EUROPEAN COMMISSION Brussels, 8.11.2017 SWD(2017) 353 final COMMISSION STAFF WORKING DOCUMENT Accompanying the document REPORT FROM THE COMMISSION TO THE EUROPEAN PARLIAMENT, THE COUNCIL, THE EUROPEAN ECONOMIC AND SOCIAL COMMITTEE AND THE COMMITTEE OF THE REGIONS In accordance with Article 58 of Directive 2010/63/EU on the protection of animals used for scientific purposes {COM(2017) 631 final}



Annexes Annex 1: List of recommendations Annex 2: Report by EURL ECVAM



This Staff Working Document is in support of the Article 58 Review Report, and provides more detailed analysis of the different consultation activities and other information sources used for the Directive review. Executive Summary In view of the timing of the review, and the significant differences in starting points among Member States, many involved, whether from science, welfare or regulatory backgrounds, have as yet limited experience of the new measures set out in the Directive. It is too soon after transposition to evaluate the impact of the changes brought in with the Directive, and therefore, for this review to derive definitive conclusions. It can only provide indications on progress towards the Directive’s objectives, identify any common areas of difficulty, and some examples of good practice with the application of the new requirements which could be more widely applicable. The framework of the Directive is generally considered to be a sound foundation for the regulation of animals used in scientific research. There are significant differences in the ways in which some aspects of the Directive have been implemented in Member States, risking the main objectives of the Directive to deliver improved science and welfare and give a level playing field for the scientific community across the EU. That this is due either to a combination of incorrect transposition or how some aspects of the Directive have been implemented within the Member State is not clear in the responses of the respondents to the User and Stakeholder surveys. The impact of the Directive has varied among Member States. This has to a great extent been influenced by the legislative framework in place prior to transposition of Directive 2010/63/EU. In some Member States there have been few changes due to having, for example, considerable experience of project evaluation and authorisation processes, whereas others had no previous requirement, or formal structure in place for, project evaluation. It is not surprising therefore that views on the impact of the Directive vary significantly from country to country – this view was very evident in responses from the pan-European stakeholder organisations. There are some aspects which are developing and working well, for example Animal Welfare Bodies (AWB). The introduction of AWB is considered by the great majority of respondents to be a welcome addition, and these are already contributing positively to animal use and care practices within establishments. Other positive effects reported include raising standards in research practice, improved Three Rs awareness, promotion of culture of care, growing recognition within the research community of the link between animal welfare and good science, and increasing transparency. A number of areas have been identified where further progress is needed to meet the Directive objectives. Of these, project evaluation and authorisation processes are key to achieving a level playing field for operators within and between Member States. In some Member States, the introduction of formal project evaluation has significantly increased the work required to obtain an approval to use animals in research. There have also been delays to research due to the processes in place to secure some projects. These areas should be further scrutinised by Member States, where appropriate, to ensure that the processes implemented for project evaluation and authorisation are indeed effective, efficient and resulting in consistency in the outcomes. In addition, there may be a need for the development of further guidance on implementation or interpretation in some areas, or in some cases adjustments to be considered to the national legislative framework and guidance, to deliver the desired level playing field within and among Member States. Further harmonisation in approach is required to facilitate movement of staff and research programmes among Member States, to improve the National Committee role in promoting good practice and consistency, to improve quality of statistical reporting, for example reporting of genetically altered animals, and to improve quality and ease of access to current non-technical project summary publications, which may allay some concerns expressed by animal welfare groups on the perceived lack of transparency. Although a common understanding of education and training requirements has been achieved to a great extent, much work is needed to make this operate in practice to facilitate free movement of personnel. There needs to be increased efforts to improve awareness of available applicable alternatives - interpreted in its widest sense to include replacement, reduction and refinement of animal use -, and appropriate training and tools to facilitate their efficient use by all involved in the process. Even if not directly within the remit of this Directive, concerns were also raised about the need for development of more efficient processes to progress regulatory acceptance of alternative methods, and re-evaluation of validation processes to allow movement away from the need to use existing animal models as the gold standard. When improved animal welfare standards or practices for animals used for scientific purposes are identified and evidence based, Article 2 has been interpreted by some to prevent Member States from introducing these. The delegated powers foreseen within the Directive will enable delivery of these benefits across EU and therefore promote application of improved practices throughout EU.

The full envisaged benefits of the Directive will only be realised with effective national implementation and enforcement of the legislation. Without these, the objective of a level playing field of common standards and practices will not be achieved, there will be continued imbalances in standards of science and welfare, and confusion in public opinion, as standards among Member States will continue to differ. i. Introduction Directive 2010/63/EU on the protection of animals used for scientific purposes was adopted to provide for more detailed and equitable rules within Member States regarding the protection of animals used for experimental and other scientific purposes in order to reduce disparities by approximating the rules applicable in that area and to ensure a proper functioning of the internal market. To that end, it lays down rules on the following: a)The replacement and reduction of the use of animals in procedures and the refinement of the breeding, accommodation, care and use of animals in procedures; b)The origin, breeding, marking, care and accommodation and killing of animals; c)The operations of breeders, suppliers and users; d)The evaluation and authorisation of projects involving the use of animals in procedures. Member States were required to adopt national legislation transposing the Directive by the end of 2012 and the Directive took effect on 1 January 2013. i.i Purpose and structure of the Report Article 58 of the Directive requires the Commission to review this Directive by 10 November 2017, taking into account advancements in the development of alternative methods not entailing the use of animals, in particular of non-human primates, and to propose amendments, where appropriate. The review focuses on the three main objectives of the Directive, mainly to harmonise the legislation on the care and use of animals for scientific purposes to facilitate a level playing field for the operators; to ensure appropriate standards of welfare in line with Article 13 of TFEU through effective application of the Three Rs in the use, care and breeding of animals; and to improve transparency to the general public. Although there is some overlap in these objectives, and certain elements can impact on all three objectives, these are the general headings under which the main results are presented. i.ii Timing of the Review Although the provisions of the Directive entered into force on 1 January 2013, it was not until spring 2015 that the last transposition was completed. An important element of the Directive, namely common standards for accommodation and care, only entered into force on 1 January 2017. Conformity checks are ongoing, with a number of enquiries in progress. At this stage, there may be incomplete or inaccurate transpositions which will require changes to national legislation. Member State implementation reports are not due until 2018, and the EU implementation report until 2019. Projects started under the previous Directive can continue under transitional arrangements until the end of 2017. New authorisations are required from January 2018 at the latest, and the maximum length of a project is 5 years. Retrospective assessments of projects should be carried out after an appropriate time from the completion of a project. This may result in retrospective assessments being carried out a considerable time, e.g. 3 years, after the completion of a project. Only after January 2018 are all uses of animals covered by this Directive. The completion of 5-year projects authorised after January 2018 will take place in 2023. Subsequently, the true value of retrospective assessments can only be properly assessed after 2023, i.e. after sufficient experience of this process is attained. For these reasons, a review at this time is based on limited experience of the new provisions in the Directive by all those involved in the use, care and breeding of animals for scientific procedures, including regulators, scientific and care staff, and on opinions expressed or evidence presented by other stakeholders. ii. Consultation strategy and backgound information

Ii.i Stakeholder input Surveys Four structured questionnaires were developed to survey the experiences, interests and opinions of relevant stakeholders involved in the administration, implementation and functioning of the Directive. These were tailored to the major sectoral groups according to roles and interactions with the Directive and were distributed to: National Contact Points: All Member State National Contact Points were invited to submit national opinions on aspects of the operation of the Directive. Users, breeders and suppliers of animals (hereafter "user"): National Contact Points were asked to circulate the invitation to contribute to all establishments within their Member State. Each establishment, whether a user, a breeder or a supplier of animals, was invited to submit a single survey response representing the views of the establishment. The questionnaire focused on general views as well as on detailed elements of the Directive. Other stakeholders: Interested parties representing a range of animal welfare, science/academia, industry and veterinary stakeholders were invited to submit general views on the functioning of the Directive from their members/associated parties. The majority of invitations were to pan-European organisations with interests in the care and use of animals in scientific procedures, but contributions were also sought from national organisations concerned with animal welfare. Specific Three Rs stakeholders: As Article 58 of the Directive requires the review to be carried out paying particular attention to the availability of alternatives, an additional targeted questionnaire was prepared to seek some additional information concerning the development, validation and uptake of alternative approaches, specifically in the fields of basic, translational and applied research and in education and training. The questionnaire was sent to organisations specifically involved in these areas. In addition to presenting the distributions of views for each of the areas, a number of quotes from the surveys are included in this Staff Working Document. The purpose for their inclusion is to provide a representative sample of typical comments received for a given question and indicating the breadth of views expressed. Public Consultation An open consultation meeting was held in Brussels on 31st March 2017, to which all respondents to the four questionnaires were invited, and an open invitation was placed at the EC web-site. Presentations were given on the draft findings and attendees had the opportunity to raise comments and questions. These have been analysed, considered and incorporated into the relevant sections of the report, where appropriate ii.ii Other information sources SCHEER Opinion As the Article 58 Review of the Directive also required to take account, in particular, progress on the development of alternatives to the use of non-human primates, the Scientific Committee on Health, Environmental and Emerging Risks (SCHEER) was invited to review recent evidence to update the 2009 Opinion of the Scientific Committee on Health and Environmental Risks on “The need for non-human primates in biomedical research, production and testing of products and devices”. EURL ECVAM report Article 48 of the Directive refers to the EU Reference Laboratory, and Annex VII explains the duties of the laboratory. The EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) provided an update on the development and acceptance of alternatives to the use of live animals. The report is in Annex 2. Other Commission Communication in response to European Citizens' Initiative "Stop Vivisection" and the outcome of a subsequent Commission Scientific Conference "Non-animal approaches – the way forward". iii. Analysis of the responses to the consultations iii.i Limitations and interpretation of the results The consultation had serious limitations due to the early timing of the review and these were clearly confirmed by the responses. Depending on the topic and the respondent group, the proportion of responses that considered it being 'too early to assess' reached in some cases 43 - 47% of all responses. Interestingly, the area in which a significant proportion of measures have not yet come to effect (transparency), the level of responses stating it was too early to assess whether the Directive had improved transparency was only between 5-13% depending on stakeholder group. At a closer look, this can be explained by the 36% of the animal protection groups who disagreed, or strongly disagreed that the Directive had improved transparency.

