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
Date: 2017-11-08
Institutions: Directorate-General for Environment, European Commission
Subjects: animal experimentation, animal welfare, bio-ethics, protection of animals, scientific research, veterinary inspection

EN 

  EN 

   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}  
 
 
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 

 
 
 
 
 
 
CONTENTS 

Executive Summary ................................................................................................................................. 4 

i. Introduction ......................................................................................................................................... 5 

i.i Purpose and structure of the Report .............................................................................................. 6 

i.ii Timing of the Review ...................................................................................................................... 6 

ii. Consultation strategy and backgound information ............................................................................ 7 

Ii.i Stakeholder input ........................................................................................................................... 7 

ii.ii Other information sources ............................................................................................................ 8 

iii. Analysis of the responses to the consultations .................................................................................. 8 

iii.i Limitations and interpretation of the results ................................................................................ 8 

iii.ii Background of the respondents ................................................................................................... 9 

iv. General views ................................................................................................................................... 11 

iv.i General impact of the Directive on standards of animal welfare, care and use of animals ....... 12 

iv.ii Effect of the Directive on the quality of science ........................................................................ 14 

iv.iii Continuation of high-quality research in the EU using animals, where still necessary ............. 17 

Section 1 - Harmonisation of legislation ............................................................................................... 21 

i Introduction .................................................................................................................................... 21 

ii General views on harmonisation objective .................................................................................... 23 

1.1 Project Evaluation and Authorisation (Articles 36-42, 44) ......................................................... 26 

1.1.1 Project evaluation (Article 36 and 38) ................................................................................. 27 

1.1.2 Multiple generic projects (Article 40) .................................................................................. 33 

1.1.3 Simplified administrative procedure (Article 42) ................................................................. 34 

1.1.4 Authorisation decisions (Article 41) ..................................................................................... 35 

1.1.5 Role of National Committees (Article 49) ............................................................................ 37 

Recommendations ........................................................................................................................ 38 

1.2 Changes in Scope of Directive (Articles 1 and 5) ......................................................................... 38 

1.2.1 Inclusion of cephalopods (Article 1) .................................................................................... 39 

1.2.2 Foetal forms of mammals in the last third of normal development (Article 1) ................... 39 

1.2.3 Animals used for the purposes of education and training (Article 5) .................................. 41 

1.2.4 Animals used for the purposes of routine production (Article 5) ........................................ 43 

Recommendations ........................................................................................................................ 44 

1.3 Education and training of staff (Article 23) ................................................................................. 44 

Recommendations ........................................................................................................................ 45 

1 

 
 
 
1.4 Harmonisation of welfare standards and stricter animal welfare measures (Annexes III and IV, 
Article 2) ............................................................................................................................................ 46 

Recommendations ........................................................................................................................ 47 

Section 2 – Animal Welfare and the Three Rs ...................................................................................... 47 

i Introduction .................................................................................................................................... 47 

2.1 Animal Welfare Bodies, AWB (Articles 26 and 27) ..................................................................... 48 

2.1.1 AWB and impact on the Three Rs and animal welfare ........................................................ 49 

2.1.2 AWB and impact on the quality of science .......................................................................... 53 

2.1.3 Obstacles in delivering tasks of the AWB ............................................................................ 55 

2.1.4 Guidance on AWB ................................................................................................................ 56 

Recommendations ........................................................................................................................ 56 

2.2 National Committees (Article 49) ............................................................................................... 57 

Recommendations ........................................................................................................................ 60 

2.3 Training and education and requirements for personnel (Articles 23 and 24) .......................... 60 

2.3.1 Education, training and competence requirements on staff ............................................... 60 

2.3.2 Other named, responsible persons in Articles 24 and 27 .................................................... 63 

Recommendations ........................................................................................................................ 66 

2.4 Reuse (Article 16) ........................................................................................................................ 66 

Recommendations ........................................................................................................................ 67 

2.5 Avoidance of unnecessary duplication (Article 46 and Annex VI) .............................................. 67 

Recommendations ........................................................................................................................ 69 

2.6 Setting free and rehoming (Article 19) ....................................................................................... 70 

Recommendations ........................................................................................................................ 71 

2.7 Sharing organs and tissues (Article 18) ....................................................................................... 71 

2.8 Use of existing alternative approaches and implementation of the Three Rs ........................... 74 

2.8.1 The role of project evaluation on the use of alternative approaches and implementation of 
the Three Rs .................................................................................................................................. 74 

2.8.2 Use of existing alternative approaches ................................................................................ 80 

Recommendations ........................................................................................................................ 88 

2.9 Development, validation and regulatory acceptance of new alternative approaches............... 89 

Recommendations ........................................................................................................................ 93 

Section 3 – Improving transparency ..................................................................................................... 93 

3.1 Non-Technical Project Summaries (Article 43) ........................................................................... 96 

Recommendations ........................................................................................................................ 98 

2 

 
 
 
3.2 Statistical data (Article 54) .......................................................................................................... 98 

Recommendations ........................................................................................................................ 99 

3.3 Project Evaluation (Articles 36 and 38) ....................................................................................... 99 

Recommendations ...................................................................................................................... 100 

3.4 Inspections (Article 34) ............................................................................................................. 101 

Section 4 - Additional comments ........................................................................................................ 101 

List of abbreviations ............................................................................................................................ 104 

Annexes ............................................................................................................................................... 106 

Annex 1: List of recommendations ................................................................................................. 107 

Annex 2: Report by EURL ECVAM ................................................................................................... 112 

3 

 
 
 
 
 
 
This Staff Working Document is in support of the Article 58 Review Report1, 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 
increasing 
transparency. 

link  between animal welfare  and  good  science,  and 

the 

1 [OJ reference to be added once adopted] 

4 

 
 
 
                                                            
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. 

5 

 
 
 
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. 

6 

 
 
 
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  questionnaires2  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.  

2 http://ec.europa.eu/environment/chemicals/lab_animals/related_topics_en.htm 

7 

 
 
 
                                                            
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”3.  

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  Communication4  in  response  to  European  Citizens'  Initiative  "Stop 
Vivisection"  and  the  outcome  of  a  subsequent  Commission  Scientific  Conference 
"Non-animal approaches – the way forward"5.  

