. A 2007 report by the Federation of European Laboratory Animal Science Associations (FELASA) illustrated the heterogeneity of project evaluation practices in Europe2 but also identified certain key elements included in all ethical evaluation processes and proposed a set of recommendations for appropriate ethical review2. In 2010, Directive 2010/63/EU3 came into force. It contains 59 introductory Recitals, 66 effective Articles and 8 Annexes (Table 1). Directive 2010/63/EU requires the evaluation and authorization of all research projects and training activities involving the use of animals. Its requirements for project evaluation include
the criteria that a project should meet; the components of the project evaluation, including a harm–benefit analysis; the expertise to be considered for the evaluation process; and the need for transparency. Directive 2010/63/EU also states that the evaluation shall be done in an impartial manner and may integrate the opinion of independent parties. Several bodies or persons have oversight functions under Directive 2010/63/EU that may or may not be directly involved in project evaluation (Table 2). First, the Competent Authority is the body designated by a member state to carry out the obligations arising from Directive 2010/63/EU. This is normally a national or regional government body. Second, the institutional Animal Welfare Body (AWB) has an advisory role in matters such as animal welfare, implementation of the principles of the 3Rs, follow-up of projects and rehoming schemes. Third, the person responsible for overseeing the welfare and care of the animals in the establishment or Animal Welfare Officer (AWO) must be a member of the AWB. Fourth, the national committee for the protection of animals used for scientific purposes has an advisory role to the Competent Authority and the AWBs. Finally, bodies other than public authorities can be designated by the Competent Authority for the implementation of specific tasks laid down in Directive 2010/63/EU.
1AAALAC International, Pamplona, Spain. 2AstraZeneca, Cheshire, UK. 3Sanofi Pasteur, Lyon, France. 4University of Marburg, Marburg, Germany. 5Erasmus MC, Rotterdam, the Netherlands. Correspondence should be addressed to J.G. ([email protected]).
LAB ANIMAL
Volume 44, No. 1 | JANUARY 2015 23
Resource
TABLE 1 | Contents of selected Articles and Annexes in Directive 2010/63/EU
npg
© 2015 Nature America, Inc. All rights reserved.
Article
Content
3
Definitions
6, Annex IV
Approved methods of humane killing (per species), exemptions for emergencies, research requirements for equally (or more) humane methods
19
Freeing and rehoming of animals to external parties at end of procedure
24
AWO tasks
26
AWB composition
27
AWB tasks
36–45, Annex VI
Procedures for granting, renewing, amending and withdrawing project licenses, including requirements for non-technical summaries and retrospective assessment
38
Procedures and criteria for ethical review of project license applications
49
National committees
55
Safeguard clauses for allowing exceptions (species, severity) where consent of Ethics Committees must be sought
59
Competent Authority and delegation of functions to other bodies
The adoption of Directive 2010/63/EU provided an opportunity to harmonize project evaluation practices across Europe. But member states have used various approaches to the transposition and implementation of Directive 2010/63/EU, resulting in variation in project evaluation processes among the member states. This variation may relate to the nature, roles, composition and expertise of the bodies responsible for project evaluation, which may affect the speed, flexibility and output of the evaluation process. In this article, we present, discuss and compare the approaches to project evaluation that have been implemented in
five EU member states: France, Germany, Spain, the Netherlands and the UK. RESPONSIBILITY FOR PROJECT EVALUATION Directive 2010/63/EU gives the responsibility for carrying out project evaluation to the Competent Authority, but it also allows member states to designate bodies other than public authorities for the implementation of specific tasks, including project evaluation. As a result, some member states allow the designation of AWBs and other institutional or external committees for project evaluation (Table 3).
TABLE 2 | Oversight functions defined in Directive 2010/63/EU and their roles in five EU member states Name; role Body or person
Level
France
Germany
Spain
The Netherlands
The UK
Competent Authority
National or regional
Regional inspectors; project authorization
Regional committees; project evaluation
Regional Competent Authorities; implementation and decisions
CCD; project authorization
Home Office Inspectorate; project evaluation
AWB
Institutional
Advisory
Advisory
Advisory
Advisory
Advisory
AWO
Institutional
General oversight
More authority than AWB
General oversight
General oversight
General oversight
National committee for the protection of animals used for scientific purposes
National
Advisory
Advisory
Advisory
Advisory
ASC; advisory
Other designated bodies
Institutional or external
Ethics Committee designated for project evaluation
Institutional AWBs or external authorized bodies designated for project evaluation
Institutional or external review bodies designated for project evaluation
24 Volume 44, No. 1 | JANUARY 2015
www.labanimal.com
Resource
TABLE 3 | Project evaluation and authorization processes in five EU member states France
Germany
Spain
Institutional Ethics Committees (independent from AWBs)
Competent Authority assisted by regional Ethics Committees
Institutional or external Authorized Bodies
Institutional or external ethics committees
Home Office Inspectorate and institutional AWERBs
Role of AWB in project evaluation
No
Yes
Yes
Yes
Yes
Composition of evaluation body
Scientist, technician, animal caretaker or person in charge of killing of animals, veterinarian and member not from the establishment
Per Article 38
Per Article 38 when the AWB is responsible: AWO, researcher(s) not involved in the project, and person with knowledge and expertise in animal welfare not related to the experiment and the user
Per Article 38 plus an expert on ethical review; majority of members should not be employed by the institution
For AWERB, at least one Named Animal Care and Welfare Officer, at least one Named Veterinary Surgeon and scientific member
Body responsible for project authorization
Ministry of Higher Education and Research
Regional Competent Authorities
Regional Competent Authorities
CCD
Secretary of State
Existence of national project application template
Yes
Yes
No
Yes
Yes
Body responsible for project
© 2015 Nature America, Inc. All rights reserved.
evaluation
npg
France In France, Directive 2010/63/EU was transposed as a Decree4 and its related Arrêté5 (an order with more detailed enforcement instructions coming from the Decree) as of 1 February 2013. Under these regulations, an establishment must set up two different oversight bodies that are independent but have complementary missions: the institutional Ethics Committee and the AWB. The Ethics Committee is responsible for project evaluation, whereas the AWB has advisory functions as described in Article 27 of Directive 2010/63/EU. One Ethics Committee can cover several establishments, but each establishment should have a specifically designated Ethics Committee, which must be registered with the Ministry of Research. Rules governing the function of Ethics Committees are defined in the regulations and in the National Charter on the Ethics of Animal Experimentation6, which was issued in 2009 by the National Ethical Committee on Animal Experimentation and needs to be updated in accordance with the new requirements of Directive 2010/63/EU. The charter includes some guidance on project evaluation with flexibility for adjustments in accordance with research programs and with the size and complexity of the establishment but does not define a specific deliberation or decision process, except in the case of a conflict of interest. The framework for project evaluation in LAB ANIMAL
The Netherlands
The UK
France is mainly derived from the Guide for the Ethical Evaluation of Experiments Using Laboratory Animals7 issued by Gircor, an association of professionals from French public and private research institutions, in 2009, before regulations required a formal review process. The Guide for the Ethical Evaluation of Experiments Using Laboratory Animals is widely used as a reference by the Ministry of Research, by Ethics Committees and by establishments in France and needs to be updated to reflect the requirements of the new regulations. Since 2008, training sessions have been carried out to ensure the competency of project evaluators and the coordination of evaluations. Annual audits are carried out to ensure compliance and include review by a regional representative of the Ministry of Research and inspection by the Ethics Committee. Veterinary inspectors also review animal use and the implementation of the principles of the 3Rs (reduction, replacement and refinement). Germany In Germany, Directive 2010/63/EU is transposed into the revised Animal Welfare Act, which took effect on 4 July 2013 (ref. 8). An ordinance9 that regulates the implementation in detail was also issued. These new regulations have not resulted in substantial changes to the parties responsible for project evaluation or to the evaluation process. Regional Ethics Committees Volume 44, No. 1 | JANUARY 2015 25
Resource
npg
© 2015 Nature America, Inc. All rights reserved.