Some of the questions in the questionnaires were open to interpretation, such as when selecting an answer "no impact" arising from a specific new measure in the Directive. This could mean that effective measures were already in place, or that the measures taken had not had the desired impact. Unfortunately, not all respondents qualified their responses. In some instances "changes" were reported, without the respondent further qualifying the nature of the change. iii.ii Background of the respondents Member States All 28 Member States responded to their questionnaire. User, breeder and supplier establishments Responses to the respective questionnaire were received from users in 25 Member States. A total of 889 responses were submitted, with distribution by Member States strongly skewed to France (34.4%), Italy (11.9%) and Germany (9.2%). Users in these three Member States submitted over 55% of all responses. No replies were received from users in Bulgaria, Cyprus or Malta. The table below provides responses by Member States (MS) and compares the number of replies with the number of AWBs in each Member State (as reported by Member State in their questionnaire). There are anomalies in the percentage of AWB responding with some Member State users providing up to twice the number of responses expected from the respective Member State data. On further enquiry, in a number of these cases, two or more responses were received from different facilities within a single large establishment (with one AWB). MS Number respondents % of total respondents No AWB* % AWB responding FR 306 34.42% 600 51.00% IT 106 11.92% 145 73.10% DE 82 9.22% 275 29.82% SK 47 5.29% 23 204.35% UK 47 5.29% 170 27.65% multi** 37 4.16% 0 SE 33 3.71% 40 82.50% BE 31 3.49% 300 10.33% NL 26 2.92% 70 37.14% AT 21 2.36% 40 52.50% ES 21 2.36% 244 8.61% PT 20 2.25% 20 100.00% HU 18 2.02% 35 51.43% RO 17 1.91% 40 42.50% DK 15 1.69% 45 33.33% CZ 14 1.57% 85 16.47% PL 14 1.57% 220 6.36% IE 9 1.01% 21 42.86% EL 8 0.90% 45 17.78% FI 7 0.79% 25 28.00% HR 6 0.67% 20 30.00% EE 5 0.56% 3 166.67% LT 3 0.34% 4 75.00% SI 3 0.34% 11 27.27% LV 2 0.22% 5 40.00% LU 1 0.11% 7 14.29% BG 0 0.00% 13 0.00% CY 0 0.00% 1 0.00% MT 0 0.00% 3 0.00% *from Member State questionnaire responses; assuming 1 AWB/establishment

** from users based in more than one Member State (including international) Since a single Member State (France) submitted over 34% of all responses, data have been analysed with and without the replies from users in France, and for the French responses alone. Where significant differences were noted, these are reported. To put these proportions above into perspective of the total use of animals in the EU, the use in France, Germany and UK together fluctuates between 55-60% of all animals used in the EU. Replies were received from 240 organisations in the private sector and 649 in the public sector. A total of 169 respondents (19%) identified themselves as an small and medium-sized enterprises (SME). For France, 107 (35%) were SMEs. Concerning areas of activity, 14 (2%) respondents were animal breeders and/or animal suppliers; some other responses also stated they bred and/or supplied animals as well but identified themselves as predominantly animal users. The vast majority, 757 (85%) represented animal users in science or academia. The breakdown of different industry sectors is below Industry sectors where applicable Sector No % Chemical industry (including consumer products, biocides and plant protection products) 8 1% Contract Research Organisation 38 4% Food- and feed sector 11 1% Other 13 1% Pharmaceutical industry (including both human and animal health) 120 13% Not specified 699 79% Total 889 100% Types of species used The majority of the respondents used rodents, but users of all the common laboratory species responded, including users of cephalopods. A few respondents did not identify any species of animal being used at their organisation. Stakeholder Organisations

52 stakeholder organisations responded to the questionnaire. Their distribution across sectors is indicated below The group "other" comprised of three Three Rs centres, two animal rights organisations and a European Animal Breeding organisation. The majority of organisations were European or international. However, to promote a balanced response, national animal welfare organisations, 16 of which participated, were also invited to contribute in addition to respondents from the user community, both at the establishment as well as at EU level. The Commission sought to reach out to all relevant stakeholder organisations at EU level. iv. General views Views by users and other stakeholders on three generic questions, namely on improvement of animal welfare, the quality and continuation of science, are presented here before addressing more detailed elements covered under the three key aims of the Directive. iv.i General impact of the Directive on standards of animal welfare, care and use of animals Respondents to the questionnaires were invited to consider whether the adoption and implementation of the Directive and the related national legislation had improved the standards of animal welfare, care and use in their country/region. The responses indicated that the revised regulatory framework is considered beneficial, in particular in Member States which did not have a comprehensive structure in place prior to the introduction of 2010/63/EU. User responses The adoption and implementation of the Directive and the related national legislation has improved the standards of animal welfare, care and use in my establishment. Users The majority of user responses agreed that already the Directive has already had a positive impact. Stakeholder responses The response from the stakeholder organisations was not as positive, with 13% of the view that more time was needed to assess the impact.



The adoption and implementation of the Directive and the related national legislation has improved the standards of animal welfare, care and use in my country/region. All stakeholders Other Stakeholder Organisations Animal Protection Organisations Separating the organisations involved in research from the animal protection organisations did identify a significant difference in their views. 75% of science/research organisations agreed that the Directive was improving standards whereas only 18% of welfare organisations were of this view and around 23% who considered it too early to assess. The main areas where improvements are expected are in the quality of authorised projects, education and training of scientists and care staff, housing and care practices, and implementation of the Three Rs. The importance of an effective AWB to deliver such benefits was emphasised by all stakeholders. Concerns were also expressed over lack of enforcement and the restrictions placed by Article 2 on the ability of Member States to introduce improved practices – knowledge of animal welfare needs is evolving rapidly, and Member States should be encouraged to adopt improved practices.

The following quote reflects many of those received from animal protection organisations: “The framework of the legislation is an improvement, but implementation and enforcement needs to be drastically improved for achievement of the Directive’s main goal to end the use of animals.” iv.ii Effect of the Directive on the quality of science The question given to the users and stakeholders concerned the impacts of the Directive on the quality of science through the application of new elements such as AWB, DV and a systematic project evaluation including harm-benefit assessment. A number of users make the comment that improved welfare contributes to improved science, including a reduction in stress, and improved health status reducing experimental variability. Many users, however, also point out that the quality of science generated in studies using animals is affected by many other factors outside the realms of the Directive. Others reflect on some of the factors that have been improved by the additional focus introduced by the Directive obligations such as on improved experimental designs leading to more robust and reproducible science, or more data or better quality data being available from the same number of animals by more appropriate designs and planning. The AWB has also helped standardisation of methodologies within establishments. The quality of science generated through animal studies is only partially dependent on the regulatory framework. However, the improvements in animal care and use standards and practices, including the required input to project design and evaluation, should be reflected in due course by improved quality of science, but it is too soon following transposition to provide specific evidence. The impact will again be dependent on the previous legislation, but the responses from users and scientific stakeholder organisations support the view that the introduction of e.g. AWB and a systematic project evaluation/authorisation have had a positive impact on model choice and design of procedures. Many animal protection organisations indicated that due to the lack of transparency generally so far seen across Member States during the implementation of the Directive, it is impossible for them to measure or assess any changes in ‘quality’ deriving from the Directive. User responses The Directive has improved the quality of science in my country/region through the application of new elements such as Animal Welfare Bodies, Designated Veterinarians and a systematic project evaluation. Users 40% agreed that the Directive had improved the quality of science, 18% disagreed. Of those who agreed, suggestions as to why this was the case included: ·AWB and Designated Veterinarians being mandatory in all animal facilities ·Systematic project evaluation ·Better staff training and competence ·Improved quality of monitoring of animals ·Further improvement in animal welfare and Three Rs leading to better science Of those who disagreed, for many, the processes were in place before under previous national legislation.