3 http://ec.europa.eu/environment/chemicals/lab_animals/pdf/Scheer_may2017.pdf 
4 C(2015) 3773 final, http://ec.europa.eu/environment/chemicals/lab_animals/pdf/vivisection/en.pdf  
5 http://ec.europa.eu/environment/chemicals/lab_animals/3r/pdf/scientific_conference/non_animal_approaches 
_conference_report.pdf  

8 

 
 
 
                                                            
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 

FR 

Number 
respondents 
306 

% of total 
respondents 
34.42% 

No 
AWB* 
600 

% AWB 
responding 

51.00% 

9 

 
 
 
IT 
DE 
SK 
UK 
multi** 
SE 
BE 
NL 
AT 
ES 
PT 
HU 
RO 
DK 
CZ 
PL 
IE 
EL 
FI 
HR 
EE 
LT 
SI 
LV 
LU 
BG 
CY 
MT 

106 
82 
47 
47 
37 
33 
31 
26 
21 
21 
20 
18 
17 
15 
14 
14 
9 
8 
7 
6 
5 
3 
3 
2 
1 
0 
0 
0 

11.92% 
9.22% 
5.29% 
5.29% 
4.16% 
3.71% 
3.49% 
2.92% 
2.36% 
2.36% 
2.25% 
2.02% 
1.91% 
1.69% 
1.57% 
1.57% 
1.01% 
0.90% 
0.79% 
0.67% 
0.56% 
0.34% 
0.34% 
0.22% 
0.11% 
0.00% 
0.00% 
0.00% 

145 
275 
23 
170 
0 
40 
300 
70 
40 
244 
20 
35 
40 
45 
85 
220 
21 
45 
25 
20 
3 
4 
11 
5 
7 
13 
1 
3 

73.10% 
29.82% 
204.35% 
27.65% 

82.50% 
10.33% 
37.14% 
52.50% 
8.61% 
100.00% 
51.43% 
42.50% 
33.33% 
16.47% 
6.36% 
42.86% 
17.78% 
28.00% 
30.00% 
166.67% 
75.00% 
27.27% 
40.00% 
14.29% 
0.00% 
0.00% 
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)6. For France, 107 (35%) were SMEs. 

6 C(2003) 1422, Commission Recommendation concerning the definition of micro, small and medium-sized 
enterprises,  OJ L 124, 20.5.2003, p. 36–41 

10 

 
 
 
  
                                                            
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) 

Contract Research Organisation 

Food- and feed sector 

Other 

Pharmaceutical industry (including 
both human and animal health) 

Not specified 

Total 

Types of species used 

8 

1% 

38 

11 

13 

4% 

1% 

1% 

120 

13% 

699 

889 

79% 

100% 

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  

11 

 
 
 
 
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. 

12 

 
 
 
 
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. 

13 

 
 
 
 
 
 
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:  

14 

 
 
 
 
 
 
 
“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 

15 

 
 
 
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 
 
  Further improvement in animal welfare and Three Rs leading to better science 

Improved quality of monitoring of animals 

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." 

16 

 
 
 
 
       
 
 
 
 
 
  "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 

17 

 
 
 
 
 
 
 
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." 

18 

 
 
 
  "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 

19 

 
 
 
 
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 

20 

 
 
 
 
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. 

21 

 
 
 
 
 
"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 

22 

 
 
 
 
 
 
 
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 

23 

 
 
 
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 

24 

 
 
 
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. 
between 
evaluators/evaluations  within  the  same  Member  State,  and  over  inconsistencies  between 
Member States on authorisations issued. 

inconsistencies 

concerns 

raised 

Some 

users 

over 

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 

25 

 
 
 
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." 

26 

 
 
 
 
  "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.   

27 

 
 
 
 
 
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. 

28 

 
 
 
 
 
 
 
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. 

29 

 
 
 
 
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 

implementation  at 
country\regional  level.  One  of  the  key  areas  of  concern  for  private and  public 
research lies in slowness of the authorisation process." 

in  harmonisation 

/ 

  "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.  

30 

 
 
 
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 processes7.  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 
  and  project  authorisation,  including,  in  particular,  impartiality, 
project  evaluation 
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.  

7 http://ec.europa.eu/environment/chemicals/lab_animals/pdf/Endorsed_PE-RA.pdf 

31 

 
 
 
                                                            
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. AFSTAL8/LASA9 to FELASA10). 

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. 

8 https://www.afstal.com/ 
9 http://www.lasa.co.uk/ 
10 http://www.felasa.eu/ 

32 

 
 
 
                                                            
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  
No 
Not applicable 

18/28 
6/28 
4/28 

33 

 
 
 
 
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  
Yes 

17/28 
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. 

34 

 
 
 
 
 
 
 
 
 
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 
No 

25/28 
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 
Too early 
No opinion 
No response submitted 

16/28 
 6/28 
 1/28 
 5/28 

35 

 
 
 
 
 
 
 
 
 
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  
Yes 

22/28 
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? 

No   
Yes 
Total responses 

All users 

France 

No 
273 
616 
889 

% 
31% 
69% 
100% 

No 
144 
162 
306 

% 
47% 
53% 
100% 

Rest of EU 
% 
22% 
78% 
100% 

No 
129 
454 
583 

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? 

36 

 
 
 
 
 
 
 
  
  
 
 
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  
Yes 

 8/28 
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 

37 

 
 
 
 
 
 
 
 
 
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 
No 

 14/28 
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 

38 

 
 
 
 
 
 
 
 
 
 
 
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.  

39 

 
 
 
 
 
 
 
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. 

No 
Yes 
Total responses 

All users 

France 

No 
327 
364 
691 

% 
47% 
53% 
100% 

No 
190 
68 
258 

% 
74% 
26% 
100% 

Rest of EU 
% 
No 
32% 
137 
68% 
296 
100% 
433 

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." 

40 

 
 
 
 
 
 
 
  
  
 
  "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 

41 

 
 
 
No 
No opinion / NA 
Too early to assess 

 3/28 
8/28 
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  

  The  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". 

42 

 
 
 
 
 
  Member 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.    

  Where 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. 

  Member  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. 

  Training  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. 

  Urgent  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.  

43 

 
 
 
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 
No 
No view/NA 
Too early to assess 

Impact on quality of science 
Yes 
No 
No view/NA 
Too early to assess 

8/28 
10/28 
4/28 
6/28 

5/28 
6/28 
7/28 
10/28 

44 

 
 
 
 
 
 
 
 
Impact on animal welfare 
Yes 
No 
No view/NA 
Too early to assess 

8/28 
5/28 
6/28 
9/28 

User responses 

Is your organisation using foetal forms of mammalian species? 

No 
Yes 
Total responses 

No 
641 
248 
889 

% 
72% 
28% 
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 
Yes 
Too early 
No view/NA 
Total responses 

Impact on quality of science 
No 
Yes 
Too early 
No view/NA 
Total responses 

Impact on animal welfare 
No 
Yes 
Too early 
No view/NA 
Total responses 

No 
88 
117 
26 
17 
248 

No 
153 
37 
43 
15 
248 

No 
134 
63 
35 
16 
248 

% 
35% 
47% 
10% 
7% 
100% 

% 
62% 
15% 
17% 
6% 
100% 

% 
54% 
25% 
14% 
6% 
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. 

45 

 
 
 
 
  
 
 
 
 
 
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 
No 
No view/NA 
Too early to assess 

8/28 
13/28 
4/28 
3/28 

Impact on quality of teaching 
Yes 
No 
No view/NA 
Too early to assess 

6/28 
14/28 
4/28 
4/28 

Impact on animal welfare 
Yes 
No 
No view/NA 
Too early to assess 

10/28 
12/28 
4/28 
2/28 

User responses  

Is your organisation using animals for the purposes of education and training? 

46 

 
 
 
 
 
 
 
No 
Yes 

No 
496 
393 

% 
56% 
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 
Yes 
Too early 
No opinion/NA 
Total responses 

Impact on quality of teaching 
No 
Yes 
Too early 
No opinion/NA 
Total responses 

Impact on animal welfare 
No 
Yes 
Too early 
No opinion/NA 
Total responses 

No 
133 
202 
31 
27 
393 

No 
166 
178 
28 
21 
393 

No 
188 
161 
29 
15 
393 

% 
34% 
51% 
8% 
7% 
100% 

% 
42% 
45% 
7% 
5% 
100% 

% 
48% 
41% 
7% 
4% 
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 

47 

 
 
 
  
 
 
 
 
 
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.” 