composed of expert volunteers are responsible for project evaluation. The plausibility and ethics of project applications are reviewed and evaluated by an appropriate party (government body, veterinary authority or state ministry) as determined by the regional Ethics Committee. Pain, suffering and lasting harm caused to the animals are taken into account, and harm–benefit analyses are done. Implementation of Directive 2010/63/EU has made the process more complex and time-consuming, however. The definition of animal experiments has been expanded: for example, the breeding of altered transgenic lines is now permanently subject to authorization requirements, and experiments for the purpose of education, training and advanced training are now subject to more extensive review. Spain In Spain, transposition of Directive 2010/63/EU ended with the publication of Royal Decree 53/2013 (RD 53/2013; ref. 10). Under RD 53/2013, entities named Authorized Bodies carry out specific functions designated by the regional public competent authorities. Authorized Bodies are explicitly assigned to carry out project evaluation. Authorized Bodies are registered with the central government and can be used by registered establishments. Animal Welfare Bodies in user establishments may become Authorized Bodies. The criteria for the evaluation process to be used by Authorized Bodies are copied from Article 38 of Directive 2010/63/EU and include the concepts of transparency and impartiality. In line with Directive 2010/63/EU, RD 53/2013 emphasizes that Authorized Bodies must have the technical expertise and infrastructure necessary for the task and must operate without any conflicts of interest. The national committee for the protection of animals used for scientific purposes has no project evaluation functions but has the role of advisement and coordination. The Netherlands The Dutch government has chosen to adapt the current law on the protection of animals used for research (Animal Experiments Act11) to comply with Directive 2010/63/EU. The process of transposition is ongoing; it was overseen by the Ministry of Public Health through 2012 and by the Ministry of Economic Affairs (also responsible for agricultural policy and animal welfare) since January 2013. In 2013, the changes in the regulations were prepared for parliamentary approval. The House of Representatives approved the changes in December 2013, with some amendments; the Senate still has to vote on the changes (but is not allowed to amend the regulations, only to approve them or to redirect them to the government). The present law already requires ethical evaluation of the use of animals for research or training. Approximately 20 Animal Use Committees (AUCs) are responsible for project evaluation; 26 Volume 44, No. 1 | JANUARY 2015
these are formally recognized and mandated by the Minister. Most AUCs are institutional, some serve more than one establishment, and a few are independent. The workload of the different AUCs varies substantially (in terms of both number and diversity of project applications, which total more than 4,000 annually12), and some AUCs operate subcommittees. The process of project evaluation and licensing will be substantially different if the currently proposed changes come into force. Project evaluation will be split over three different levels of review, and establishment of the AWB will intensify internal evaluation. Draft applications for project licenses will be previewed by the AWB in view of local provisions, expertise and facilities. The AWB will take over the detailed technical evaluation in view of best practices and application of the principles of the 3Rs. Once a project has been licensed, the AWB will have a key advisory role in its execution. Ethical evaluation will be done by a recognized review body and then reviewed by the Competent Authority (Central Committee on Animal Experiments, CCD). This threelevel review process will partially dissociate technical and ethical review, creating better opportunities for ethical discussion, and should make procedures more consistent nationally. The new processes may present some challenges in view of efficiency and the meeting of deadlines. Furthermore, both the administrative burden and the costs of review procedures for projects and establishments will rise substantially. The UK In the UK, the use of animals in experiments and testing is regulated under the Animals (Scientific Procedures) Act 1986 (ASPA)13. ASPA has recently been revised to transpose Directive 2010/63/EU. The revised legislation came into force on 1 January 2013 (ref. 14). Standard project license applications are evaluated by two oversight bodies. The first evaluation by the Animal Welfare and Ethical Review Body (AWERB) allows for local knowledge, expertise, 3Rs principles and best practice to be discussed and incorporated. The new AWERBs, in most respects, continue and develop the work of the local Ethical Review Processes that they replaced on 1 January 2013. The second, formal project evaluation (including the harm–benefit analysis) is done by the Competent Authority (the Home Office Inspectorate) and relies on professional judgment, continuous professional development, knowledge–sharing, scientific literature precedents and external views (e.g., from the Animals in Science Committee (ASC) or other expert assessors). The ASC is an independent, public body set up under ASPA and responsible for providing impartial, balanced and objective advice to the Home Office. Certain project license applications may be referred to the ASC, including those that involve the use of wild-caught nonhuman primates; those that involve www.labanimal.com
Resource
the use of cats, dogs, equidae or nonhuman primates in severe procedures; those that involve the use of endangered species; and those that invoke any of the safeguard clauses (reasons for the Competent Authority to accept exceptions) in Directive 2010/63/EU with respect to the purpose of nonhuman primate use, proposals for the use of a great ape or proposals to cause long-lasting pain, suffering or distress that cannot be ameliorated.
npg
© 2015 Nature America, Inc. All rights reserved.
Comparison Some member states assign the responsibility for project evaluation to the Competent Authority, whereas others delegate this responsibility to institutional or external bodies. Pragmatism may form the basis of this decision for many member states, particularly those lacking sufficient and trained human resources to carry out appropriate project evaluation. Government bodies responsible for the control of animals in research might not have the resources to support this or might lack the personnel and expertise and might therefore rely on other, more specialized bodies for project evaluation. In these cases, it is important to consider whether the impartiality required by Directive 2010/63/EU can be assured by institutional bodies. Impartiality in a small institution might be hard to guarantee, particularly if there are only a few researchers, if they all work in the same field and if the institution depends on the rapid development of projects. It might be easier for a larger institution to establish a committee with a composition broad enough to minimize conflicts of interest. External independent parties, including committees belonging to larger institutions, can be incorporated into the project evaluation process in order to guarantee impartiality. In member states that assign the responsibility for project evaluation to the Competent Authority, such as Germany and the UK, preliminary evaluation at the institutional level is common, whereas in those that delegate this responsibility to institutional or external bodies, such as France, Spain and the Netherlands, project authorization by the Competent Authority after evaluation is common, allowing the Competent Authority to inspect the work of the designated bodies. In both cases, collaboration between institutional bodies and the Competent Authority is beneficial. ROLE OF AWB IN PROJECT EVALUATION The AWB is an institutional entity that, under Directive 2010/63/EU, has an advisory role on matters related to animal welfare, including the establishment and review of processes to monitor and report on these matters; on implementation of the 3Rs; on the development and outcome of projects; and on rehoming schemes. Directive 2010/63/EU does not assign project evaluation responsibility to the AWB, but in member states that delegate this responsibility to institutional bodies, it seems reasonable for AWBs to form the basis for these bodies, LAB ANIMAL
expanding their composition to fulfill the requirements for expertise and to guarantee impartiality. In practice, the involvement of AWBs in project evaluation varies among member states. France In France, the AWB is not involved in project evaluation but functions in an advisory role as described in Article 27 of Directive 2010/63/EU, acting at an institutional level with knowledge of resources, policies and procedures and ensuring the implementation of good practices regarding animal welfare and use and the principles of the 3Rs. Germany In Germany, institutional AWBs are not involved in project evaluation but function in an advisory role. Each AWB is chaired by an AWO, who initially discusses project applications with the applicants. The meeting minutes of the AWB may be reviewed by the Competent Authority responsible for project authorization. Spain In Spain, AWBs can be named Ethics Committees for Animal Experimentation and can be designated as Authorized Bodies when they comply with all the criteria for project evaluation. This is interpreted in some cases to allow institutional AWBs (or Ethics Committees) to evaluate institutional projects. This might seem to be a pragmatic solution because many of Spain’s Competent Authorities lack the resources and expertise for project evaluation, but it presents a potential conflict of interest. In regard to the issue of conflict of interest, RD 53/2013 refers to a Law from 1992 (Ley 30/1992; ref. 15) ruling on the functioning of public bodies, which strictly defines what constitutes such a conflict. On the basis of this law, some Competent Authorities do not allow institutional Authorized Bodies to evaluate projects at their own institutions, whereas others do as long as the members of the Authorized Body are not themselves involved in the proposed project. When impartiality of an institutional Authorized Body cannot be guaranteed, project evaluation may need to be done by an external Authorized Body. Use of an external Authorized Body could be problematic when it comes to retrospective assessment, which includes the evaluation of whether the objectives of the project were achieved; the harm inflicted to animals (number, species and severity); and the elements that may contribute to the further implementation of the principles of 3Rs and is required for all projects using nonhuman primates and all projects including procedures categorized as severe. The Netherlands Under the currently proposed regulations, AWBs in the Netherlands will have a broad role in project Volume 44, No. 1 | JANUARY 2015 27
Resource
npg
© 2015 Nature America, Inc. All rights reserved.