Other reported issues:

·"Animal Welfare Bodies and veterinarians have inadequate experience in assessment of animal welfare or quality of project in the case of some species such as Xenopus, Danio rerio." ·Some felt that the Directive would not affect scientific quality but that this was better “controlled” by scientists during peer review during the funding processes and of manuscripts submitted for publication. The point was made that the control systems must work together with researchers, as precluding valuable research work is not in the interests of anyone. ·"More interactions with vets and care staff, leading to benefits, such as new medication for post-surgery procedures, new methods for cleaning/maintaining animal wounds. Because animal stress is reduced and animal welfare is better, so scientific results are also better." ·"The facts that projects are now authorised based on the result of a favourable evaluation and that they are followed (from a 3Rs and animal welfare perspective) during implementation do not necessarily mean that quality of science has improved. But at least, processes are in place to make sure that the scientific approach is challenged and justified on a case-by-case basis." ·"The people performing the project evaluation lack the scientific competence necessary to improve the science in the project (many are not scientists or do not even have an academic background)" ·"Project evaluation is sometimes performed by people that do not know the study methods used which can cause difficulties to issue an opinion." Stakeholder responses The Directive has improved the quality of science in my country/region through the application of new elements such as Animal Welfare Bodies, Designated Veterinarians and a systematic project evaluation including harm-benefit assessment. All stakeholders Other stakeholder organisations Animal protection organisations Over a third of all respondents felt that it was too soon to be able to determine whether there had been any impacts. 36% of animal protection organisations did not agree that there had been any scientific improvements as a consequence of the different structures under the new Directive. Animal protection stakeholder comments ·"The lack of transparency in decision making, project applications and retrospective review makes it hard to answer this question." ·"Doubtful whether the new requirements improved quality of science. Looking at the NTPs and research projects we still have the impression that projects are licensed where independent cost-benefit analysis would indicate that they should not." ·"As the regulatory system does not allow for public oversight of project licence applications, the regulatory evaluation process or systematic publication of retrospective project evaluation and harm-benefit analysis, it is difficult to comment." ·"The increased emphasis brought by the Directive on the need for education and ongoing training of those using or caring for animals, and the need to ensure their competence, is welcomed." ·"Separation of authorisation and inspection functions in our country is not helpful" Particular concerns were expressed by an animal protection organisation in one Member State, where in their opinion no harm-benefit analysis is required prior to authorisation –

·“Authorities have to grant projects that have been formally correctly applied for.” Another response stated ·“The cornerstone of the regulatory system, the harm-benefit assessment, is, in the absence of useful EU law setting its operational parameters, a highly discretionary exercise on a complex issue. It is astonishing that the EC believes that a level-playing field could be created in these circumstances.” Other stakeholder comments ·"This might probably true for countries that did not have the mentioned bodies, experts or processes and still it is too early to have a clear picture if the quality has improved. or those countries that were already working as described in the Directive a change of quality cannot be seen, as it was already on a high level." ·"This question only refers to elements which have external control on research, ignoring the role of scientists themselves, arguably the most important factor for quality. Demanding more thorough external control will only be effective if scientists have knowledge and motivation to meet that demand. Good training in experimental design and analysis is essential to generate high quality science." ·"There are some areas where the quality of science will undoubtedly improve. For example, greater emphasis is being placed on good experimental design, which has scientific value, as well as welfare merits. In addition, increased sharing of good practice will improve the quality of science. However, we believe it is yet too early to appreciate the full scientific merit of the Directive." A number of Member States had much of the Directive framework in place, and it is not expected in these countries that significant improvements relating to the Directive transposition will be seen. In conclusion, it is clear from the responses that it is far too early following the transposition to be able to measure or assess the Directive impacts on the quality of science as it takes a number of years for e.g. publications to filter through. Furthermore, as stated, the quality of science is dependent on multiple factors, many of which are outside the scope of the Directive. iv.iii Continuation of high-quality research in the EU using animals, where still necessary Respondents were also invited to give views on whether or not the new Directive allows continued high quality animal research where necessary and justified. This statement was heavily criticised by the majority of animal protection stakeholder responses as wholly unsuitable as it implied that high quality research could be derived from animal studies. The animal protection stakeholder response also criticised the implementation of the new Directive, implying that the present regulatory and research environment also still allows badly designed or poorly carried out experiments to be funded, authorised and undertaken, which wastes animals’ lives and causes suffering that could have been avoided. From the scientific community, the responses related to differences in implementation, rather than failings in the Directive framework. The project authorisation process has introduced in many Member States additional robust requirements to justify the use of animals and requires implementation of the Three Rs. Concerns were expressed over the time taken to obtain project authorisation, but again this varied among Member States. There are different Member State approaches to the use of simplified processes (Article 42) and the processes/justifications required for exemptions to certain articles, for example animals taken from wild, care and accommodation, and authorisations for reuse and rehoming. Although there has been some closure and consolidation of user facilities in recent years, it is not possible to determine whether the increased bureaucracy indicated in some responses has been a contributory factor, rather the general financial situation and the increased availability of facilities in particular in Asia which are thought to be the major factors. User responses The Directive allows continued high quality research on animals where still necessary. Users Nearly 70% of users agreed that the Directive allows continued high-quality research on animals where still necessary. Only 5% disagreed. Even amongst some who agreed, the process has limited some research at their institutes. Several stated that they felt that delays to projects have been observed and several believe that this and other aspects of the Directive reduces or, if not improved, will reduce European competitiveness. Some stated that some scientists try to avoid doing animal experiments because of the administrative burden. Another stated that they felt that the persistence of some animal experiments was only because the scientists felt that their expertise lay with using those models (and not with alternatives). There have been some problems where single housing was required for experimental reasons, and for birds where a significant increase in pen size is required, an argument is made that these large enclosure sizes are not considered to be in the welfare interests of the birds. One stated that scientific experiments on Xenopus and Dario rerio were stopped due to over interpretation of the legislation in considering procedures and reuse.

Of those who disagreed, comments included ·"It discourages people from doing their research in Europe. There is a clear risk of people doing research outside this legal framework as it becomes more and more time consuming and ineffective." ·"The directive has many aspects that allow strong enemies of experimental research with animals to find arguments against these experiments and to stop them entirely. I believe (together with many colleagues who perform research in life sciences) that in the long-term Europe will lose competitiveness in research as compared to other regions in the world. The discrepancies in the quantity of regulation in comparison to agricultural use (economically justified???) is far too high," Other comments ·"Thanks to the Directive, we truly believe we perform high-quality research (see publications list) by keeping animal welfare as high as possible." ·"Research projects are now written and evaluated more accurately in all the phases before authorisation." Stakeholder responses 60% of responses agreed that the Directive allows high quality research using animals to continue, with 13% disagreeing.



"The Directive allows continued high quality research using animals, where still necessary, in my country/region". All stakeholders Other stakeholder organisations Animal protection organisations 36% of animal protection stakeholders and 87% of other stakeholders considered that the Directive allowed continued high-quality research animals, where necessary, to continue. The level of challenge to animal studies has increased, causing delays, but this is, in general, considered to have improved the quality of animal studies. The majority of responses acknowledge that the increased scrutiny towards the Three Rs, and animal welfare, accommodation and care has led to improvements in animal care and study design. However, caution is needed that the processes are efficient, without unnecessary bureaucracy, as there are concerns that certain types of research may stop or be relocated. The interpretation of the definition of “project” varies from a single procedure to a programme involving many different procedures. Applying for a project authorisation for each individual procedure is considered unnecessary and overly bureaucratic. The time taken for “minor” amendments was also noted as a concern, especially when the Directive requires only those amendments to be authorised that may negatively impact animal welfare. Animal protection groups expressed concerns over the structure of the question as being biased by implying that any animal research could be of high quality. Concerns remain over the justification for animal use, study design and analysis and implementation of the Three Rs. There is little evidence to date that the Directive has impacted animal numbers. Animal protection stakeholder comments included ·"This is a biased question. There are increasing concerns around the validity and translatability of many animal "models" and tests." ·"It is beyond dispute that it is business as usual, the numbers of animals used is rising, if anything, and much low-quality research continues to be carried out" ·"the present regulatory and research environment also still allows badly designed or poorly carried out experiments to be funded, licensed and undertaken, which wastes animals’ lives and causes suffering that could have been avoided."