48 

 
 
 
 
 
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 
Yes 
Total responses 

No 
792 
97 
889 

% 
89% 
11% 
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 
Yes 
Too early 
No opinion/NA 
Total responses 

Impact on quality of science 

% 
43% 
41% 
5% 
10% 
100% 

% 

No 
42 
40 
5 
10 
97 

No 

49 

 
 
 
 
  
 
 
 
No 
Yes 
Too early 
No opinion/NA 
Total responses 

Impact on animal welfare 
No 
Yes 
Too early 
No opinion/NA 
Total responses 

56 
27 
6 
8 
97 

No 
51 
35 
5 
6 
97 

58% 
28% 
6% 
8% 
100% 

% 
53% 
36% 
5% 
6% 
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  

  Further guidance should be developed to improve clarity on the minimum threshold of 

severity needed to bring a procedure under the scope of the Directive. 

  The  European  Commission  should  propose  amendments  to  Annexes  III  and  IV  for 

cephalopods once sufficient evidence is available. 

  The 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, 

50 

 
 
 
 
 
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  Framework11  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  

  Efforts 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. 

  The  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. 

11 http://ec.europa.eu/environment/chemicals/lab_animals/pdf/guidance/education_training/en.pdf 

51 

 
 
 
                                                            
  ETPLAS 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. 

52 

 
 
 
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  

  Member  States  should  provide  evidence-based  cases  to  the  Commission  services 

where amendments to Annexes III and IV are considered appropriate. 

  With 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. 

53 

 
 
 
 
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. 

54 

 
 
 
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 

55 

 
 
 
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 

56 

 
 
 
 
 
 
 
The  responses  acknowledged  benefits  of  AWBs,  but  highlighted  the  need  to  ensure 
appropriate  composition,  expertise  and  resourcing.  AWBs  need  to  be  empowered  by  the 
establishment management. 

  "Beyond  compliance  with  processes,  welfare  is  put  at  the  centre  of  operations  and 

welfare considerations are brought to the daily operational level." 

  "The mere existence of AWBs is an indication of progress, as formerly they were a lot 

less widespread from a European-wide perspective" 

  "In countries where AWB were already established, improvements will vary, but they 
have  had  a  positive  impact.  They  have  proved  useful  for:  1)  Disseminating  best 
practice  and  addressing  concerns  2)  Improving  cross  stakeholder  dialogue  between 
scientists,  veterinary  staff,  animal  welfare  staff  3)  The  monitoring  of  compliance  in 
the establishment" 

  "It  is  unquestionable  that  the  AWBs  have  increased  the  awareness  of  scientists  to 
focus  more  on  animal  welfare.  Beyond  compliance,  welfare  considerations  are 
brought directly to the “ground”/everyday operations" 

  "Where  it  has  been  reported  that  AWB  members  are  non-scientists  they  have 

sometimes failed to advise researchers correctly negatively affecting research." 

57 

 
 
 
 
 
 
User responses 

Have  the  Animal  Welfare  Bodies  contributed,  through  tasks  defined  in  Article  27,  to  an 
improved welfare of animals in general and facilitated the uptake of the Three Rs within your 
establishment (whether breeder, supplier or user)? 

The  majority  of  users  were  of  the  view  that  AWB  had  contributed  to  improved  welfare  in 
their establishment. Many of those answering negatively indicated that a similar framework 
had been in place prior to the new Directive. 

A  number  of  specific  examples  of  where  AWB  had  contributed  to  improved  welfare  or 
uptake of the Three Rs were submitted. These include 

 

Improved  housing  including  provision  of  nesting  materials;  refinement  of  animal 
housing,  especially  with  less  well-known  species;  provision  of  “group”  advice  on 
renovations; specific health status monitoring. 

  Training and habituation of  animals to procedures; improved handling; development 
of a socialisation plan including specific exercise regimens; improvement of breeding 
programmes. 

  Adaptation in sampling including micro-sampling; improved surgical techniques and 
peri-operative care; refined endpoints; use of “alert” cards on cages to require action; 
additional  monitoring;  better  record  keeping;  establishing  post-operative  follow-up 
score sheets; improved methods of anaesthesia and euthanasia.  

 

 

Improved  training  in  aspects  of  care  and  recognition  of  pain  and  distress  including 
enforcing daily observation of animals; improved supervision of junior scientists. 

Improved  communication  between  care  and  scientific  staff;  valued  input  by 
Designated Veterinarian – in some cases a mandated member of the AWB. 

  "Fewer animals used due to statistical review or exchange of ideas about how more 

can be obtained from fewer animals." 

  "There  is  “more  exchange  of  best  practices.  Problems  are  identified,  discussed  and 

solutions are proposed.” 

58 

 
 
 
 
 
  "Follow  up  on  work  done  has  encouraged  (further)  improvements  especially  when 
unexpected events happen (with welfare consequences) when AWB reviews complete 
report to try to learn lessons for the future." 

  “AWB members are also split in sub groups to address specific areas e.g. the 3Rs / 
animal  care  and  accommodation,  harm  /  benefit  analysis,  management  systems, 
training. Champions of the function groups lead in addressing specific areas,  - This 
approach  allows  in  depth  reviews  of  each  area  and  implementation  of  actions 
identified.” 

  “recognises  local  good  practice  through  awards,  sponsors  3Rs  lectures,  poster 

events” 

  “Quarterly  newsletter  now  produced;  1:1  discussions  held  with  project  licence 

holders about 3Rs” 

  “Alternative species seminars” 

Of those who said it was not beneficial, for many this was because a similar process was 
already in place and in some cases the respondents said that the person in charge of the 
unit was already doing those tasks. For a few they saw it as additional bureaucracy / cost 
without benefit. Many of these places seem to be small, and with a small number of well-
defined programmes, for example provision of blood products. 

the  Animal  Welfare  Bodies  been  effective 

Have 
communication between different members of staff (e.g. scientific/technical/veterinary)? 

improving  participation  and 

in 

No 
Yes 
Too early 
No opinion/NA 
Total responses 

All users 

France 

No 
118 
610 
76 
85 
889 

% 
13% 
69% 
9% 
10% 
100% 

No 
38 
223 
27 
18 
306 

% 
12% 
73% 
9% 
6% 
100% 

Rest of EU 
% 
14% 
66% 
8% 
11% 
100% 

No 
80 
387 
67 
49 
583 

On  the  specific  question  concerning  the  impact of  AWB  on  improving  communication,  the 
French users seemed to hold a slightly more positive view. However, some of those who said 
that no impact had been noted, often commented on similar structures having been in place 
already previously. 