evaluation. Draft applications for project licenses will be previewed by the AWBs in view of local provisions, expertise and facilities available. Then, when the project license comes into use, the AWB will carry out detailed technical evaluation of single study protocols, applying approved strategies for minimizing severity and the number of animals used. The AWB will also advise on project development and carry out retrospective reporting. The UK In terms of project evaluation, the UK AWERB has an advisory role, providing guidance to each establishment’s license holder on whether to support project proposals, providing local expertise during the development of new license applications and identifying specific issues that need to be addressed. This role also enables the AWERB to fulfill the guidance of Article 27(1d) of Directive 2010/63/EU to “follow the development and outcome of projects”. The AWERB provides essential advice on animal welfare and scientific aspects of applications, including local and institutional standards. Comparison Comparing the different responsibilities of the AWB across countries shows that project evaluation is no longer the only task assigned to institutional review bodies. Other oversight and advisory functions are now assigned to AWBs, with the intention of creating a culture of care and promoting the application of the principles of the 3Rs. Specific functions may include advising on matters related to the welfare, acquisition, accommodation, care and use of animals; advising on the application of the principles of the 3Rs and relevant technical and scientific developments; establishing and reviewing internal operational processes such as monitoring, reporting and follow-up on matters involving the welfare of animals housed or used in the establishment; following the development and outcome of projects, including the effect on the animals used, and identifying elements that may enhance application of the principles of the 3Rs; and advising on rehoming schemes, including the appropriate socialization of the animals to be rehomed. It may be a matter for individual establishments to determine whether to add review functions to the tasks of the AWB when project evaluation is assigned to other bodies (e.g., Ethics Committees or government authorities) in order to ensure that project applications are well-prepared and conform to institutional policies. This has been done in many establishments across Europe even though there was no legal mandate to do so. AWOs, veterinarians or fully constituted institutional review bodies have been operating to ensure consistency and good practice in research proposals submitted to Competent Authorities. In cases 28 Volume 44, No. 1 | JANUARY 2015
where project evaluation responsibility is retained by the Competent Authority, the AWB can ensure that other activities are carried out. However, the emphasis of Directive 2010/63/EU on the advisory nature of the AWB’s functions may jeopardize its authority, depending on each institution’s level of commitment. COMPOSITION OF PROJECT EVALUATION BODIES Article 26 of Directive 2010/63/EU indicates that the AWB shall include at least the AWO and, in the case of user establishments, a scientific member. It shall also receive input from the designated veterinarian or the expert referred to in Article 25. But Directive 2010/63/EU does not indicate specific requirements for the composition of the body (Competent Authority) responsible for project evaluation. It indicates only that expertise in the following areas shall be considered: (i) the areas of scientific use for which animals will be used, including replacement, reduction and refinement in the respective areas; (ii) experimental design, including statistics, where appropriate; (iii) veterinary practice in laboratory animal science or wildlife veterinary practice, where appropriate; and (iv) animal husbandry and care. It indicates that the project evaluation process shall be transparent while safeguarding intellectual property and confidential information, shall be carried out in an impartial manner and may integrate the opinion of independent parties. These requirements allow variation in the composition of the project evaluation body while also necessitating that AWBs that have been assigned the responsibility for project evaluation function expand their composition to ensure transparency and impartiality. France French Ethics Committees responsible for project evaluation must include members representing five different functions: scientist, technician, animal caretaker or person in charge of killing of animals, veterinarian and lay member. Impartiality is guaranteed by national charter and law. Ethics Committee members sign a formal commitment to withdraw from the evaluation if any conflicts of interest are anticipated. Germany The members of the German Ethics Committees in charge of project evaluation come from research, industry and animal welfare organizations. The majority of them must have a basic academic education. Their work is done on a voluntary basis, and they report to the local authority responsible for project authorization. The AWOs and the local authorities are independent as required by the German Animal Welfare Act. Spain In Spain, where the new legislation allows AWBs to be authorized to carry out project evaluation, an authorized www.labanimal.com
Resource
AWB must comprise the AWO; researcher(s) not involved in the project; and a person with knowledge and expertise in animal welfare not related to the experiment and the establishment. The Netherlands The altered legislation in the Netherlands would maintain AUCs but adapt their composition to comply with Article 38 of Directive 2010/63/EU (fields of expertise) and maintain the provisions for freedom of conflict of interests.
npg
© 2015 Nature America, Inc. All rights reserved.
The UK The revised UK legislation specifies that the AWERB must have, as full members, at least one of the establishment’s Named Animal Care and Welfare Officers and at least one Named Veterinary Surgeon. For an establishment, the AWERB must also include a scientific member and should ensure that other named persons, including the Named Information Officer and the Named Training and Competency Officer, are actively engaged with the AWERB, as its tasks are far broader than local project evaluation. Establishment license holders should arrange for their AWERBs to actively seek a wider membership taking into account, in a transparent manner, the views of people who do not have responsibilities under ASPA, as well as one or more persons who are independent of the establishment (usually referred to as Lay People). Inspectors may also attend meetings of the AWERB from time to time as part of their responsibilities for monitoring compliance with the legislation. The Chair and Members of the UK ASC are appointed by the Secretary of State according to their skills, expertise and experience. They do not represent any organization or interest group. The ASC includes lay members with an interest in ethical issues related to the use of animals in scientific research. The ASC has a diverse range of expertise to meet its obligations under ASPA and can invite additional expertise where necessary. Comparison Composition of project evaluation bodies (in terms of expertise and relationship of members to a given institution) varies with the nature of the body (institutional versus public or government). Composition is more strictly defined for institutional bodies than for public bodies and varies among member states. In theory, membership must represent different areas of expertise as defined in Article 38 of Directive 2010/63/EU, regardless of the body’s nature. In practice, the expertise relevant to the research program of a given institution should be considered during the evaluation. If that expertise is not represented in the evaluation body, it can be sought on an ad hoc basis. Some evaluation bodies, LAB ANIMAL
especially public ones, might struggle to convene the required committee members, particularly if resources are scarce. This concern also raises the question of whether members of public bodies should be compensated for their service. In Germany, committee service is voluntary, but in the Netherlands, members receive financial compensation commensurate with the workload and the level of responsibility. RESPONSIBILITY FOR PROJECT AUTHORIZATION Once a project involving the use of animals has been evaluated, it must be authorized before it can be initiated. The project authorization process is very closely related to the evaluation process, as evaluation results must be communicated to the body responsible for project authorization, which is generally the public Competent Authority. France The Ministry of Higher Education and Research is responsible for project authorization in France. The process for project authorization is defined by the Decree4. The scientist responsible for the project must submit a description of the research project, including experimental procedures, to the Ministry. The Ministry then requests the institutional Ethics Committee to carry out the project evaluation and authorizes the project if the Ethics Committee’s evaluation has a positive outcome. Any amendments are evaluated and authorized following the same process. Authorization must be granted within 40 working days, but it is unclear whether this time period begins when the project description is received by the Ministry (as indicated in Directive 2010/63/EU) or when the project description has been registered and reviewed by Ministry services (as currently practiced by the Ministry). Germany In Germany, local authorities are responsible for authorizing animal experiments; these can be government bodies, veterinary authorities or state ministries. The person responsible for the authorization process is a veterinary official, who is not required to possess expertise in animal experimentation. After a project application has been authorized internally by an institution, the application is forwarded to the relevant local authority, which consults its own governmental Ethics Committee and makes a decision on the application (clearance or rejection). This decision may be guided by a recommendation for the assessment of suffering in genetically modified mouse lines16 drafted by the German Federal Institute for Risk Assessment. Spain Project authorization in Spain is the responsibility of the public competent authorities of the autonomous Volume 44, No. 1 | JANUARY 2015 29
Resource
npg
© 2015 Nature America, Inc. All rights reserved.