Other stakeholder comments ·"The Directive allows competitive, high-quality scientific work that involves animals if no alternatives are available, without any major disruption of research, though short delays in delivering authorisations have occurred." ·"There remain significant challenges in terms of reproducibility and the quality of the design of animal experiments that the Directive has not tackled." ·"The increased scrutiny has provoked delays and cancellations in animal research, or transfers to other continents. It is difficult to evaluate the quality of research that did not take place." ·"The focus on experimental design and methodology has impacted positively. Many elements are positive but issues still exist with statistical reporting and definition of project." Section 1 - Harmonisation of legislation i Introduction A key aim of the Directive was to create a level playing field for all of those using animals in research and industry, and for any others impacted by that use, through harmonisation of legislation and its objectives and outcomes. There seems to be some confusion, especially among users, over whether or not uniform operational practices could be expected as the result of the new Directive. However, Member States have the sovereignty to determine how best to achieve the objectives through national legislation, operational procedures and practices. A number of aspects were included in the legislative framework, which are aimed at progressing the harmonisation process. These included modifications to the scope, education and training requirements, common criteria and conditions for project evaluation and authorisation, and through Article 2 the limitations on unilateral changes to adversely affect the internal market. Although the impacts of the Directive cannot yet be fully determined or analysed, the responses from scientific and animal protection stakeholders are suggestive that the interpretation and implementation varies so significantly across, and even within, Member States, the Directive will not quickly deliver the desired level-playing field. Many examples were provided where different practices exist. ·“There are different interpretations and level of enforcement by the sometimes disaggregated (at regional/provincial level) competent authorities with different knowledge, resources and commitment: the level of control differs significantly (response to project authorization varies a lot, many projects in some countries are pending).” ·“There still is a major lack of harmonisation especially due to different interpretation of the Directive during harmonising the local laws and regulations. Countries still do not allow execution of animal experiments if these were evaluated and accepted in foreign countries. Also the education is not always accepted from country to country, due to local laws.” ·“The Directive can be seen as the foundation for a common level playing field and indeed a certain degree of harmonisation has occurred especially in standards - but authorisation and administrative processes seem to differ which is leading to uncertainty by the applicants.” ·“The Directive has the potential to level the playing field, however problems exist around its implementation. There are signs of disparity in project evaluation and authorisation between member states; e.g. primate neurology experiments which were not authorised in one MS on severity grounds were allowed in another.” Directives do not set out required processes or structures, unlike regulations, but there are concerns that the different structures which have evolved, in particular for project evaluation and authorisation, may not deliver common outcomes. Although some progress is being made towards common structures, which has been acknowledged by many users, without some discussion and willingness among Member States to improve harmonisation of outcomes, it is considered unlikely that the desired level playing field will be fully realised. Responses from some Member States acknowledged that ensuring a consistent approach to project evaluation and authorisation was still being progressed and that further guidance on the process, including the framework for and composition of evaluation review groups/bodies was still under development. National Committees are not sufficiently well established to have progressed their role in ensuring a coherent approach to project evaluation and sharing of best practice. The requirements for project evaluation and authorisation have caused concerns over additional bureaucracy, delays and costs for scientists among users and some stakeholder organisations. Some users raised concerns over inconsistencies between evaluators/evaluations within the same Member State, and over inconsistencies between Member States on authorisations issued. In contrast, around one third of the user respondents were of the view that the Directive had already created a level playing field. A key advantage was considered to be the harmonisation of animal care and accommodation practices. Even though these were only mandated in January 2017, the introduction of such changes is known to have commenced prior to this date.

Of those who did not indicate that the Directive was progressing harmonisation, some stated that there was divergence in the application and interpretation of the Directive at national, regional or local levels. It was suggested that different financial resources within the different Member States may be affecting development of a level playing field. It was felt by some that this was putting those who had fully implemented the Directive at a competitive disadvantage. Others commented that there are differences in other parts of the world which can influence the EU work, including different (lower) housing requirements, which put higher constraints on EU competitiveness. ii General views on harmonisation objective User responses "The Directive has created a level playing field by providing similar conditions for operators, irrespective of their country or region." Users One third of the users were of the view that the Directive had created a level playing field. 15% disagreed. 13% said it was too early to say. The key advantages were harmonising of animal housing and procedures, particularly seen amongst those working in several different countries. Of those who disagreed, some stated that there was divergence in application / interpretation of the Directive at National or local levels, and some had not seen harmonisation. There may be more standardisation in animal care than in the protocols. For some, not all the processes are available yet (simplified administrative procedure and multiple generic projects). Comments ·"I have been working in the UK, Denmark and France. Conditions are very different between these countries" ·"Whereas the housing and care standards are very similar across different user establishments, the implementation of other aspects such as project review and authorization still differs a lot between countries and institutions." ·"In this matter, the key point is now more the potential discrepancies between the requirements enforced in EU regarding animal research vs when performed in third party countries (e.g. EMA, or North America to a lesser extent) : i.e. some protocols may be outsourced overseas." ·"Since many details of Directive 2010/63/EU are unclear and our country so far has not set up implementation rules, there are enormous disharmonies even between different regions. We further do not have the impression that other countries adopted Directive 2010/63/EU as stringently as we have." ·"Still very hard to get cross-border agreement on required training for those carrying out scientific procedures" ·"The intrinsically logical structure of the Directive came out distorted by just adapting the old law rather than renewing it. There is no level playing field and our establishments are already exporting their work to neighbouring countries." Stakeholder responses 29% of organisations are of the view that the Directive has made progress towards a level playing field, with 32% disagreeing with this view.



The Directive has created a level playing field by providing similar conditions for operators, irrespective of their region or country. All stakeholders Other stakeholder organisations Animal protection organisations

There are significantly differing views between the animal protection organisations and the other (mainly scientific) stakeholder groups - 36% vs 24% agree and 18% vs 50% disagree over progress towards a level playing field. The main areas of concern identified by the other stakeholder groups included PE processes, size and complexity of projects, inconsistencies within different regions of individual Member State (far less across EU), different authorities being required for the same/identical projects in different Member States, and the time taken to obtain authorisations (from initial application). There remain differing requirements for education, despite agreement on a common framework, continuing the difficulties for personnel moving between Member States. The animal protection stakeholders acknowledged that progress is being made towards a level playing field as intended by the Directive framework, but there are differences in implementation processes and rates, and effectiveness of implementation, making it difficult to predict whether this will be fully achieved. Different authorities are imposing different controls – for example some projects not permitted in one Member State are permitted in another. The main concern from the animal protection stakeholders is over the view that Article 2 hinders progress on animal welfare, preventing Member States adopting improved standards.

Animal protection stakeholder comments ·"The text of Directive encourages harmonisation, however a major problem exists around its proper and consistent implementation." ·"We disagree with the premise of Article 2 as it hinders progress on animal welfare and MS should be allowed to raise animal welfare standards." ·"The cornerstone of the regulatory system, the harm-benefit assessment, is, in the absence of useful EU law setting its operational parameters, a highly discretionary exercise on a complex issue. It is astonishing that the EC believes that a level-playing field could be created in these circumstances" Other stakeholder comments ·"The Directive has created the means for a level playing field, however in practice differences exist in implementation between Member States. The inconsistency in implementation which create most uncertainty for industry are in the authorisation procedures." ·"The problem is with implementation, not with the text itself. However, a degree of harmonization was achieved through alignment of severity criteria, transparency measures, and animal welfare bodies, and an increase in husbandry and housing standards. Most divergences are in the authorization and other administrative procedures (requirements for personnel)." ·"There are still many differences in harmonisation / implementation at country\regional level. One of the key areas of concern for private and public research lies in slowness of the authorisation process." ·"There are different interpretations and level of enforcement by the sometimes disaggregated (at regional/provincial level) competent authorities with different knowledge, resources and commitment. 1.1 Project Evaluation and Authorisation (Articles 36-42, 44) Project evaluation and authorisation are central pillars of the new regulatory system, and consistency and efficiency in process and outcomes are essential to deliver a level playing field for the scientific community and consistently deliver the desired welfare and scientific benefits. The requirements for project applications are set out in Article 37 and Annex VI. The requirements for verification of the content of the applications and considerations for project evaluation are laid out in Article 38. The requirements for project authorisations issued by the competent authority are described in Articles 40 and 41. Both the project evaluation and project authorisation must be carried out by a competent authority (Article 36) and with a degree of detail appropriate for the type of project (Article 38(1)). Furthermore, the project evaluation should be performed in an impartial manner and it may integrate the opinion of independent parties (Article 38(4)). Specific guidance has been produced to assist in the development of these processes. The greater majority of Member States have disseminated the EU Guidance on Project Evaluation, although some only recently. However, it was not clear from the responses if project evaluators have received it or if they are using it. 1.1.1 Project evaluation (Article 36 and 38)