On positive impact on communication, users stated: 

  "Encourages “peer to peer" discussion and communication” 

  “more consideration and respect, from the users, for the lab animals used” 

59 

 
 
 
 
  
  
 
  “Animal  Welfare  Body  in  our  institution  has  enabled  more  communication  (formal 
and  informal)  between  different  participants  in  animal  experiments  and  animal 
welfare  which  enables  better  awareness  about  various  issues  in  connection  with 
animals in experiments” 

60 

 
 
 
 
 
2.1.2 AWB and impact on the quality of science 

Member State responses 

Have  Animal  Welfare  Bodies  been  effective  in  improving  the  quality  of  science  within 
establishments? 

Yes 
No 
No opinion 
Too early to assess 

12/28 
 1/28 
 3/28 
12/28 

There are indications in the Member State responses  that AWB are impacting positively on 
the  quality  of  animal  research  being  conducted  within  establishments. It  was  noted  that  the 
structure promotes improved and positive interactions and exchanges of information among 
the animal care and scientific staff.  Input from the Designated Veterinarian was considered 
very helpful. 

A number of responses noted the improved quality of project applications following input by 
AWB,  in  particular  in  refinements  and  animal  care,  contributing  to  improved  science.  This 
helped the efficiency of the project evaluation process. 

User responses 

Have  the  Animal  Welfare  Bodies  been  effective  in  improving  the  quality  of  science  (e.g. 
through  contributing  into  project  proposals  and  monitoring  of  their  outcomes)  within  your 
establishment? 

There  were  some  differences  in  views  among  French  users  compared  to  the  rest  of  the  EU 
with the latter seeing the benefits to science more positively, from 24% to 39%. 

Yes 
No 

All users 

France 

No 
271 
200 

% 
33% 
25% 

No 
70 
77 

% 
24% 
26% 

Rest of EU 
% 
39% 
24% 

No 
201 
123 

61 

 
 
 
 
 
 
  
  
Too early 
No opinion/NA 
Total responses 

224 
119 
814 

28% 
15% 
100% 

100 
50 
297 

34% 
17% 
100% 

124 
69 
517 

24% 
13% 
100% 

Of those who thought the AWB had contributed to the scientific quality, the cited examples 
included:  

 

Improved  project  applications  following  AWB  check;  improved  literature  review 
reducing  duplication  of  experiments;  scientific  contribution  from  members  of  the 
AWB (peer review) that improves the quality of project proposals; better definition of 
projects,  avoiding  unplanned,  non-standardised  experiments;  determining  whether 
hypothesis  will  truly  be  answered  by  study  design,  with  the  expectation  of  clear 
experimental results. 

  Optimising  experimental  design;  statistics,  randomising  and  blinding;  improving 
replication  and  improving  reproducibility;  model  homogeneity  including  defined 
standard procedures, with no interference of pain or animal stress. 

  Stopping  experiments  when  confounding  factors  influence  science;  reduce  the 
severity  of  models  to  better  evaluate  the  activity  of  drug  candidates;  avoid  using 
animals that are injured; avoid interactions between animal health status/welfare and 
the  readouts  of  the  studies;  better  record  keeping  and  standardised  methodologies 
within establishment. 

 

Internal sharing of tissues. 

  "developed a special cage for irradiation, which secures the correct irradiation dose 
for  the  animals,  thereby  increasing  animal  welfare  and  improving  experimental 
results" 

Of those who responded that the AWB had not affected quality of science, some stated that 
they  do  not  consider  scientific  quality,  some  leaving  this  to  the  project  evaluation  by  the 
competent  authority,  and  others  to  experts  not  included  in  AWB.  Some  believe  that  the 
personnel  on  the  AWB  do  not  have  the  necessary  scientific  skills  especially  in  particular 
areas. Some felt that this should not be a role for the AWB, but others in the establishment. 

Examples of potential detriment to science: 

  "Scientific  requirement,  e.g.  individual  animal  housing  when  appropriate,  is  being 
over-ruled  even  where  animals  are  provided  with  significant  interaction  time  and 
playtime.  This results in certain types of projects being unworkable (topical efficacy) 
due to individual, subjective and personal considerations. Directive and its guidance 
should be encouraging good science and welfare within EU rather than try to force 
scientific use of animals, to areas outside EU." 

62 

 
 
 
 
 
 
2.1.3 Obstacles in delivering tasks of the AWB 

User responses 

Have  obstacles  been  encountered  in  delivering  the  tasks  of  the  Animal  Welfare  Body  in 
Article 27? 

More  than  half  of  the  user  responses  responded  that  no  difficulties  had  been  encountered 
when delivering the tasks of the AWB. 

Training,  resources  and  having  sufficient  authority  were  the  main  issues  of  concern  raised. 
AWB members need to be trained for their specific tasks, including effective knowledge of 
the species involved and understanding of the requirements of the scientific research. Skills 
on experimental design were considered very helpful. 

Expertise in alternative methods is reported as less than ideal in some establishments.  

Feedback on obstacles included 

  Duplication  of  work  between  project  evaluation  and  AWB  (and  user  committees  or 

other parts of institution) was reported by some. 

  Lack  of  clarity  on  expectations  of  content  of  applications  for  project  evaluation  
makes it difficult for AWB to contribute effectively and efficiently to support project 
applicants. 

 

Inadequate resourcing. 

  No  guidance  on  addressing  conflicts  of  interest  (including  some  with  independence 

from the institution).  

 

 “There are a lot of established scientists in the animal welfare body, thinking "we are 
doing a good job for decades". For animal caretakers it is hard to be heard.”  

  "Domination by a single person, or poor chairperson, not in the interests of optimal 

functioning and balanced outcomes taking views of all." 

63 

 
 
 
 
 
2.1.4 Guidance on AWB 

EU  Guidance  on  the  composition  and  functioning  of  the  AWB  has  been  agreed  and 
disseminated12.  In  response  to  the  question  on  the  need  for  further  guidance,  many  of  the 
suggestions would seem to be already addressed in the existing EU guidance.  

User responses 

Elements that were highlighted include 

 

Improve  status  of  and  ensure  appropriate  support  and  empowerment  for  the  AWB 
within an establishment. 

  Need for the development of training for members and opportunities to meet members 

from different establishments.  

 

Improve role of National Committee (and National Contact Points) in communication 
and dissemination of best practices. 

  Better  dissemination  of  present  guidance  and  increase  awareness  of  other  relevant 

publications. 

Has the developed EU guidance on Animal Welfare Bodies been helpful? 

No 
Yes 
Too early 
Not aware 
No opinion 
Total responses 

All users 

France 

No 
107 
380 
106 
119 
119 
831 

% 
13% 
46% 
13% 
14% 
14% 
100% 

No 
44 
108 
37 
63 
54 
306 

% 
14% 
35% 
12% 
21% 
18% 
100% 

Rest of EU 
% 
12% 
52% 
13% 
11% 
12% 
100% 

No 
63 
272 
69 
56 
65 
525 

Difference between French and other users seems to be due awareness of the guidance and 
availability of translated versions. 

Recommendations  

  Establishments  and  Member  States  (through  inspection)  should  ensure  that  all  core 

tasks of the AWB are being fulfilled. 

  Member  States  should  clarify  roles  and  responsibilities  of  the  AWB  and  project 
evaluation,  in  particular  where  there  may  be  some  integration  or  overlap  with 
following  the  development  of  projects,  including  application  of  the  Three  Rs  and 
project evaluation process. 