regions. There are no specific requirements in RD 53/2013 for the authorization process except for the time period of 40 working days or 55 working days (extended timeline) for authorization as defined in Directive 2010/63/EU. There is some concern regarding the ability of some competent authorities to respond within the established time period. Based on the Spanish legal system, tacit approval is considered to be given if no response has been received within the established time period. The Netherlands In the Netherlands, under the proposed regulation, project authorization will be granted by the transformed CCD, an independent public body that will also publish anonymous non-technical project summaries. This body will also control the recognition and compliance of AUCs and will have the discretional authority not to follow their advice. The CCD will issue common formats and other prescriptions for the ethical review process and will charge for its services. In addition, the CCD will operate under Dutch public law and will make rulings on freedom of information and appeal by parties with an interest, including third parties. These responsibilities exceed both current domestic legislation and the requirements of Directive 2010/63/EU. The UK In the UK, project authorization responsibility belongs to the Secretary of State. A Right of Appeal is available to applicants. Comparison In most cases, project authorization is the responsibility of government authorities, at either the regional or the national level, even when responsibility for project evaluation belongs to other bodies. This means that institutional evaluation bodies must ensure that their evaluation processes are adequate to minimize the risk of project authorization being denied for technical reasons. Denial of authorization would be problematic for researchers, as it would delay project initiation. It is the responsibility of the Competent Authority to designate well-constituted and efficient evaluation bodies and to inspect their performance of the delegated tasks. USE OF A PROJECT APPLICATION TEMPLATE Although Directive 2010/63/EU does not propose a common format for project applications, Article 38 lists the elements that shall be assessed during the evaluation process, and Article 37 and Annex VI list the elements that must be included in the application for authorization. The implementation of common templates for project applications is at the discretion of the member states. 30 Volume 44, No. 1 | JANUARY 2015
A national template has been developed in France by the Ministry of Research, with items as defined per Directive 2010/63/EU. This template is administrative in nature and not necessarily intended to facilitate appropriate ethical evaluation; therefore, many discussions may occur between the Ethics Committee and the person responsible for the project. Germany and the Netherlands each has a national template for project applications that includes the items listed in Article 38 of Directive 2010/63/EU. In Spain, there is no standardized national template for collecting the requested information, although development of a common template is a topic of frequent discussions within the Spanish laboratory animal science community. The project information presented to the Authorized Body transposes the items listed in Annex VI of Directive 2010/63/EU. The UK Home Office provides a template for project license applications that follows the criteria listed in Article 38 of Directive 2010/63/EU and that also includes the template for the non-technical summary. The template provides sections and notes on the type of content to be included. The value of using a standardized national template and the contents of such a template are matters for discussion. It may be difficult to merge in a single document all questions that may be relevant across very diverse areas of research, and templates tailored to the type of research and species used at each establishment might be more functional. On the other hand, a standardized template may facilitate project evaluation, especially when this is done by external or government bodies. Because projects can be authorized for up to 5 years, the level of detail requested in the templates is an important point for consideration. The information provided must be sufficient to enable evaluation bodies to carry out an appropriate evaluation, but it may be very difficult to include all details of a complex project for such a long period of time. Variation of experimental procedures is quite common, and so specific details (e.g., anesthetic doses for all species and procedures) may not accurately represent actual experimental procedures. To allow flexibility and to cover changes that were unanticipated at the beginning of the 5-year project, amendments can be prepared, evaluated and authorized; this is common practice in the UK. However, some researchers already consider the bureaucratic burden to be great, and it would be further increased by the use of project application amendments. The use of more generic terms in the template might be a good compromise, but opinions on how these generic terms are defined may differ. CONCLUSIONS Evaluation of animal research projects is not a new practice in Europe but is now mandatory under Directive 2010/63/EU, which has had to be transposed www.labanimal.com
Resource
npg
© 2015 Nature America, Inc. All rights reserved.
into member states’ laws. Previous approaches to project evaluation in Europe included the participation of national committees, regional committees, institutional committees, external (contract) committees, animal welfare officers and veterinary inspectors. After transposition of Directive 2010/63/EU, there is still variation in approaches to project evaluation in EU, which may be partially explained by the differences in resources and experience across member states. Despite this variation, all project evaluation processes should implement the key elements and principles of Directive 2010/63/EU in an impartial manner to ensure a similar high level of ethical evaluation (including harm–benefit analysis) and animal welfare across Europe. No single practical approach will fit all member states. Strategies that are feasible and effective in member states with long experience in ethical evaluation and strong and dedicated public bodies may not be applicable to other member states lacking those resources and expertise. A performance-based approach is the key to developing an appropriate approach to project evaluation that incorporates the elements of Directive 2010/63/EU. Article 59, allowing for delegation of responsibility for project evaluation, seems to be a sensible feature of Directive 2010/63/EU, as it allows member states to develop systems that are appropriate given the resources available and the expertise of public Competent Authorities and research establishments. Approaches may vary, but the outcome should be the same: animals should be used only when justified and necessary; the number of animals used should be the fewest needed to meet the scientific objectives proposed; and projects should follow animal care and use standards that minimize animal pain, suffering and distress. COMPETING FINANCIAL INTERESTS The authors declare no competing financial interests. Received 17 February 2014; accepted 7 July 2014 Published online at http://www.labanimal.com/ 1. EEC. Directive 86/609/EEC of 24 November 1986 on the approximation of laws, regulations and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes. EEC Official Journal L358, 1–28 (1986). 2. Smith, J.A. et al. Principles and practice in ethical review of animal experiments across Europe: summary of the report of a FELASA working group on ethical evaluation of animal experiments. Lab. Anim. 41, 143–160 (2007).
LAB ANIMAL
3. European Union. Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes. Official Journal of the European Union L276, 33–79 (2010). 4. République Française. Décret no 2013-118 du 1er février 2013 relatif à la protection des animaux utilisés à des fins scientifiques. JORF 0032, 2199 (2013). 5. République Française. Arrêté du 1er février 2013 relatif à l’évaluation éthique et à l’autorisation des projets impliquant l’utilisation d’animaux dans des procédures expérimentales. JORF 0032, 2228 (2013). 6. Commission Nationale de Réflexion Ethique sur l’Expérimentation Animale (2008). 7. GIRCOR. Guide for the Ethical Evaluation of Experiments Using Laboratory Animals (2009). 8. Tierschutzgesetz in der Fassung der Bekanntmachung vom 18. Mai 2006 (BGBl. I S. 1206, 1313), das durch Artikel 1 des Gesetzes vom 4. Juli 2013 (BGBl. I S. 2182) geändert worden ist. 9. Verordnung zur Umsetzung der Richtlinie 2010/63/EU des Europäischen Parlaments und des Rates vom 22. September 2010 zum Schutz der für wissenschaftliche Zwecke verwendeten Tiere. Vom 1. August 2013. 10. Ministerio de la Presidencia, España. Real Decreto 53/2013 de 1 de Febrero, por el que se establecen las normas básicas aplicables para la protección de los animales utilizados en experimentación y otros fines científicos, incluyendo la docencia. BOE 34, 11370–11421 (2013). 11. Wet op de dierproeven (Animal Experiments Act). and Dierproevenbesluit (Animal Testing Decision) 12. NVWA. Zo doende 2011. Annual report of the Netherlands Food and Consumer Product Safety Authority (NVWA) about animal experimentation and laboratory animals in 2011. (Neder landse Voedsel- en Warenautoriteit, Utrecht, The Netherlands, 2012) 13. Animals (Scientific Procedures) Act 1986 Chapter 14, http://www.legislation.gov.uk/ukpga/1986/14. 14. The Animals (Scientific Procedures) Act 1986 Amendment Regulations 2012 (Statutory Instruments 2012 No. 3039: Animals). 15. Jefatura del Estado, España. Ley 30/1992, de 26 de Noviembre, de Régimen Jurídico de las Administraciones Públicas y del Procedimiento Administrativo Común. BOE 285, 40300–40319 (1992). 16. Deutsche Übersetzung mit Erläuterungen und Empfehlungen des Workshops Dokumentation und Veröffentlichung der Belastungseinstufung genetisch veränderter Versuchstiere am Bundesinstitut für Risikobewertung, Berlin 20–21 Juni 2013.
Volume 44, No. 1 | JANUARY 2015 31
Approaches to animal research project evaluation in Europe after implementation of Directive 2010/63/EU Javier Guillén, DVM1, Sally Robinson, PhD2, Thierry Decelle, DVM, DipVetLAS3, Cornelia Exner, PhD4 & Martje Fentener van Vlissingen, DVM, PhD, DipECLAM5
© 2015 Nature America, Inc. All rights reserved.