In many Member States, a project evaluation and authorisation processes were in place under previous legislation, but the detailed requirements have changed under the new Directive. There are now clear requirements for what is expected to be included in the application for authorisation (Articles 37, 38 and Annex VI). The project evaluators verify that constraints set by the Directive are complied with, for example restrictions on use of non-human primates and use of endangered species, evaluate its objectives and compliance with the Three Rs and the expected harms. Finally, with all necessary information, the evaluators need to determine whether on balance the benefits are likely to be achieved and that they outweigh the expected harms. Projects may not be authorised unless this is the case. Across the 28 Member States a number of differing structures have been developed to meet these requirements. In some Member States, a single competent authority/committee considers applications from the entire country, perform project evaluation and, where appropriate, project authorisation. In others, there are regional committees, or committees within user establishments, often integrated with the AWB. There are differing challenges, dependent on the structure, to meet the various requirements set out in the Directive for project evaluation and project authorisation, including, in particular, impartiality, proportionality and consistency. With project evaluation at a national level, additional information may be required on the quality of the facilities and availability of experienced staff within the establishment in which the work will be performed. This information is needed to assess the likelihood of success as part of the harm-benefit analysis and thus requires input from a local perspective. However, dealing with applications at the local level raises questions over impartiality. At a local level, there will also necessarily be a greater number of project evaluation committees which poses additional challenges to ensure a consistent outcome, one of the key aspects of creating a level playing field. The fewer the number of committees/evaluators, the easier it is to achieve consistency – however, currently the number of committees/evaluators range from 1 to around 125 (within a single Member State). The EU Guidance details some of the pros and cons of the different approaches. Both users and stakeholder organisations have identified the varied implementation strategies as a significant risk to the attainment of a level playing field. European stakeholder organisations noted significant differences in the contributions from individual Member State constituent organisations (e.g. AFSTAL/LASA to FELASA). Comments included ·"We do note however that the Directive has placed an additional burden on companies during their assessment of a project, and that EU guidance has been lacking or is insufficiently known to users or in cases not applied by authorities. Moreover, this resource is not accessible and/or available in all official languages. A concrete example, informs us that the template is not always possible to complete with the relevant information and in an accessible manner. Overall it is our assessment that the Directive will need to be applied more widely across EU Member States if it is to have a more significant impact, and hereby improve animal welfare on a larger scale. For this reason, there are elements relating to evaluation and authorization that are too early to definitively assess." ·"The multiplication of project reviewing entities in some countries (National Committee+local committees) cause bureaucracy and delays." ·"The requirements to explain more clearly the harms to animals and information on the 3Rs complemented with the individual animal severity assessment have already had an impact on planning and executing studies and on consideration for animal welfare. However, the system needs to be worked out and time is required to settle down properly and not being considered as purely administrative burden." Detailed information on the project evaluation and retrospective assessment processes were not provided by Member States for this review, but these will be submitted by Member States in 2018 to form part of the Commission implementation report due by November 2019. Half of the users considered that the processes of project evaluation and authorisation were effective and efficient. However, users and stakeholder organisations have reported the existence of inefficiencies or ineffectiveness of the project evaluation and authorisation processes in many, if not all countries. It should be noted that the timing of the review is such that many scientists have yet to submit a project application and are still using authorisations issued under previous legislation. For some users, particularly in some Member States, the level of scrutiny and the delays caused have been detrimental to scientific output. Such delays do not occur in all Member States but processes in others may require some adjustment to allow progress to be made. It is clear from the user responses that for some applicants, the understanding of the requirements for the application submission, and of the processes for project evaluation and authorisation are not ideal. There were also concerns raised about duplication in the processes - in some circumstances, review by up to three separate committees - and in the content required to be submitted in project applications. Information that it is in excess of that required by the Directive seemed to be requested by some evaluators, and there were reported inconsistencies between what the establishment internally asks and what the competent authority requires. Some of the delays and inconsistencies were reported to be due to insufficient or inexperienced staff who are undertaking project evaluation. Independence of the evaluation process was questioned when evaluation was carried out within the establishment.. Multiple generic projects and the simple administrative processes (both measures designed to simplify processes and reduce bureaucracy) have not been utilised extensively, indeed many user responses suggested that neither was available nor indeed understood. However, where a simplified process is available and known about, two-thirds of the users stated that there was an improvement in administrative savings or processing times with regards to these project types after the implementation of the Directive. These responses did however highlight the different approaches taken by Member States towards the nature, size and complexity of projects. This seems to vary essentially from a project containing a single procedure involving a few animals of one species to a project for a five-year programme of work involving multiple procedures and species and many thousands of animals. Although both approaches to authorisations are acceptable, such differences in approach are raising concerns and difficulties when studies or projects are required in more than one Member State or when a project is being transferred from one Member State to another. Amendments to projects already authorised were discussed only by a few consultation respondents, probably due to limited experience of such measures. Users requested greater efficiency in evaluation and approval of amendments. The requirement by a few Member States to require changes to projects before researchers can implement improvements to the application of the Three Rs causes frustration within the scientific and welfare community and delays implementation of welfare improvements. This may also exceed the requirements of Article 44. Member State responses When project evaluation and authorisation processes were introduced under the new Directive, were the previous processes critically reviewed to optimise the efficiency and effectiveness of administrative processes?

Yes 18/28 No 6/28 Not applicable 4/28 The majority of Member States indicated that during the implementation of the new Directive, the opportunity was taken to optimise the efficiency and effectiveness of the administrative processes around the project authorisation processes. The revised processes included revised project application forms and processes, and simplified handling of minor amendments. Electronic submission and documentation have improved efficiency in some Member States. Some concern was expressed by one Member State on the costs of implementing the project evaluation and authorisation process. Has the task of project evaluation be assigned to a Competent Authority other than a public authority in your Member State? No 17/28 Yes 11/28 There are significant differences among Member States with regard to the project evaluation and authorisation processes. The systems seem to vary from evaluation and authorisation at local ethical committees to a single national committee looking at all proposals within the Member State. The number of committees ranges from 1-125. Both users and stakeholder organisations have identified the varied implementation strategies as a significant risk to the development of a level playing field. User responses Are the processes of project evaluation and authorisation effective and efficient? Please consider also processes required for amendments and renewals? 46% of user responses indicated satisfaction over the project evaluation and authorisation processes. The majority of concerns were over the time taken to obtain project authorisation. Despite guidance on applications, applicants found it difficult to submit the necessary information to the competent authority. There remain some teething problems in Member States where electronic submissions have been introduced. Some concerns were expressed over the lack of (numbers and experience) staff at the competent authority to deal with applications. Inconsistency within the project evaluation process was highlighted, in particular where multiple competent authorities and review groups were involved within Member States, and between Member States with different processes. ·"With the new requirements, the process is less efficient and has increased the administrative burden on users." ·"Provide a reduced project application to facilitate Pilot studies using only few animals – full project application is unduly onerous for a project which may not be required if initial pilot fails." ·"The main impact is very high administrative load (and cost). In our view systematic project evaluation is unnecessary and redundant in many aspects with other procedures. In our view, what should be evaluated once until significant modification occurs are the protocols and procedures. Projects that are submitted for funding should indicate whether protocols are approved. The local animal welfare committee should have the autonomy to approve projects."

·"More complex situation and additional burden when evaluation at the procedure level, which already existed in our establishment before the Directive, changed to evaluation at the project level" EU Guidance on project evaluation Member State responses Has the developed EU guidance been disseminated and used by those carrying out project evaluations? Yes 25/28 No 3/28 Where no, this was due to a delayed dissemination until national language versions were made available. Has the developed EU guidance been of benefit to those carrying out project evaluations? Yes 16/28 Too early 6/28 No opinion 1/28 No response submitted 5/28 Generally well-received by project evaluators to assist the process and to promote a harmonised, consistent approach but some are still evaluating the benefits of the current documents. Has any training been established for Project Evaluators as a result of the developed EU guidance on Project Evaluation and on Education and Training Framework (including training module for project evaluators)? No 22/28 Yes 6/28

Where training has been provided, benefits were noted in terms of the analysis undertaken regarding animal welfare, scientific value, statistical design, severity assessment and consistency of approach. Stakeholder responses stressed the importance of trained evaluators to ensure an informed and consistent process. User responses Are you aware of the guidance developed in the EU by Member States and stakeholders to facilitate the common understanding and implementation of the Directive? All users France Rest of EU No % No % No % No 273 31% 144 47% 129 22% Yes 616 69% 162 53% 454 78% Total responses 889 100% 306 100% 583 100% Further dissemination of the developed guidance would be beneficial. Some additional comments on guidance is summarised below: ·There may be scope to improve the guidance as some find them difficult to understand. Comments were received stating that the guidance was too long, whereas others requested more content. ·The role and tasks of the Designated Veterinarian may not be sufficiently clear in some countries, such that excessive costs are seen to be incurred. ·More species-specific information is requested e.g. for fish. ·Improvements in consistency in consideration of the same procedure in different countries were requested. Has the developed EU guidance been helpful to those preparing project proposals? The guidance was generally considered helpful. A number of users were unaware of the guidance, and others did not have access to translated versions. Some comments on concerns included: ·"Examples of PE would be helpful – in particular in determining the level of detail and proportionality of the evaluation processes." ·"Clarification is needed to interpret the conditions for reuse in a uniform manner." 1.1.2 Multiple generic projects (Article 40)