12 http://ec.europa.eu/environment/chemicals/lab_animals/pdf/guidance/animal_welfare_bodies/en.pdf 

64 

 
 
 
  
  
 
                                                            
  Senior  management  of  the  establishment  should  ensure that  the  AWB  has  sufficient 

resources and empowerment to carry out the required tasks. 

  Establishments  could  consider  the  addition  of  a  Designated  Veterinarian  as  a  full 

member of the AWB. 

2.2 NATIONAL COMMITTEES (ARTICLE 49) 

Article  49  of  the  Directive  describes  the  requirements  for  the  establishment  of  National 
Committees for the protection of animals used for scientific purposes in each Member State. 
National Committees should facilitate a coherent approach to project evaluation and promote 
the Three Rs as well as playing an important role in the exchange of good practice within the 
Member State and at the level of the Union. 

Although  a few Member States had similar Committees to those required under  Article  49, 
the  majority  of  Member  States  needed  to  set  these  up  from  scratch,  and  currently  many 
National  Committees  are  still  establishing  their  role  and  have  yet  to  make  an  impact  at 
national level. A few Member States have yet to establish their National Committee, and only 
18/28 were active at the time of the review.  

Many  users,  in  selected  Member  States,  were  unaware  of  the  existence  or  functions  of  a 
National Committee. 

However,  there  are  National  Committees  already  flourishing  with  the  development  of 
guidance material and development of networks with and sharing practices among AWB.   

There  has  been  one  meeting,  hosted  by  the  Commission,  of  National  Committee  chairs  to 
initiate communications and consider ways sharing of best practices, but at the time only 17 
National  Committee  representatives  were  able  to  attend,  and  effective  channels  of 
communication and information dissemination have yet to evolve.  

The  structure,  membership,  responsibilities  and  activities  of  National  Committees  vary 
significantly  among  Member  States,  and  concerns  were  raised  over  the  resources  made 
available to perform their functions. 

Member States and users were invited to consider the impact of the introduction of National 
Committee in promoting a consistent approach to project evaluation (covered under Section 1 
of this report), and on their effectiveness in supporting AWB. 

Member State responses 

Has  the  National  Committee  carried  out  activities  to  share/disseminate  best  practice  on 
animal welfare and use, and to advise Competent Authorities? 

No 
Yes 

 10/28 
 18/28 

65 

 
 
 
 
The  distribution  of  responses  again  reflects  the  relative  experience  of  the  National 
Committees. 

Advice has been offered to competent authorities and AWB on a range of topics including, 
for example, training, annual seminars for AWB members, web-sites with information on and 
links  to  Three  Rs  resources,  breeding  and  managing  of  surplus  genetically  altered  animals, 
recognition,  prevention  and  management  of  pain  and  on  approval  of  statutory  training 
programmes. 

Are there areas of difficulty being experienced? How can these be improved? 

One  suggestion  was  made  that  advice  developed  by  National  Committees  in  different 
Member States should be endorsed at EU level to strengthen its role.  

However, more experience is required with the new structures before informed views can be 
drawn. 

User responses 

Has the National Committee (Article 49) been effective in reaching out to the Animal Welfare 
Bodies  in  your  establishment  to  facilitate  their  role  and  provide  advice  on  matters  dealing 
with the acquisition, breeding, accommodation, care and use of animals, and ensure sharing 
of best practice? 

Although  many  are  still  in  the  early  stages  of  development,  progress  is  being  made  on 
communication  with  AWB,  for  example  a  web-based  platform  to  share  material  and 
information, and training/information days have been held in a number of Member States. 

It is important that all National Committee members are knowledgeable of their role, and as 
necessary, receive appropriate training.   

AWB  Regional  Hubs  developed  through  National  Committee  in  UK  was  mentioned  as 
positive, as it facilitates information exchange and identification of good practice. 

Improved  sharing  of  information  and  best  practice  is  requested,  however,  many  National 
Committees  are  still  evolving.  Suggestions  were  made  for  a  central,  easily  accessible 
repository for this purpose. 

66 

 
 
 
 
 
 
Stakeholder responses 

National Committees have helped establishments to improve the implementation of the Three 
Rs and animal welfare in my country/region. 

All stakeholders 

Other stakeholder organisations 

Animal protection organisations 

There  was  general  agreement  among  the  stakeholder  organisations  that  at  present  it  is  too 
early  to  form  a  view  on  the  impact  of  the  National  Committees.  Animal  protection 
organisations  were  concerned  over  the  lack  of  transparency  on  the  role,  function  and 
activities  of  National  Committees.  Lack  of  involvement  of  animal  protection  organisations 
was a common concern. 

  "Eurogroup surveyed the 28 MS in 2015. While some NCs are active and having an 
effect,  many  are  not  yet  fulfilling  their  required  functions,  and  others  have  not  yet 
even been formed. Some NCs lack the expertise required, and there is often little link 
or liaison with AWBs and a lack of transparency or involvement of stakeholders." 

  "As a national organization it is hard to answer that question because we don't know 

it." 

  "Efficient  National  Committees  are  rarely  seen.  In  most  cases,  countries  nominate 

them just "on the paper" but have little or no activity." 

67 

 
 
 
 
 
 
 
  "Not all countries have had the opportunity to build up their experience yet - this may 
still take a few years but in the meantime a systemic dialogue between the NCs may 
help  to  create  common  understanding  common  practice  which  should  help  overall 
implementation and harmonisation " 

  "In  several  countries  clarity  of  roles  and  responsibilities  of  national  committees  is 

still to be achieved." 

Recommendations  

  Member States should facilitate and resource National Committees where this is not 
yet established, or where it is not fully functional, to ensure that its role and tasks are 
fulfilled as these tasks play key roles in the attainment of the overall objectives of the 
Directive. 

  In  preparation  for  the  EU  implementation  report  under  Article  57,  Member  States 

should consider whether and how National Committees are:  

o  facilitating a coherent approach to project evaluation within the Member State 

and 

o  exchanging good practice, including the promotion of Three Rs.  

2.3  TRAINING  AND  EDUCATION  AND  REQUIREMENTS  FOR  PERSONNEL 
(ARTICLES 23 AND 24) 

2.3.1 Education, training and competence requirements on staff 

Animal  welfare  can  be  significantly  improved  when  staff  dealing  with  animals  are  well-
trained  and  competent.  In  its  Article  23,  the  Directive  requires  that  staff  carrying  out 
procedures on animals, caring  for, and killing animals are adequately  educated and trained, 
and provided with supervision until competence has been attained and demonstrated. 

The agreed EU Education and Training Framework13 promotes “learning outcome”-focused, 
modular-based  training  to  facilitate  tailor  made  provision  of  training  to  meet  the  specific 
needs and existing skill/knowledge set of the trainees. 

There was previously much variability in the training required before animal procedures were 
undertaken. Where formal high quality training was not previously implemented there were 
significant  benefits  reported  to  animal  welfare  and  design  of  experiments  following  the 
introduction  of  improved  measures  of  training  and  supervision.  Some  have  reported  that 
better training has led to better welfare, better recognition of pain and better understanding of 
animal behaviours and needs under different circumstances.  