Directive 2010/63/EU requires the evaluation and authorization of all research projects and training activities involving the use of animals and defines some components and expertise necessary for the evaluation process. Adoption of Directive 2010/63/EU provided an opportunity to harmonize project evaluation processes across Europe, but thus far, member states have used a variety of approaches in the transposition and implementation of Directive 2010/63/EU. The authors discuss and compare the project evaluation systems being implemented in five European Union member states (France, Germany, Spain, the Netherlands and the UK).
npg
Prior to 2010, research using animals in European Union (EU) member states was guided by Directive 86/609/EEC1, which did not require evaluation of animal research proposals. Several countries did have national regulations that included this requirement, however, and ethical evaluation was done at some establishments in other countries for reasons such as institutional commitment, good practice and funding or accreditation requirements. The evaluation systems in place differed with respect to the composition of evaluation committees; the type of information provided; the factors considered during the evaluation; the training of participants; and the participation of institutional, external and government bodies. A 2007 report by the Federation of European Laboratory Animal Science Associations (FELASA) illustrated the heterogeneity of project evaluation practices in Europe2 but also identified certain key elements included in all ethical evaluation processes and proposed a set of recommendations for appropriate ethical review2. In 2010, Directive 2010/63/EU3 came into force. It contains 59 introductory Recitals, 66 effective Articles and 8 Annexes (Table 1). Directive 2010/63/EU requires the evaluation and authorization of all research projects and training activities involving the use of animals. Its requirements for project evaluation include
the criteria that a project should meet; the components of the project evaluation, including a harm–benefit analysis; the expertise to be considered for the evaluation process; and the need for transparency. Directive 2010/63/EU also states that the evaluation shall be done in an impartial manner and may integrate the opinion of independent parties. Several bodies or persons have oversight functions under Directive 2010/63/EU that may or may not be directly involved in project evaluation (Table 2). First, the Competent Authority is the body designated by a member state to carry out the obligations arising from Directive 2010/63/EU. This is normally a national or regional government body. Second, the institutional Animal Welfare Body (AWB) has an advisory role in matters such as animal welfare, implementation of the principles of the 3Rs, follow-up of projects and rehoming schemes. Third, the person responsible for overseeing the welfare and care of the animals in the establishment or Animal Welfare Officer (AWO) must be a member of the AWB. Fourth, the national committee for the protection of animals used for scientific purposes has an advisory role to the Competent Authority and the AWBs. Finally, bodies other than public authorities can be designated by the Competent Authority for the implementation of specific tasks laid down in Directive 2010/63/EU.
1AAALAC International, Pamplona, Spain. 2AstraZeneca, Cheshire, UK. 3Sanofi Pasteur, Lyon, France. 4University of Marburg, Marburg, Germany. 5Erasmus MC, Rotterdam, the Netherlands. Correspondence should be addressed to J.G. ([email protected]).
LAB ANIMAL
Volume 44, No. 1 | JANUARY 2015 23
Resource
TABLE 1 | Contents of selected Articles and Annexes in Directive 2010/63/EU
npg
© 2015 Nature America, Inc. All rights reserved.
Article
Content
3
Definitions
6, Annex IV
Approved methods of humane killing (per species), exemptions for emergencies, research requirements for equally (or more) humane methods
19
Freeing and rehoming of animals to external parties at end of procedure
24
AWO tasks
26
AWB composition
27
AWB tasks
36–45, Annex VI
Procedures for granting, renewing, amending and withdrawing project licenses, including requirements for non-technical summaries and retrospective assessment
38
Procedures and criteria for ethical review of project license applications
49
National committees
55
Safeguard clauses for allowing exceptions (species, severity) where consent of Ethics Committees must be sought
59
Competent Authority and delegation of functions to other bodies
The adoption of Directive 2010/63/EU provided an opportunity to harmonize project evaluation practices across Europe. But member states have used various approaches to the transposition and implementation of Directive 2010/63/EU, resulting in variation in project evaluation processes among the member states. This variation may relate to the nature, roles, composition and expertise of the bodies responsible for project evaluation, which may affect the speed, flexibility and output of the evaluation process. In this article, we present, discuss and compare the approaches to project evaluation that have been implemented in
five EU member states: France, Germany, Spain, the Netherlands and the UK. RESPONSIBILITY FOR PROJECT EVALUATION Directive 2010/63/EU gives the responsibility for carrying out project evaluation to the Competent Authority, but it also allows member states to designate bodies other than public authorities for the implementation of specific tasks, including project evaluation. As a result, some member states allow the designation of AWBs and other institutional or external committees for project evaluation (Table 3).
TABLE 2 | Oversight functions defined in Directive 2010/63/EU and their roles in five EU member states Name; role Body or person
Level
France
Germany
Spain
The Netherlands
The UK
Competent Authority
National or regional
Regional inspectors; project authorization
Regional committees; project evaluation
Regional Competent Authorities; implementation and decisions
CCD; project authorization
Home Office Inspectorate; project evaluation
AWB
Institutional
Advisory
Advisory
Advisory
Advisory
Advisory
AWO
Institutional
General oversight
More authority than AWB
General oversight
General oversight
General oversight
National committee for the protection of animals used for scientific purposes
National
Advisory
Advisory
Advisory
Advisory
ASC; advisory
Other designated bodies
Institutional or external
Ethics Committee designated for project evaluation
Institutional AWBs or external authorized bodies designated for project evaluation
Institutional or external review bodies designated for project evaluation
24 Volume 44, No. 1 | JANUARY 2015
www.labanimal.com
Resource
TABLE 3 | Project evaluation and authorization processes in five EU member states France
Germany
Spain
Institutional Ethics Committees (independent from AWBs)
Competent Authority assisted by regional Ethics Committees
Institutional or external Authorized Bodies
Institutional or external ethics committees
Home Office Inspectorate and institutional AWERBs
Role of AWB in project evaluation
No
Yes
Yes
Yes
Yes
Composition of evaluation body
Scientist, technician, animal caretaker or person in charge of killing of animals, veterinarian and member not from the establishment
Per Article 38
Per Article 38 when the AWB is responsible: AWO, researcher(s) not involved in the project, and person with knowledge and expertise in animal welfare not related to the experiment and the user
Per Article 38 plus an expert on ethical review; majority of members should not be employed by the institution
For AWERB, at least one Named Animal Care and Welfare Officer, at least one Named Veterinary Surgeon and scientific member
Body responsible for project authorization
Ministry of Higher Education and Research
Regional Competent Authorities
Regional Competent Authorities
CCD
Secretary of State
Existence of national project application template
Yes
Yes
No
Yes
Yes
Body responsible for project
© 2015 Nature America, Inc. All rights reserved.
evaluation
npg
France In France, Directive 2010/63/EU was transposed as a Decree4 and its related Arrêté5 (an order with more detailed enforcement instructions coming from the Decree) as of 1 February 2013. Under these regulations, an establishment must set up two different oversight bodies that are independent but have complementary missions: the institutional Ethics Committee and the AWB. The Ethics Committee is responsible for project evaluation, whereas the AWB has advisory functions as described in Article 27 of Directive 2010/63/EU. One Ethics Committee can cover several establishments, but each establishment should have a specifically designated Ethics Committee, which must be registered with the Ministry of Research. Rules governing the function of Ethics Committees are defined in the regulations and in the National Charter on the Ethics of Animal Experimentation6, which was issued in 2009 by the National Ethical Committee on Animal Experimentation and needs to be updated in accordance with the new requirements of Directive 2010/63/EU. The charter includes some guidance on project evaluation with flexibility for adjustments in accordance with research programs and with the size and complexity of the establishment but does not define a specific deliberation or decision process, except in the case of a conflict of interest. The framework for project evaluation in LAB ANIMAL
The Netherlands
The UK
France is mainly derived from the Guide for the Ethical Evaluation of Experiments Using Laboratory Animals7 issued by Gircor, an association of professionals from French public and private research institutions, in 2009, before regulations required a formal review process. The Guide for the Ethical Evaluation of Experiments Using Laboratory Animals is widely used as a reference by the Ministry of Research, by Ethics Committees and by establishments in France and needs to be updated to reflect the requirements of the new regulations. Since 2008, training sessions have been carried out to ensure the competency of project evaluators and the coordination of evaluations. Annual audits are carried out to ensure compliance and include review by a regional representative of the Ministry of Research and inspection by the Ethics Committee. Veterinary inspectors also review animal use and the implementation of the principles of the 3Rs (reduction, replacement and refinement). Germany In Germany, Directive 2010/63/EU is transposed into the revised Animal Welfare Act, which took effect on 4 July 2013 (ref. 8). An ordinance9 that regulates the implementation in detail was also issued. These new regulations have not resulted in substantial changes to the parties responsible for project evaluation or to the evaluation process. Regional Ethics Committees Volume 44, No. 1 | JANUARY 2015 25
Resource
npg
© 2015 Nature America, Inc. All rights reserved.