Article 40 allows Member States to authorise multiple generic projects carried out by the same user if such projects are to satisfy regulatory requirements or if such projects use animals for production or diagnostic purposes with established methods. Member State responses Is authorisation of multiple generic projects in Article 40(4) allowed in your Member State? No 8/28 Yes 20/28 Have preliminary benefits been observed in terms of any administrative savings or processing timelines for respective competent authorities from multiple generic projects? It was stated to be too early to assess as only a few projects will have been approved under this article. Some indication of a reduction in administration was identified by a few, but others were of the opposite view and suggested the level of administration required by applicant/establishment is not reduced. Some Member States indicated that the possibility was already available under previous legislation. In one Member State, an additional request for regular progress reports and summary of animal use has been introduced for such projects. User responses If an authorisation of multiple generic projects is allowed in your country (Article 40), is it used by your establishment? Most report that this is not allowed. Examples where it is used include maintenance of parasite cycles, regulatory toxicology and breeding of genetically altered animals. Have preliminary benefits been observed from authorisation of multiple generic projects in terms of any administrative savings or processing timelines for your establishment? Only few comments were received, but one example indicated significantly reduced administration where it has replaced individual authorisations for regulatory toxicology work (1 versus 100 projects). 1.1.3 Simplified administrative procedure (Article 42) Article 42 allows Member States to introduce a simplified administrative procedure for projects containing procedures classified as non-recovery, mild or moderate and not using non-human primates, and that are necessary to satisfy regulatory requirements or which use animals for production or diagnostic purposes with established methods.

Member State responses Is simplified administrative procedure in Article 42 allowed in your Member State? Yes 14/28 No 14/28 In response to whether preliminary benefits had been observed in terms of any administrative savings or processing timelines for respective competent authorities from simplified administrative procedure, only few benefits had been perceived, including the waiving of the non-technical project summary. User responses If a simplified administrative procedure (Article 42) is allowed in your country (projects to satisfy regulatory requirements with no severe procedures and not using non-human primates), is it used by your establishment? Have preliminary benefits been observed from simplified administrative procedure in terms of any administrative savings or processing timelines for your establishment? There may be some misinterpretation of these questions. Some responses appear to be discussing changes in administrative procedures such as moving to electronic systems. Some respondents from countries without simplified systems reported that they used them. Simplified procedures are not always available where repeat and standardised studies are required for regulatory reasons. An individual submission for each is still required by some Member States. In conclusion, the term "simplified administrative procedure" does not seem to be clearly understood. Half of the Member States have not adopted this measure and some users in countries without the possibility for a simplified administrative procedure think that they use these. 1.1.4 Authorisation decisions (Article 41) Article 41 sets deadlines within which both project evaluation and project authorisation processes should be completed and communicated to the applicant. However, these timelines must be counted from the receipt of the complete and correct application. Half of the users replied that the decisions on projects were communicated within the required maximum timelines. However, there were several responses stating that the process takes too long, outside the required 40/55 days, with some taking up to several months. It was reported that to deliver a “complete and correct” application can involve lengthy negotiations with the regulator, before the 40-55 days begin. Therefore, clarification on how the days were calculated was requested by some. In some Member States, a “stop/start” clock system is used to determine the time taken to consider the application – that is, at each stage of the process when a draft application is under consideration by the evaluators the clock is running: when it is returned to the applicant the clock stops. The different accounting systems can make significant differences as to whether or not the Member State achieves the targets set in Article 41, but does not necessarily reflect the application to authorisation time for the scientist. For some, times for obtaining authorisations are holding up staff and / or science. Some problems were reported over some electronic submission systems at the time of the consultation. A number of Member States have introduced financial charges for projects. Concerns were raised that, despite paying for the service, the time-lines set out for authorisation decisions in Article 41 were not met. User responses

Are authorisation decisions (Article 41) taken and communicated to project applicants within the timeframes (40 working days with a possibility to extend by 15 working days for complex projects)? Of those who responded, almost half considered that the authorisation was not communicated within the required timelines. Further examination of this question revealed that there was a significant difference between the responses from users in France and those from other Member States, with 74% of responses from France indicating that authorisation dates were not communicated within the 40/55 days set out in the Directive, compared with 32% elsewhere. All users France Rest of EU No % No % No % No 327 47% 190 74% 137 32% Yes 364 53% 68 26% 296 68% Total responses 691 100% 258 100% 433 100% A significant amount of frustration was conveyed in the comments, a small selection of which are included below: ·"We are a CRO, our sponsors contact us when they need and do not want to wait first 40 (+15) days prior to initiation of a study. They may find help in other countries outside EU." ·"Clarify what is needed for ethical evaluation. lot of variation in evaluation from one ethical committee to another." ·"Dedicate specific resources for ethical evaluation." ·"Ask the authorizing body!! They don't work in time but ask money for it!" ·"On the whole most applications are returned within 40 working days. However application/interpretation of how to use the 40 working days has led to significant delays with the processing of some licences." ·"No. However, this depends on the definition as to when the 40 days start. The total loop hole on when the “40 days starts" is ridiculous. (The definition of complete and correct application). What’s the point of sending letters saying it, when applicants don't get their project even looked at for 4-6 months. When the CA is recruiting/training new Evaluators it should have been more efficient and recruit a few spare as you'll be in the same position soon for sure. The burden the current evaluators are under is immense." ·"Improve national project evaluation process, reduce response times, increase body of inspector or have a EU / Brussels based analysis of projects system" Increased resource for project evaluation is requested. Improved training by competent authority for applicants and evaluators to explain requirements would be helpful. Consistency needs to be improved as significant regional variation was reported impacting on ability to meet scientific/sponsor deadlines. 1.1.5 Role of National Committees (Article 49) Recital 48 and Article 49 lays out the purpose and the tasks of the National Committee with regard to project evaluation i.e. to ensure a coherent approach to, and share best practice on project evaluation. Less than one quarter of the users considered that the National Committee had been effective in promoting a coherent approach, perhaps understandably as many are not yet well established. As the majority are only in the early stages of development, there appears to have been little activity to date on sharing best practice on project evaluation. This is an aspect of their work which, if effective, would improve confidence in the project evaluation process.

Member State responses Has the National Committee (Article 49) been effective in ensuring a harmonised approach to project evaluation and harm-benefit assessment by different competent authorities (when more than one) throughout the country? Yes 7/28 No 3/28 No opinion / NA 8/28 Too early to assess 10/28 Among the contributions made by Member States are promoting standardisation of the approach to project evaluation with an agreed template and producing guidance on the functions of project evaluation committees. Examples were also provided of joint membership of, or observer status at project evaluation committee(s). Advice also provided to remind project holders of obligations to apply the Three Rs throughout the lifetime of project. User responses Users were invited to consider the impact of the introduction of National Committee in promoting a consistent approach to project evaluation, and on their effectiveness in supporting AWB. Has the National Committee (Article 49) been effective in promoting a coherent approach to project evaluation and level playing field? There were significant variations in responses, again reflecting the structures in place under earlier national legislation and the speed of progress with the implementation of the 2010 Directive. Inconsistencies among project evaluators within the same Member State were cited as concerns. For example ·"Different regions not applying always the same criteria. However, they work on it." ·"Too many discrepancies among ethical committees." Recommendations ØThe Commission services and Member States should engage in discussions to improve guidance and provide further examples for the scientific community on what constitutes a "project". ØMember States should review if additional administrative gains could be attained for authorities and operators from a wider use of multiple generic project authorisation and simplified administrative procedures. ØWhere lacking, Member States should provide clear guidance on the required content for a project application, review that the requested elements directly relate to the performance of the harm-benefit assessment in line with Article 38, and that the level of detail is appropriate for the type of project. ØMember States should engage with relevant stakeholders to review their respective project evaluation and authorisation processes to identify any duplication and to establish measures of simplification aimed at efficient, effective and timely processing of applications. ØTraining for both project applicants and project evaluators would seem beneficial. Joint efforts by the Commission services, Member States and other stakeholders should be made to create opportunities for such training. ØUrgent focus is needed by National Committees on their key task to establish a coherent approach to project evaluation in particular in Member States with multiple competent authorities tasked with project evaluation. The Commission services, Member States and National Committees should engage in discussions to develop appropriate tools for this purpose. 1.2 Changes in Scope of Directive (Articles 1 and 5) Under the previous Directive 86/609/EC and transposed Member State legislation, there were countries who extended legislative protection to certain other specified types of animals, animals at various stages of development and types of work using animals. These inclusions were reviewed during the development of 2010/63/EU, and the scope revised to include those which were justified on scientific and welfare grounds, to promote harmonisation and afford additional welfare protection.