Some AWBs have also contributed to this improvement. The requirement of the Directive for 
an establishment to  have a person responsible for training and competence (Article 24) has 

13 http://ec.europa.eu/environment/chemicals/lab_animals/pdf/guidance/education_training/en.pdf 

68 

 
 
 
                                                            
brought this issue to the fore. In some establishments, this person is a member of the AWB. 
Generally, the oversight of the person for training and competence was valued, but it seemed 
from some user responses that such a person had yet to have been appointed or to have had an 
overt,  visible  role.  Feedback  from  Member  States  on  inspections  indicated  that  common 
education and training practices and competence assessment are still under development, but 
the Article 24 training person was considered to be helpful. 

However,  many  organisations  with  a  specific  interest  in  alternatives  as  well  as  welfare 
organisations  stated  that  training  in  non-animal  alternatives,  and  in  searching  for  them  was 
not as good as it could be.  

Many  users  remain  unaware  of  the  EU  Guidance  and  other  guidance  documents  available 
from  the  Member  States,  or  the  respective  National  Committee.  There  is  clearly  room  for 
improved communication of these guidance documents. 

Member State responses 

The  Directive  requires  competence  in  those  persons  performing  a  number  of  functions 
(Article  23).  How  are  the  competence  requirements  ensured  in  the  Member  State 
(authorisation/other means)? 

Authorisation 
Other means 

 19/28 
9/28 

The  majority  of  Member  States  have  a  formal  authorisation  process  in  place,  with  defined 
educational requirements, in others the responsibility for ensuring appropriate education and 
training lies with the establishment. 

User responses 

Are there any difficulties in ensuring and maintaining competence in these staff? 

The  majority  view  from  the  users  (63%)  was  that  ensuring  and  maintaining  competence  of 
staff was being satisfactorily addressed. 

However, the difficulties encountered by others included 

69 

 
 
 
 
 
 
 
  Availability  (including  timeliness,  language)  of  species  specific  training  courses 
(amphibia,  farm  animals,  fish,  birds,  working  on  animals  in  the  wild),  including  in 
particular, the less commonly used species; cost of appropriate training. A catalogue 
of available training courses would be very helpful 

  Training  in  practical  methods  using  non-human  primates  is  prohibited  in  some 
Member States – N.B. this can be achieved when done under supervision and using 
procedures  required  as  part  of  another  authorised  scientific  project  (not  for 
educational or training purposes). 

  Training requirements in some Member States are not clear for users. 

long 

time;  no  clarification  of  ongoing 

  Difficulties in maintaining competences when people do not perform a procedure for 
training  (Continued  Professional 
a 
Development)  requirements;  ensuring  that  staff  working  outside  the  establishment 
(e.g.  work  in  the  wild)  maintain  and  demonstrate  competence;  fixed  frequency  of 
retraining is providing problems for some (implied that this has little/no benefit).  

  Maintaining sufficient competent staff.  

  Difficulties  in  ensuring  competence  in  killing  of  some  animals  e.g.  wild  animals 
which  are  not  killed  as  part  of  the  procedure;  assessing  competence  of  unusual  / 
complex procedures not done by others. 

  Separation  of  training  by  function  has  provided  difficulties  for  some;  in  one  case, 
formal  training  for  animal  care  staff  is  considered  to  be  less  organised  and  not 
guaranteed. 

  Training required for persons coming from outside the EU, and lack of recognition for 

'on the job' learning. 

  Difficulties in compelling researchers to change ways of thinking and practices which 

have been in use for many years 

  Time resource of trainers and person responsible for training and competence. 

  The position and the legal responsibilities of the person responsible for training and 

competence is reported to be not always as clear as it could be. 

Have any changes in attitudes toward animals been noted as a result of the increased focus 
on competence? 

70 

 
 
 
A marginal positive response to this question by users. 

Examples of good practice included: 

  “Establishing a culture of care within the organisation.” 

  “An ethos of continuous improvement has been started.” 

  “Better  training  has  led  to  better  welfare,  better  recognition  of  pain,  better 
understanding of animal behaviours and requirements under different circumstances” 

  “Working towards better definitions and application of endpoints.” 

2.3.2 Other named, responsible persons in Articles 24 and 27 

There has been a requirement for establishments to appoint other named persons, including a 
Designated Veterinarian (Article 27). Whilst this position was already established in several 
Member  States,  in  others,  users  reported  significant  improvements  due  to  the  formal 
appointment  of  this  role.  The  Designated  Veterinarian's  input  to  AWB  discussions  was 
considered valuable, and a number of Member States mandate the Designated Veterinarian as 
a permanent member of the AWB. The Designated Veterinarians had a significant impact in 
developing the training for and, assisting in the training of, other staff. 

little 

There seems to be some difficulty with the recognition and implementation of the role for the 
person  responsible  for  information  (Article  24(1)(b)),  in  particular  with  their  input  on 
scientific  considerations  of  animal  models  and  their  use.  This  role  was  rarely  mentioned 
suggesting 
information 
dissemination  of  many  types  (not  just  information  on  species)  was  considered  essential  by 
many users, animal protection organisations and those with a specific interest in alternatives. 
Development of this role including further guidance for it may be of value to contribute to the 
improvement  in  availability  of  relevant,  up  to  date  information  promoting  replacement, 
refinement and reduction, as well as species specific information. 

the  need  for  co-ordinated  and  focussed 

impact,  but 

Member State responses 

Are the persons identified in Article 24 (persons responsible for overseeing welfare, ensuring 
access  to  information,  and  education  and  training)  being  effective  in  their  roles?  Are  they 
contributing to the implementation of the Three Rs? 

71 

 
 
 
 
 
Yes 
No 
No opinion 
Too early to assess 

 15/28 
-/28 
1/28 
12/28 

Generally positive response, but too early to draw firm conclusions. 

Introduction of these key responsibilities seems to have prompted improved communication 
within establishments, among scientists, care staff and the AWB. 

Concerning  the  person  overseeing  welfare  and  care  of  animals,  in  many  cases  such  an 
individual was already in place previously thus no great change had been noted. When new, 
their co-ordination of technical input to refinement is considered in particular to be valuable. 

 

 “Training officer role has had a massive impact on refinement in terms of ensuring 
competency in the performance of procedures, therefore reducing suffering.” 

The  person  responsible  for  provision  of  information  seems  to  have  had  an  impact  on 
improving communication within establishments. However, there is some confusion over this 
role, in particular with input on scientific considerations. 

  “They are effective in their roles and contributing to the implementation of the Three 
Rs  by  e.g.  giving  advice  to  the  staff  on  matters  related  to  the  welfare  of  animals, 
the 
preparing 
implementation  of  the  animal  experiment  rules  of  the  institution,  organising  the 
education  and  training  of  the  personnel,  approving  the  experiments  prior  to  project 
evaluation, etc.” 

the  animal  experiment  rules  of 

institution,  controlling 

the 

  “Staff  devised  and  tested  a  novel  way  of  obtaining  saliva  samples  from  pigs  which 
removed  the  need  for  restraint  and  which  was  easy  to  train  the  pigs  to  use.    It  has 
been  scientifically  validated  and replaced the  need  for  some  authorised  procedures. 
In another establishment, A24 staff set up a series of seminars and organised a 3Rs 
day  for  staff  to  present  posters  of  3Rs  improvements.  The  staff  are  embedding  the 
refinements identified and the event has been made an annual event.” 