composed of expert volunteers are responsible for project evaluation. The plausibility and ethics of project applications are reviewed and evaluated by an appropriate party (government body, veterinary authority or state ministry) as determined by the regional Ethics Committee. Pain, suffering and lasting harm caused to the animals are taken into account, and harm–benefit analyses are done. Implementation of Directive 2010/63/EU has made the process more complex and time-consuming, however. The definition of animal experiments has been expanded: for example, the breeding of altered transgenic lines is now permanently subject to authorization requirements, and experiments for the purpose of education, training and advanced training are now subject to more extensive review. Spain In Spain, transposition of Directive 2010/63/EU ended with the publication of Royal Decree 53/2013 (RD 53/2013; ref. 10). Under RD 53/2013, entities named Authorized Bodies carry out specific functions designated by the regional public competent authorities. Authorized Bodies are explicitly assigned to carry out project evaluation. Authorized Bodies are registered with the central government and can be used by registered establishments. Animal Welfare Bodies in user establishments may become Authorized Bodies. The criteria for the evaluation process to be used by Authorized Bodies are copied from Article 38 of Directive 2010/63/EU and include the concepts of transparency and impartiality. In line with Directive 2010/63/EU, RD 53/2013 emphasizes that Authorized Bodies must have the technical expertise and infrastructure necessary for the task and must operate without any conflicts of interest. The national committee for the protection of animals used for scientific purposes has no project evaluation functions but has the role of advisement and coordination. The Netherlands The Dutch government has chosen to adapt the current law on the protection of animals used for research (Animal Experiments Act11) to comply with Directive 2010/63/EU. The process of transposition is ongoing; it was overseen by the Ministry of Public Health through 2012 and by the Ministry of Economic Affairs (also responsible for agricultural policy and animal welfare) since January 2013. In 2013, the changes in the regulations were prepared for parliamentary approval. The House of Representatives approved the changes in December 2013, with some amendments; the Senate still has to vote on the changes (but is not allowed to amend the regulations, only to approve them or to redirect them to the government). The present law already requires ethical evaluation of the use of animals for research or training. Approximately 20 Animal Use Committees (AUCs) are responsible for project evaluation; 26 Volume 44, No. 1 | JANUARY 2015
these are formally recognized and mandated by the Minister. Most AUCs are institutional, some serve more than one establishment, and a few are independent. The workload of the different AUCs varies substantially (in terms of both number and diversity of project applications, which total more than 4,000 annually12), and some AUCs operate subcommittees. The process of project evaluation and licensing will be substantially different if the currently proposed changes come into force. Project evaluation will be split over three different levels of review, and establishment of the AWB will intensify internal evaluation. Draft applications for project licenses will be previewed by the AWB in view of local provisions, expertise and facilities. The AWB will take over the detailed technical evaluation in view of best practices and application of the principles of the 3Rs. Once a project has been licensed, the AWB will have a key advisory role in its execution. Ethical evaluation will be done by a recognized review body and then reviewed by the Competent Authority (Central Committee on Animal Experiments, CCD). This threelevel review process will partially dissociate technical and ethical review, creating better opportunities for ethical discussion, and should make procedures more consistent nationally. The new processes may present some challenges in view of efficiency and the meeting of deadlines. Furthermore, both the administrative burden and the costs of review procedures for projects and establishments will rise substantially. The UK In the UK, the use of animals in experiments and testing is regulated under the Animals (Scientific Procedures) Act 1986 (ASPA)13. ASPA has recently been revised to transpose Directive 2010/63/EU. The revised legislation came into force on 1 January 2013 (ref. 14). Standard project license applications are evaluated by two oversight bodies. The first evaluation by the Animal Welfare and Ethical Review Body (AWERB) allows for local knowledge, expertise, 3Rs principles and best practice to be discussed and incorporated. The new AWERBs, in most respects, continue and develop the work of the local Ethical Review Processes that they replaced on 1 January 2013. The second, formal project evaluation (including the harm–benefit analysis) is done by the Competent Authority (the Home Office Inspectorate) and relies on professional judgment, continuous professional development, knowledge–sharing, scientific literature precedents and external views (e.g., from the Animals in Science Committee (ASC) or other expert assessors). The ASC is an independent, public body set up under ASPA and responsible for providing impartial, balanced and objective advice to the Home Office. Certain project license applications may be referred to the ASC, including those that involve the use of wild-caught nonhuman primates; those that involve www.labanimal.com
Resource
the use of cats, dogs, equidae or nonhuman primates in severe procedures; those that involve the use of endangered species; and those that invoke any of the safeguard clauses (reasons for the Competent Authority to accept exceptions) in Directive 2010/63/EU with respect to the purpose of nonhuman primate use, proposals for the use of a great ape or proposals to cause long-lasting pain, suffering or distress that cannot be ameliorated.
npg
© 2015 Nature America, Inc. All rights reserved.
Comparison Some member states assign the responsibility for project evaluation to the Competent Authority, whereas others delegate this responsibility to institutional or external bodies. Pragmatism may form the basis of this decision for many member states, particularly those lacking sufficient and trained human resources to carry out appropriate project evaluation. Government bodies responsible for the control of animals in research might not have the resources to support this or might lack the personnel and expertise and might therefore rely on other, more specialized bodies for project evaluation. In these cases, it is important to consider whether the impartiality required by Directive 2010/63/EU can be assured by institutional bodies. Impartiality in a small institution might be hard to guarantee, particularly if there are only a few researchers, if they all work in the same field and if the institution depends on the rapid development of projects. It might be easier for a larger institution to establish a committee with a composition broad enough to minimize conflicts of interest. External independent parties, including committees belonging to larger institutions, can be incorporated into the project evaluation process in order to guarantee impartiality. In member states that assign the responsibility for project evaluation to the Competent Authority, such as Germany and the UK, preliminary evaluation at the institutional level is common, whereas in those that delegate this responsibility to institutional or external bodies, such as France, Spain and the Netherlands, project authorization by the Competent Authority after evaluation is common, allowing the Competent Authority to inspect the work of the designated bodies. In both cases, collaboration between institutional bodies and the Competent Authority is beneficial. ROLE OF AWB IN PROJECT EVALUATION The AWB is an institutional entity that, under Directive 2010/63/EU, has an advisory role on matters related to animal welfare, including the establishment and review of processes to monitor and report on these matters; on implementation of the 3Rs; on the development and outcome of projects; and on rehoming schemes. Directive 2010/63/EU does not assign project evaluation responsibility to the AWB, but in member states that delegate this responsibility to institutional bodies, it seems reasonable for AWBs to form the basis for these bodies, LAB ANIMAL
expanding their composition to fulfill the requirements for expertise and to guarantee impartiality. In practice, the involvement of AWBs in project evaluation varies among member states. France In France, the AWB is not involved in project evaluation but functions in an advisory role as described in Article 27 of Directive 2010/63/EU, acting at an institutional level with knowledge of resources, policies and procedures and ensuring the implementation of good practices regarding animal welfare and use and the principles of the 3Rs. Germany In Germany, institutional AWBs are not involved in project evaluation but function in an advisory role. Each AWB is chaired by an AWO, who initially discusses project applications with the applicants. The meeting minutes of the AWB may be reviewed by the Competent Authority responsible for project authorization. Spain In Spain, AWBs can be named Ethics Committees for Animal Experimentation and can be designated as Authorized Bodies when they comply with all the criteria for project evaluation. This is interpreted in some cases to allow institutional AWBs (or Ethics Committees) to evaluate institutional projects. This might seem to be a pragmatic solution because many of Spain’s Competent Authorities lack the resources and expertise for project evaluation, but it presents a potential conflict of interest. In regard to the issue of conflict of interest, RD 53/2013 refers to a Law from 1992 (Ley 30/1992; ref. 15) ruling on the functioning of public bodies, which strictly defines what constitutes such a conflict. On the basis of this law, some Competent Authorities do not allow institutional Authorized Bodies to evaluate projects at their own institutions, whereas others do as long as the members of the Authorized Body are not themselves involved in the proposed project. When impartiality of an institutional Authorized Body cannot be guaranteed, project evaluation may need to be done by an external Authorized Body. Use of an external Authorized Body could be problematic when it comes to retrospective assessment, which includes the evaluation of whether the objectives of the project were achieved; the harm inflicted to animals (number, species and severity); and the elements that may contribute to the further implementation of the principles of 3Rs and is required for all projects using nonhuman primates and all projects including procedures categorized as severe. The Netherlands Under the currently proposed regulations, AWBs in the Netherlands will have a broad role in project Volume 44, No. 1 | JANUARY 2015 27
Resource
npg
© 2015 Nature America, Inc. All rights reserved.