1.2.1 Inclusion of cephalopods (Article 1) Only few users and four Member States reported use of cephalopods. In one Member State, cephalopods were protected already under the previous legislation. For scientists in other Member States, it was reported that the administration has slightly increased. The European Cephalopod Research Association (EuroCeph) submitted a response providing an update on issues relating to cephalopod research. EuroCeph noted that in their experience regulation is having a positive effect in EU and abroad by creating a culture of care for this taxon. The degree of development of knowledge on the adequate conditions for the maintenance and care of cephalopods in captive conditions is still relatively low, and for many species in its infancy. Neither Annex III (Care and accommodation) nor IV (Methods of killing) contains specific guidance on cephalopods. Since the adoption of the Directive EuroCeph has invested significant efforts to fill this gap. Once sufficient evidence is available, the necessary amendments to the respective annexes should be made to ensure EU wide application. 1.2.2 Foetal forms of mammals in the last third of normal development (Article 1) Foetal forms were already protected in many Member States, but not in all. Where this was a new requirement, responses from eight Member States cited increased administration with little evidence to date of improved welfare or science. Member State responses Has the inclusion of foetal forms of mammalian species under the scope of the Directive had an impact in terms of administration, quality of science and animal welfare? Impact on administration Yes 8/28 No 10/28 No view/NA 4/28 Too early to assess 6/28 Impact on quality of science Yes 5/28 No 6/28 No view/NA 7/28 Too early to assess 10/28



Impact on animal welfare Yes 8/28 No 5/28 No view/NA 6/28 Too early to assess 9/28 User responses Is your organisation using foetal forms of mammalian species? No % No 641 72% Yes 248 28% Total responses 889 100%

Has the inclusion of foetal forms of mammalian species under the scope of the Directive had an impact in terms of administration, quality of science and animal welfare? Impact on administration No % No 88 35% Yes 117 47% Too early 26 10% No view/NA 17 7% Total responses 248 100% Impact on quality of science No % No 153 62% Yes 37 15% Too early 43 17% No view/NA 15 6% Total responses 248 100% Impact on animal welfare No % No 134 54% Yes 63 25% Too early 35 14% No view/NA 16 6% Total responses 248 100% Most comments reflected on increased administration. A few suggested that greater thought, planning and oversight had improved science and welfare. However, in general it was not considered to have improved science. The addition of killing methods specific for foetal forms in Annex IV was requested. 1.2.3 Animals used for the purposes of education and training (Article 5) Article 5 which sets out the purposes for which procedures can be performed in the EU includes animals used in higher education, or training for the acquisition, maintenance or improvement of vocational skills. Using animals in scientific procedures for educational purposes in schools was controversial and new provisions exclude lower education establishment from using them. Project authorisation is now required for use of animals in higher education and training in vocational skills. Similar provisions were already in place in many Member States, but not in all. Changes were generally, but not entirely, considered beneficial, in terms of refinement of and reduction in animal use. One Member State expressed disappointment that in their view the quality of teaching in schools has been reduced. Member State responses Has the inclusion of animals used for education and training under the scope of the Directive had an impact in terms of administration, quality of teaching and animal welfare? Impact on administration Yes 8/28 No 13/28 No view/NA 4/28 Too early to assess 3/28 Impact on quality of teaching Yes 6/28 No 14/28 No view/NA 4/28 Too early to assess 4/28

Impact on animal welfare Yes 10/28 No 12/28 No view/NA 4/28 Too early to assess 2/28 User responses Is your organisation using animals for the purposes of education and training? No % No 496 56% Yes 393 44% Has the inclusion of animals used for education and training under the scope of the Directive had an impact in terms of administration, quality of teaching and animal welfare? Impact on administration No % No 133 34% Yes 202 51% Too early 31 8% No opinion/NA 27 7% Total responses 393 100% Impact on quality of teaching No % No 166 42% Yes 178 45% Too early 28 7% No opinion/NA 21 5% Total responses 393 100% Impact on animal welfare No % No 188 48% Yes 161 41% Too early 29 7% No opinion/NA 15 4% Total responses 393 100% Where use of animals for educational and training purposes was not previously included in national legislation, then comments indicate an increase in administrative burden but also acknowledges greater consideration for such use thus benefiting positively animal welfare. Some impact was noted on reduction by greater use of individual animal tissues, for example by sharing among research groups. One response stated that more animals were required to train people as local authorities ask for specific courses in addition to (adequate) training in university courses. Another response suggested this change has had a very negative consequence: ·“one training for experimental surgery using only alternative methods (like inert models, ...) has been approved in my country and as a consequence all other training applications which still used animals have been rejected. In my opinion using plastic models or animals for the training of surgery certainly does not give the same training quality. This is a threat for the welfare of animals/patients undergoing subsequent surgery by the diplomates.”





Other comments included: · “formal recording of training and competency in a central database has been a very effective means of verifying the competency of researchers and ensuring compliance” ·“The creation of a High-Tech simulation platform allowed to replace many exercises in vivo and develop more practical curriculum, thereby increasing the quality of teaching.” ·“One new aspect is the retrospective assessment of individual animal severity. This has the potential to be used for learning and further implementation of 3Rs generally.” ·“we re-evaluated the number of animals needed to master techniques. Students work in pairs and make optimal use of the animals to learn the most techniques possible per week and we harvest skin (for suturing techniques) and many organs that serve as base materials for other courses (e.g. histology)." 1.2.4 Animals used for the purposes of routine production (Article 5) The use of animals in routine production, such as blood harvest, was already covered in the vast majority of Member States under previous legislation. Most Member State responses state no impact since the introduction of the Directive. User Responses Is your establishment using animals for the purposes of routine production such as for blood based products? No % No 792 89% Yes 97 11% Total responses 889 100% Has the inclusion of animals used for routine production under the scope of the Directive had an impact in terms of administration, quality of science and animal welfare? Impact on administration No % No 42 43% Yes 40 41% Too early 5 5% No opinion/NA 10 10% Total responses 97 100% Impact on quality of science No % No 56 58% Yes 27 28% Too early 6 6% No opinion/NA 8 8% Total responses 97 100% Impact on animal welfare No % No 51 53% Yes 35 36% Too early 5 5% No opinion/NA 6 6% Total responses 97 100%

The majority of users were already used to previous legislation and did not see any impact. Where introduced in a Member State for the first time, there were some reports that timely authorisation processes do not always occur and concerns were expressed on delays getting authorisation in commercial environment - highlighting the issue stated earlier on differences in size and complexity of “projects”, from individual procedure to complex 5 year programme with multiple procedures. There is scope for a wider use of multiple generic projects and/or a simplified administrative procedure for these types of projects. Some expressed benefits of greater consideration for animal welfare, with standardised accommodation and care and more refined procedures in the area of routine production. Recommendations ØFurther guidance should be developed to improve clarity on the minimum threshold of severity needed to bring a procedure under the scope of the Directive. ØThe European Commission should propose amendments to Annexes III and IV for cephalopods once sufficient evidence is available. ØThe European Commission should consider incorporating appropriate killing methods for foetal forms of mammalian species in Annex IV and review whether methods already contained in the Annex are still in line with the latest scientific knowledge. 1.3 Education and training of staff (Article 23) Requirements for education, training and competence of staff are described in Article 23 and Annex V of the Directive. As a new element, the Directive has paid particular attention to acquisition, demonstration and maintenance of competence. Free movement of personnel is one of the key aims of the new Directive but detailed requirements for education and training are the competence of the Member States. However, some level of harmonisation is considered essential by users and stakeholders if a level playing field allowing free movement of personnel is to be achieved. The majority of Member States have established a formal authorisation process for personnel, with defined education, training and competence requirements. In some the responsibility for ensuring appropriate education and training lies with the establishment. The majority view from the users (63%) was that ensuring and maintaining competence of staff was being satisfactorily addressed, but differences in expectations of training requirements between Member States have been reported, such that duplication of training is still required in some cases. There is currently little clarity on the expectations for continued professional development (CPD). The agreed EU Education and Training Framework has been published to promote harmonisation through acceptance of training according to a common modular framework and specified learning outcomes. Despite this, there are obviously still concerns over recognition of training delivered elsewhere. This was highlighted at the public consultation meeting, where comments were received that scientists were still having to repeat training when moving between Member States and that much work was still needed to facilitate free movement. A few difficulties are also being encountered in relation to access to training, including availability of training courses, in particular for the less common species. Training was also suggested for specific functions such as members of AWB as well as further guidance on assessment of competence. There is an important role for the Education and Training Platform in Laboratory Animal Science (ETPLAS) in increasing awareness of availability and quality of training courses by engaging with all relevant stakeholders to progress with commonly acceptable quality standards. ETPLAS was formed as a result of the recommendation contained in the EU Education and Training Framework assembling the three key players and facilitators, namely the relevant Member State authorities, course providers and course accreditors. The activities of the platform are still evolving, but progress has been limited due to lack of resources and active engagement by all three parties. Recommendations ØEfforts should be made by all relevant stakeholders to improve availability and access to, and variety of, training courses essential for obtaining the requisite competences in different knowledge areas, techniques and species. ØThe three partners of ETPLAS (Member State representatives, course providers and accreditors) should increase collaboration and engagement in order to progress with the development and agreement of common quality standards aimed at free movement of competent staff. ØETPLAS should take a more active role and step up its efforts to establish itself as a central repository for information on LAS (Laboratory Animal Science) training and quality standards in EU. 1.4 Harmonisation of welfare standards and stricter animal welfare measures (Annexes III and IV, Article 2)