Additional guidance has been developed by some Member States to facilitate these roles.  

User responses 

Are  the  persons  identified  in  Article  24  (persons  responsible  for  overseeing  welfare, 
ensuring access to information, and education, training and competence) being effective in 
their  roles  and  contributing  to  the  implementation  of  the  Three  Rs  and  improved  animal 
welfare? 

72 

 
 
 
 
 
81% of user responses indicated that the persons identified in Article 24 are being effective. 

Of  those  who  did  not  think  that  these  persons  were  effective,  some  stated  that  the  systems 
were  already  in  place  before  the  new  Directive,  and  others  stated  that  they  needed  more 
training in aspects of science, or Three Rs and animal welfare.  

  Resources including Handbooks for Article 24 persons and others have been produced 
in  some  Member  States  by  a  number  of  organisations  (e.g.  LASA,  RSPCA14, 
UFAW15, NC3Rs16, IAT17).  

  Advanced  training  programmes  are  in  place  in  some  Member  States  for  the 
specialisation of veterinarians in laboratory animal science, and for the role of animal 
welfare  officer.  Training  courses  are  also  available  for  persons  responsible  for 
information. 

There  seems  to  be  some  misunderstanding  or  lack  of  knowledge  of  the  role  and 
responsibilities of the Article 24 person. 

Examples of good practice: 

 

Improvements in specific techniques and husbandry and care described 

  Better definition / monitoring / application of welfare endpoints 

  "Introduction  of  training  for  all  staff  in  their  specific  roles  /  Three  Rs  /  animal 

welfare" 

  "The organisation has prioritized funding for training of the staff." 

  "Participation  in  all  educational  courses  by  the  person  responsible  for  overseeing 
welfare and care, which leads to a good contact with new scientists and the care staff, 
reducing any reluctance to ask for help and support regarding animal welfare." 

14 https://www.rspca.org.uk/home 
15 https://www.ufaw.org.uk/ 
16 https://www.nc3rs.org.uk/ 
17 http://www.iat.org.uk/ 

73 

 
 
 
 
 
                                                            
  "Regular meetings for staff with the aim to improve knowledge and to give  ongoing 

education" 

  "Early discussion of experimental design" and "Involvement of Article 24 persons in 

construction of SOPs, and including welfare / husbandry details" 

  "Creation of internal website where all information on SOPs, best practices etc. can 

be found." 

  "Newsletters are distributed regularly" 

  "Implementation  of  Continuous  Professional  Development  plan,  in  some  cases 

including specific courses annually" 

  "Development of web based training materials" 

Recommendations  

  Where  not  yet  available,  Member  States  should  publish  minimum  requirements  for 
education and training, and for obtaining, demonstrating and maintaining competence, 
and increase efforts to disseminate EU and other guidance on education and training 
to  scientific  users  to  indicate  their  expectations  for  trained  and  competent  staff. 
National  guidance  should  be  shared  with  the  relevant  stakeholder  organisations  and 
other Member States. 

  Member  States  should  ensure  clarity  of  Article  24  roles,  in  particular  those  of  the 
training  and  information  persons,  to  ensure  effective  implementation  and  also  to 
increase  awareness  of  their  role  and  the  support  they  can  provide  within 
establishments. 

2.4 REUSE (ARTICLE 16) 

Article  16  of  the  Directive  lays  out  the  condition  for  reuse  of  animals.  Under  specified 
conditions  relating  to  the  severity  experienced  by  an  animal  in  previous  procedures,  reuse 
may be permitted. 

It is too early to determine whether there has been any significant impact as a consequence of 
these  new  requirements.  Also,  the  baseline  for  statistical  reporting  has  changed  and  thus  a 
detection of change in numbers is not possible at present. 

Member State responses 

Clarification  was  requested  from  Member  States  on  the  impacts  of  cumulative  severity  or 
reduction of animal numbers in connection with the reuse.  

74 

 
 
 
In  many  Member  States,  reuse  was  permissible  under  earlier  legislation,  but  the  new 
Directive  sets  out  new  obligations.  However,  there  is  yet  too  little  experience  to  determine 
whether there has been any significant impact as a consequence of these new requirements.  

Although  reuse  often  reflects  a  sensible  use  of  animals,  for  example  following  mild 
procedures  with  little  effect  on  the  animals,  a  number  of  comments  received  called  for  a 
considered balance of reduction and refinement i.e. use more animals of lower severity versus 
higher welfare harms to individuals undergoing reuse.  

Reuse is more common in routine production of, for example, blood products. 

In  response  to  whether  difficulties  had  been  encountered  with  the  provisions  of  Article  16, 
Member  States  requested  additional  practical  examples  on  reuse/continued  use  and 
clarification on reuse of surgically prepared animals. Also, additional guidance was requested 
on the assessment of “cumulative” severity.  

Other reported issues concerned clarity of “exceptional circumstances” in Article 16(2) – this 
is considered to cause unnecessary restriction on reuse.   

75 

 
 
 
 
 
User responses 

Have the new controls over reuse provided the correct balance between individual animal 
welfare and a reduction in animal numbers used? 

The highest response (41%) was from users who commented that their animals were always 
killed  at  the  end  of  study  to  obtain  tissues  for  analysis  and  reuse  was  not  therefore  a 
consideration. 

Of  the  remaining  responses,  20%  were  of  the  view  that  the  new  controls  provided  a 
reasonable balance, 11% disagreed and 15% thought it was too early to give a view. 

As  with  Member  State  responses,  further  clarity  on  reuse/continued  use  was  requested.  In 
particular,  use/reuse/continued  use  of  genetically  altered  animals  should  be  made  clearer. 
Difficulties were encountered with genetically altered animals that had gone through invasive 
genotyping as such animals could no longer be reused in “severe” procedures. Other similar 
examples  included,  a  single  blood  sample  from  dog  or  non-human  primate  would  preclude 
use later in a severe procedure.   

Assessment  of  severity  in  long  term  use/reuse  of  telemetry  animals  was  considered 
challenging. 

Recommendations 

  The Commission services and Member States should develop additional guidance on 

reuse.  

2.5 AVOIDANCE OF UNNECESSARY DUPLICATION (ARTICLE 46 AND ANNEX 
VI) 

The project evaluation and authorisation processes are the main methods of control imposed 
by  Member  States  to  ensure  compliance  with  Article  46  and  Annex  VI  which  lays  a 
requirement to avoid unnecessary duplication.  

Member  States  control  this  either  by  requesting  information  on  actions  taken  to  avoid 
unnecessary  duplication  or  by  legal  declarations.  A  single authority, responsible  for  project 

76 

 
 
 
 
 
evaluation for the entire Member State, has a good overview and is better positioned to detect 
unnecessary duplication than when there are multiple authorities.  

Improved communication, coordination and dissemination of information from key regulators 
is  requested  when  new  data  become  available  –  e.g.  European  Medicines  Agency  (EMA), 
European  Chemicals  Agency  (ECHA).  It  is  important  that  all  efforts  are  made  by  users  to 
actively access and consider current, already available information.  