evaluation. Draft applications for project licenses will be previewed by the AWBs in view of local provisions, expertise and facilities available. Then, when the project license comes into use, the AWB will carry out detailed technical evaluation of single study protocols, applying approved strategies for minimizing severity and the number of animals used. The AWB will also advise on project development and carry out retrospective reporting. The UK In terms of project evaluation, the UK AWERB has an advisory role, providing guidance to each establishment’s license holder on whether to support project proposals, providing local expertise during the development of new license applications and identifying specific issues that need to be addressed. This role also enables the AWERB to fulfill the guidance of Article 27(1d) of Directive 2010/63/EU to “follow the development and outcome of projects”. The AWERB provides essential advice on animal welfare and scientific aspects of applications, including local and institutional standards. Comparison Comparing the different responsibilities of the AWB across countries shows that project evaluation is no longer the only task assigned to institutional review bodies. Other oversight and advisory functions are now assigned to AWBs, with the intention of creating a culture of care and promoting the application of the principles of the 3Rs. Specific functions may include advising on matters related to the welfare, acquisition, accommodation, care and use of animals; advising on the application of the principles of the 3Rs and relevant technical and scientific developments; establishing and reviewing internal operational processes such as monitoring, reporting and follow-up on matters involving the welfare of animals housed or used in the establishment; following the development and outcome of projects, including the effect on the animals used, and identifying elements that may enhance application of the principles of the 3Rs; and advising on rehoming schemes, including the appropriate socialization of the animals to be rehomed. It may be a matter for individual establishments to determine whether to add review functions to the tasks of the AWB when project evaluation is assigned to other bodies (e.g., Ethics Committees or government authorities) in order to ensure that project applications are well-prepared and conform to institutional policies. This has been done in many establishments across Europe even though there was no legal mandate to do so. AWOs, veterinarians or fully constituted institutional review bodies have been operating to ensure consistency and good practice in research proposals submitted to Competent Authorities. In cases 28 Volume 44, No. 1 | JANUARY 2015
where project evaluation responsibility is retained by the Competent Authority, the AWB can ensure that other activities are carried out. However, the emphasis of Directive 2010/63/EU on the advisory nature of the AWB’s functions may jeopardize its authority, depending on each institution’s level of commitment. COMPOSITION OF PROJECT EVALUATION BODIES Article 26 of Directive 2010/63/EU indicates that the AWB shall include at least the AWO and, in the case of user establishments, a scientific member. It shall also receive input from the designated veterinarian or the expert referred to in Article 25. But Directive 2010/63/EU does not indicate specific requirements for the composition of the body (Competent Authority) responsible for project evaluation. It indicates only that expertise in the following areas shall be considered: (i) the areas of scientific use for which animals will be used, including replacement, reduction and refinement in the respective areas; (ii) experimental design, including statistics, where appropriate; (iii) veterinary practice in laboratory animal science or wildlife veterinary practice, where appropriate; and (iv) animal husbandry and care. It indicates that the project evaluation process shall be transparent while safeguarding intellectual property and confidential information, shall be carried out in an impartial manner and may integrate the opinion of independent parties. These requirements allow variation in the composition of the project evaluation body while also necessitating that AWBs that have been assigned the responsibility for project evaluation function expand their composition to ensure transparency and impartiality. France French Ethics Committees responsible for project evaluation must include members representing five different functions: scientist, technician, animal caretaker or person in charge of killing of animals, veterinarian and lay member. Impartiality is guaranteed by national charter and law. Ethics Committee members sign a formal commitment to withdraw from the evaluation if any conflicts of interest are anticipated. Germany The members of the German Ethics Committees in charge of project evaluation come from research, industry and animal welfare organizations. The majority of them must have a basic academic education. Their work is done on a voluntary basis, and they report to the local authority responsible for project authorization. The AWOs and the local authorities are independent as required by the German Animal Welfare Act. Spain In Spain, where the new legislation allows AWBs to be authorized to carry out project evaluation, an authorized www.labanimal.com
Resource
AWB must comprise the AWO; researcher(s) not involved in the project; and a person with knowledge and expertise in animal welfare not related to the experiment and the establishment. The Netherlands The altered legislation in the Netherlands would maintain AUCs but adapt their composition to comply with Article 38 of Directive 2010/63/EU (fields of expertise) and maintain the provisions for freedom of conflict of interests.
npg
© 2015 Nature America, Inc. All rights reserved.
The UK The revised UK legislation specifies that the AWERB must have, as full members, at least one of the establishment’s Named Animal Care and Welfare Officers and at least one Named Veterinary Surgeon. For an establishment, the AWERB must also include a scientific member and should ensure that other named persons, including the Named Information Officer and the Named Training and Competency Officer, are actively engaged with the AWERB, as its tasks are far broader than local project evaluation. Establishment license holders should arrange for their AWERBs to actively seek a wider membership taking into account, in a transparent manner, the views of people who do not have responsibilities under ASPA, as well as one or more persons who are independent of the establishment (usually referred to as Lay People). Inspectors may also attend meetings of the AWERB from time to time as part of their responsibilities for monitoring compliance with the legislation. The Chair and Members of the UK ASC are appointed by the Secretary of State according to their skills, expertise and experience. They do not represent any organization or interest group. The ASC includes lay members with an interest in ethical issues related to the use of animals in scientific research. The ASC has a diverse range of expertise to meet its obligations under ASPA and can invite additional expertise where necessary. Comparison Composition of project evaluation bodies (in terms of expertise and relationship of members to a given institution) varies with the nature of the body (institutional versus public or government). Composition is more strictly defined for institutional bodies than for public bodies and varies among member states. In theory, membership must represent different areas of expertise as defined in Article 38 of Directive 2010/63/EU, regardless of the body’s nature. In practice, the expertise relevant to the research program of a given institution should be considered during the evaluation. If that expertise is not represented in the evaluation body, it can be sought on an ad hoc basis. Some evaluation bodies, LAB ANIMAL
especially public ones, might struggle to convene the required committee members, particularly if resources are scarce. This concern also raises the question of whether members of public bodies should be compensated for their service. In Germany, committee service is voluntary, but in the Netherlands, members receive financial compensation commensurate with the workload and the level of responsibility. RESPONSIBILITY FOR PROJECT AUTHORIZATION Once a project involving the use of animals has been evaluated, it must be authorized before it can be initiated. The project authorization process is very closely related to the evaluation process, as evaluation results must be communicated to the body responsible for project authorization, which is generally the public Competent Authority. France The Ministry of Higher Education and Research is responsible for project authorization in France. The process for project authorization is defined by the Decree4. The scientist responsible for the project must submit a description of the research project, including experimental procedures, to the Ministry. The Ministry then requests the institutional Ethics Committee to carry out the project evaluation and authorizes the project if the Ethics Committee’s evaluation has a positive outcome. Any amendments are evaluated and authorized following the same process. Authorization must be granted within 40 working days, but it is unclear whether this time period begins when the project description is received by the Ministry (as indicated in Directive 2010/63/EU) or when the project description has been registered and reviewed by Ministry services (as currently practiced by the Ministry). Germany In Germany, local authorities are responsible for authorizing animal experiments; these can be government bodies, veterinary authorities or state ministries. The person responsible for the authorization process is a veterinary official, who is not required to possess expertise in animal experimentation. After a project application has been authorized internally by an institution, the application is forwarded to the relevant local authority, which consults its own governmental Ethics Committee and makes a decision on the application (clearance or rejection). This decision may be guided by a recommendation for the assessment of suffering in genetically modified mouse lines16 drafted by the German Federal Institute for Risk Assessment. Spain Project authorization in Spain is the responsibility of the public competent authorities of the autonomous Volume 44, No. 1 | JANUARY 2015 29
Resource
npg
© 2015 Nature America, Inc. All rights reserved.