Annex III defines standards for care and accommodation of animals which are now fully mandated in all Member States since the beginning of 2017. Annex IV defines appropriate methods of killing. Article 2 created the possibility in certain circumstances for Member States to maintain more stringent animal welfare standards in force before the new Directive was adopted. This affected mainly the retention of standards of accommodation and care higher than those contained in Annex III, which was intended to set common standards across EU, and form part of the framework for creating a level playing field. So, from the outset, there were always going to be some minor differences among Member States. Whilst similar standards were already in place in some countries previously, Directive 2010/63/EU introduced for the first time clear, mandatory standards across all Member States, in some cases resulting in much improved welfare practices than contained in the previous guidance. Over half the user respondents of the consultation thought that the Directive had improved animal welfare by application of improved housing and care practices, including for example inclusion of enrichment requirements and the need for trained and competent care staff. For some, daily monitoring of animals, including at weekends and holidays has been introduced which was generally seen as highly beneficial. There is increased awareness of the need for careful consideration of animal welfare, with appropriate defined and legally enforceable standards. For many Member States, with implementation of Annex III, the enclosure sizes for certain species has changed, requiring significant investment in new or alterations to buildings and enclosures. Although this was raised as a significant issue in the Impact Assessment that accompanied the Commission proposal for the new Directive, few issues were raised in the responses concerning the investments needed, possibly as the welfare benefits were acknowledged and an additional four years had been given until January 2017 to meet these new standards. Concerns were raised that the size of certain of the bird enclosures was incompatible with good welfare in certain circumstances. These concerns should be considered as part of future adaptations of Annex III (see below). Annex IV contains a list of approved standard methods of killing, for which no specific project authorisation is necessary, although competence in the persons performing the task is obligatory. Concerns were expressed that some of the methods for certain species were now “proven” to be unsuitable and should be deleted. As well as Annex IV methods, Member States may authorise additional methods to be used without project authorisation if the competent authority is satisfied that there is sufficient evidence that the method is as humane as those in Annex IV for that species. Member States must provide an annual report to the European Commission on additional methods of killing approved in each calendar year under Article 6(4)(a). Annex IV is foreseen to be amended through delegated powers in due course (Article 50) to include such additional methods, and remove any which are deemed unsuitable. There were significant concerns expressed by animal protection stakeholders that Article 2 would prohibit uptake of improved practices. The Directive does not prevent the application of improved care practices as this is firmly embedded in the Directive requiring that the Three Rs are continuously applied (for example Articles 4, 13, 27). When it is intended to propose changes to Annex III standards, these should be based upon sound reproducible evidence. With the delegated powers embedded in the Directive, benefits of any such changes will be able to be accrued throughout EU and not impact only on animals in a single Member State, if such evidence-based cases can be made for changes to Annex III. Recommendations ØMember States should provide evidence-based cases to the Commission services where amendments to Annexes III and IV are considered appropriate. ØWith the proposal to include standards for, inter alia, cephalopods in Annexes III and IV, the European Commission should consider other amendments on the basis of exemptions granted under Article 6(4)(a) and other evidence brought forward. Section 2 – Animal Welfare and the Three Rs i Introduction The Directive has introduced a number of elements that should contribute to systematic application of the Three Rs, improved animal welfare, the uptake and use of existing alternatives approaches (in its largest sense covering replacement, reduction and refinement) and to further accelerate the development, validation and regulatory acceptance of new alternative approaches. Beyond the provisions establishing uniform welfare standards such as binding care and accommodation conditions or methods of killing, the systematic, case by case application of project evaluation is expected to deliver one of the most significant impacts in ensuring compliance with the Three Rs. This allied to the activities of the AWB and the requirements for training and competencies are expected to derive significant welfare improvements in animal care and use. This section will first discuss the findings on a series of provisions all aimed at improving welfare of animals and proper balancing of the Three Rs. The section will then evaluate the impacts of the project evaluation process on achieving its objectives, including how existing alternative approaches are taken up and integrated in the projects. Finally, some comments are incorporated on how the development, validation and regulatory acceptance of new alternative approaches are impacted by the provisions of this Directive. 2.1 Animal Welfare Bodies, AWB (Articles 26 and 27)

Articles 26 and 27 lay out the requirements for one of the important new aspects of the Directive, the AWB. It has a central role in ensuring continuous application of the Three Rs in all care and use of animals within the establishment. The requirement for AWB has been welcomed by Member States, users and stakeholder organisations. There are significant positive indicators of the benefits of the introduction of AWB, in particular the heightened awareness within establishments of welfare needs, in particular with regard to refinements. The size and complexity of AWB vary significantly, in some cases dependent on the nature and size of establishment, the previous requirements in place before the Directive, and on the specific Member State transposition of Articles 26 and 27. In a number of Member States, the Designated Veterinarian is included as a required member of AWB. This has been received positively. There were many examples in all scientific sectors and in many Member States, of positive benefits to both animal welfare, with refinement of procedures, and improved experimental design following discussion of projects within the AWB. The interactions in AWBs among scientists, care staff and veterinarian are viewed very positively. Where the AWBs are properly resourced, with staff having appropriate skills, (including in all the relevant species), and where the decisions made by it are supported by establishment management, they can deliver the requirements and aspirations of the Directive. This requires balanced representation from science and welfare interests. Significant advantages have been reported with inclusion of specific expertise on experimental design. External (sometimes lay) input is also often considered beneficial, especially in considering the non-technical project summaries as part of the support given by the AWB during the development of a project proposal. Specific skills on alternatives and literature searching are rarely included in the composition of AWB, but some have suggested that their inclusion would have significant benefit. In some Member States, the role of AWB is reported as unclear, in particular where preliminary evaluation of projects is performed within the establishment. As the required tasks of AWBs and project evaluators are different (Articles 27 and 38 respectively), it is very important that each is aware of what they must do, and that the competencies of personnel involved are appropriate for these separate processes. AWBs have a number of different tasks within the establishment to support good animal welfare practices, and sufficient resource must be available to meet these, in particular where a considerable amount of time is taken up with project development. It is vital that all of the core tasks of the AWBs are performed and not constrained to assisting in the development of projects. However, where there is effective completion of all their designated tasks, this will positively contribute to the local culture and processes such that the time required for project development is likely to be reduced. Users reported that the AWB has had a positive impact in improving the culture of care, for example by increasing numbers and improving quality of staff, including by better training, by improving communications between them and improving teamwork directed towards optimising animal welfare and ensuring robust scientific output. Feedback from Member States on inspections supported the view that AWBs are developing well, and impacting positively on animal welfare within establishments. It is considered essential to ensure AWBs are properly resourced and decisions supported by management to effectively deliver the requirements of AWB. The composition of AWB is generally wider than set out in the Directive, often with the Designated Veterinarian as a full member, and including individuals with specific expertise on Three Rs and experimental design.. There needs to be a balanced representation from science and welfare interests. 2.1.1 AWB and impact on the Three Rs and animal welfare Stakeholder responses Animal Welfare Bodies have improved the implementation of the Three Rs and welfare of animals in my country/region. All stakeholders Other stakeholder organisations Animal protection organisations

The overall responses from stakeholder organisations were positive, but significant differences were again noted when the views from scientific and animal protection organisations were separated. Animal protection stakeholder comments General concerns were expressed over lack of visibility or clarity over roles of AWB, and therefore it was difficult to form a view on how these are working. The minimum composition as set out in the Directive is considered inadequate, and the Designated Veterinarian should be a legal requirement. However, AWB with appropriate training and support can contribute positively to animal welfare. ·"It is neither publicly known whether all relevant institutions have already established AWBs, nor how they are composed nor whether they fulfil their legal function." ·"The work (if any) of animal welfare bodies is hidden so there is no way to evaluate the outcome." ·"There are no obligations made on official training for the 3Rs and bio-statistics" Other stakeholder comments The responses acknowledged benefits of AWBs, but highlighted the need to ensure appropriate composition, expertise and resourcin