regions. There are no specific requirements in RD 53/2013 for the authorization process except for the time period of 40 working days or 55 working days (extended timeline) for authorization as defined in Directive 2010/63/EU. There is some concern regarding the ability of some competent authorities to respond within the established time period. Based on the Spanish legal system, tacit approval is considered to be given if no response has been received within the established time period. The Netherlands In the Netherlands, under the proposed regulation, project authorization will be granted by the transformed CCD, an independent public body that will also publish anonymous non-technical project summaries. This body will also control the recognition and compliance of AUCs and will have the discretional authority not to follow their advice. The CCD will issue common formats and other prescriptions for the ethical review process and will charge for its services. In addition, the CCD will operate under Dutch public law and will make rulings on freedom of information and appeal by parties with an interest, including third parties. These responsibilities exceed both current domestic legislation and the requirements of Directive 2010/63/EU. The UK In the UK, project authorization responsibility belongs to the Secretary of State. A Right of Appeal is available to applicants. Comparison In most cases, project authorization is the responsibility of government authorities, at either the regional or the national level, even when responsibility for project evaluation belongs to other bodies. This means that institutional evaluation bodies must ensure that their evaluation processes are adequate to minimize the risk of project authorization being denied for technical reasons. Denial of authorization would be problematic for researchers, as it would delay project initiation. It is the responsibility of the Competent Authority to designate well-constituted and efficient evaluation bodies and to inspect their performance of the delegated tasks. USE OF A PROJECT APPLICATION TEMPLATE Although Directive 2010/63/EU does not propose a common format for project applications, Article 38 lists the elements that shall be assessed during the evaluation process, and Article 37 and Annex VI list the elements that must be included in the application for authorization. The implementation of common templates for project applications is at the discretion of the member states. 30 Volume 44, No. 1 | JANUARY 2015
A national template has been developed in France by the Ministry of Research, with items as defined per Directive 2010/63/EU. This template is administrative in nature and not necessarily intended to facilitate appropriate ethical evaluation; therefore, many discussions may occur between the Ethics Committee and the person responsible for the project. Germany and the Netherlands each has a national template for project applications that includes the items listed in Article 38 of Directive 2010/63/EU. In Spain, there is no standardized national template for collecting the requested information, although development of a common template is a topic of frequent discussions within the Spanish laboratory animal science community. The project information presented to the Authorized Body transposes the items listed in Annex VI of Directive 2010/63/EU. The UK Home Office provides a template for project license applications that follows the criteria listed in Article 38 of Directive 2010/63/EU and that also includes the template for the non-technical summary. The template provides sections and notes on the type of content to be included. The value of using a standardized national template and the contents of such a template are matters for discussion. It may be difficult to merge in a single document all questions that may be relevant across very diverse areas of research, and templates tailored to the type of research and species used at each establishment might be more functional. On the other hand, a standardized template may facilitate project evaluation, especially when this is done by external or government bodies. Because projects can be authorized for up to 5 years, the level of detail requested in the templates is an important point for consideration. The information provided must be sufficient to enable evaluation bodies to carry out an appropriate evaluation, but it may be very difficult to include all details of a complex project for such a long period of time. Variation of experimental procedures is quite common, and so specific details (e.g., anesthetic doses for all species and procedures) may not accurately represent actual experimental procedures. To allow flexibility and to cover changes that were unanticipated at the beginning of the 5-year project, amendments can be prepared, evaluated and authorized; this is common practice in the UK. However, some researchers already consider the bureaucratic burden to be great, and it would be further increased by the use of project application amendments. The use of more generic terms in the template might be a good compromise, but opinions on how these generic terms are defined may differ. CONCLUSIONS Evaluation of animal research projects is not a new practice in Europe but is now mandatory under Directive 2010/63/EU, which has had to be transposed www.labanimal.com
Resource
npg
© 2015 Nature America, Inc. All rights reserved.
into member states’ laws. Previous approaches to project evaluation in Europe included the participation of national committees, regional committees, institutional committees, external (contract) committees, animal welfare officers and veterinary inspectors. After transposition of Directive 2010/63/EU, there is still variation in approaches to project evaluation in EU, which may be partially explained by the differences in resources and experience across member states. Despite this variation, all project evaluation processes should implement the key elements and principles of Directive 2010/63/EU in an impartial manner to ensure a similar high level of ethical evaluation (including harm–benefit analysis) and animal welfare across Europe. No single practical approach will fit all member states. Strategies that are feasible and effective in member states with long experience in ethical evaluation and strong and dedicated public bodies may not be applicable to other member states lacking those resources and expertise. A performance-based approach is the key to developing an appropriate approach to project evaluation that incorporates the elements of Directive 2010/63/EU. Article 59, allowing for delegation of responsibility for project evaluation, seems to be a sensible feature of Directive 2010/63/EU, as it allows member states to develop systems that are appropriate given the resources available and the expertise of public Competent Authorities and research establishments. Approaches may vary, but the outcome should be the same: animals should be used only when justified and necessary; the number of animals used should be the fewest needed to meet the scientific objectives proposed; and projects should follow animal care and use standards that minimize animal pain, suffering and distress. COMPETING FINANCIAL INTERESTS The authors declare no competing financial interests. Received 17 February 2014; accepted 7 July 2014 Published online at http://www.labanimal.com/ 1. EEC. Directive 86/609/EEC of 24 November 1986 on the approximation of laws, regulations and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes. EEC Official Journal L358, 1–28 (1986). 2. Smith, J.A. et al. Principles and practice in ethical review of animal experiments across Europe: summary of the report of a FELASA working group on ethical evaluation of animal experiments. Lab. Anim. 41, 143–160 (2007).
LAB ANIMAL
3. European Union. Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes. Official Journal of the European Union L276, 33–79 (2010). 4. République Française. Décret no 2013-118 du 1er février 2013 relatif à la protection des animaux utilisés à des fins scientifiques. JORF 0032, 2199 (2013). 5. République Française. Arrêté du 1er février 2013 relatif à l’évaluation éthique et à l’autorisation des projets impliquant l’utilisation d’animaux dans des procédures expérimentales. JORF 0032, 2228 (2013). 6. Commission Nationale de Réflexion Ethique sur l’Expérimentation Animale (2008). 7. GIRCOR. Guide for the Ethical Evaluation of Experiments Using Laboratory Animals (2009). 8. Tierschutzgesetz in der Fassung der Bekanntmachung vom 18. Mai 2006 (BGBl. I S. 1206, 1313), das durch Artikel 1 des Gesetzes vom 4. Juli 2013 (BGBl. I S. 2182) geändert worden ist. 9. Verordnung zur Umsetzung der Richtlinie 2010/63/EU des Europäischen Parlaments und des Rates vom 22. September 2010 zum Schutz der für wissenschaftliche Zwecke verwendeten Tiere. Vom 1. August 2013. 10. Ministerio de la Presidencia, España. Real Decreto 53/2013 de 1 de Febrero, por el que se establecen las normas básicas aplicables para la protección de los animales utilizados en experimentación y otros fines científicos, incluyendo la docencia. BOE 34, 11370–11421 (2013). 11. Wet op de dierproeven (Animal Experiments Act). and Dierproevenbesluit (Animal Testing Decision) 12. NVWA. Zo doende 2011. Annual report of the Netherlands Food and Consumer Product Safety Authority (NVWA) about animal experimentation and laboratory animals in 2011. (Neder landse Voedsel- en Warenautoriteit, Utrecht, The Netherlands, 2012) 13. Animals (Scientific Procedures) Act 1986 Chapter 14, http://www.legislation.gov.uk/ukpga/1986/14. 14. The Animals (Scientific Procedures) Act 1986 Amendment Regulations 2012 (Statutory Instruments 2012 No. 3039: Animals). 15. Jefatura del Estado, España. Ley 30/1992, de 26 de Noviembre, de Régimen Jurídico de las Administraciones Públicas y del Procedimiento Administrativo Común. BOE 285, 40300–40319 (1992). 16. Deutsche Übersetzung mit Erläuterungen und Empfehlungen des Workshops Dokumentation und Veröffentlichung der Belastungseinstufung genetisch veränderter Versuchstiere am Bundesinstitut für Risikobewertung, Berlin 20–21 Juni 2013.
Volume 44, No. 1 | JANUARY 2015 31