Prompt publication and updating of non-technical project summaries, and a central searchable 
EU  tool  to  access  these  would  improve  availability  of  information  on  authorised  projects. 
However, there may be language issues to overcome. 

Member State responses 

 

 “Improved publication of all procedures using animals (also consider publication of 
Retrospective Assessments and Project Evaluations.” 

  “Searchable European database of all NTSs – would increase awareness and further 

improve transparency” 

  “National database of authorised animal studies.” 

User responses 

Across  all  sectors,  the  quality  of  experimental  design  and  execution  is  seen  as  essential  to 
produce good results first time, and  some AWB help scientists to achieve this; for example 
working  to  Good  Manufacturing  Practice  (GMP)  or  Good  Laboratory  Practice  (GLP), 
Standard Operating Procedures, meticulous record keeping. 

Some use internal databases to check for duplication. Some use EU wide databases and one 
included patent review. Others were clearly unaware of these resources. 

It is important to remember that there are cases where duplication is legitimate:  

  “Duplication  of  published  work  may  make  sense  if  1)  those  results  conflict  own  in 
vitro findings, 2) the experimental conditions in vivo are insufficiently revealed 3) the 
study  appears  dubious  for  other  reasons.  Publishers  should  demand  a  thorough 
description of the animal experiments to be published.” 

Some aspects are dealt with differently in different sectors: 

Academic  –  requirement  for  extensive  literature  review  around  their  specific  field  was 
reported  by  many  as  key  to  avoiding  duplication.  The  project  submission  should  document 
the  novelty  /  scientific  innovation  of  the  work.  In  some  Member  States,  applicants  must 
submit statements that there is no pre-existing duplicated research. In some cases, proposals 
are evaluated by specialists, so reducing the risk of duplication of procedures. In other cases, 
specialists are not available. 

77 

 
 
 
Some were of the view that there may be duplication in genetically altered animal production 
and breeding, but there is also evidence of good practice, such as sharing of lines, as well as 
significant sharing of tissues to avoid duplication. 

Commercial  –  tests  are  carried  out  to  satisfy  regulatory  requirements  such  as  those  in  the 
European  Pharmacopoeia,  in  some  cases  including  batch  testing  (necessary  duplication). 
Seeking regulatory  and expert advice was seen by some as  important in this area including 
communication  with  sponsors  and  specific  regulatory  authorities.  Monitoring  regulatory 
developments was reported as important. Some search for commercially available sources of 
product before undertaking animal use. 

Comments 

  “We're  a  Contract  Research  Organisation  (CRO),  so  we  do  what  our  clients  order 
from us. We do not know which drug candidates they're developing, so if two clients 
would  have  the  same  drug  candidate  in  testing,  we  would  not  know  that.  However, 
this seems highly unlikely.” 

  “We need to trust in our customer, that a planned project was indeed not performed 
previously,  since  we  are  unable  to  review  their  data,  if  they  are  not  already 
published.” 

Good practice 

  “Regulatory  authorities  may  request  a  repeat  of 

these 
circumstances, we always request formal documentation from the client as to why a 
repeat study is required.” 

in-vivo  studies.  In 

  “Weekly  exchange  of 

information  between  MSs  (Official  Medical  Control 
Laboratories  -  OMCLs)  on  future/intended  testing  (e.g.  Official  Control  Authority 
Batch Release) and acceptance of results of testing performed by OMCL of other MS”  

Problems included 

  “Projects authorised in one MS are not recognised in other MS which is an obstacle 
to free exchange in EU environment. This situation unfortunately drives additionally 
to avoidable duplication of procedures” 

Some clarification is needed to differentiate duplication (the same study design to answer the 
same  scientific  aim)  and  replication  (the  same  study  design  to  test  the  reproducibility  of 
results) and the reasons for batch testing as part of the regulatory process. 

A suggestion was that non-technical project summaries should be made available across all 
Member States in a searchable database (see more in section 3.1). 

78 

 
 
 
Recommendations  

  Member  States  should  re-enforce  the  awareness  of  the  need  for  researchers  and 
project evaluators to ensure that no unnecessary duplication takes place, in particular, 
in the development of new genetically altered animal lines. 

2.6 SETTING FREE AND REHOMING (ARTICLE 19) 

The  provisions  of  Article  19  allow  animals  used  or  intended  for  use  to  be  rehomed,  or 
returned to a suitable husbandry system or to be set free to a suitable habitat subject to health 
and welfare safeguards.  

Rehoming is new to many Member States, with establishments now aware of the possibility 
that animals may be rehomed at the end of procedures. Around 50% of Member States have 
changed policies on rehoming due to changes in the Directive. 

Although many Member States have alerted establishments to this practice, it seems that only 
very few animals are affected. There are little quantitative data on numbers and there is no 
legal obligation for collection or collation of numbers of animals set free or rehomed. 

Users reported that rehoming is not suitable for the majority of animals and species used in 
procedures as, for example tissues/samples are required on completion of studies. 

Although  additional  guidance  was  requested  by  some  respondents,  some  guidance  has 
already been prepared by Member States and interested organisations. 

Member State responses 

Did the policy on re-homing in your Member State change with the new Directive (e.g. not 
done previously, now actively promoted? 

Yes 
No 
Not applicable 

 14/28 
 7/28 
 7/28 

Have  the  number  and  type  of  animals  being  rehomed  changed  with  the  introduction  of  the 
Directive? 

Yes 
No 
No opinion/NA 

 7/28 
 9/28 
 12/28 

Rehoming was reported for only a few dogs and even fewer rabbits.  

A  number  of  Member  States  indicated  that  farm  animals  were  being  set  free  or  "rehomed" 
where  such  animals  were  being returned to  farms for agricultural practices.  The title of the 
Directive provision is confusing for some users and stakeholders. 

79 

 
 
 
 
 
 
80 

 
 
 
 
 
User responses 

Has the Directive resulted in a new or amended policy on rehoming in your establishment? 

Has the new / amended policy been effective in facilitating suitable animals to be rehomed? 

The user responses indicate that very few have been affected by the changes to the legislation 
regarding rehoming. There are also difficulties reported in identifying “homes” or places for 
adoption, and long term costs can be an issue e.g. non-human primates. Additional guidance 
was requested.  

Responses  varied  as  many  clearly  had  existing  policies  which  either  have  not  significantly 
changed  or  been  made  clearer,  although,  in  a  few  cases  reported  as  being  apparently  more 
difficult. Where no policy existed previously there were reports of some increased numbers 
being rehomed, mostly for larger species with many stating that rehoming rats and mice was 
difficult. For many others rehoming is not appropriate because of the nature of the science, 
and  the  need  for  tissues  at  the  end  of  the  procedure,  or  legal  constraints  e.g.  legislation  on 
genetically modified organisms. 

Recommendations  

  Where  appropriate,  Member  States  should  share  relevant  guidance  material  on 
rehoming,  as  well  as  make  use  of  guidance  developed  by  other  Member 
States/stakeholder organisations.  

81 

 
 
 
 
 
 
 
2.7 SHARING ORGANS AND TISSUES (ARTICLE 18) 

Sharing  tissues  should  reduce  the  numbers  of  animals  used  and  therefore  have  welfare 
impacts by the reduced use of animals. Article 18 of the Directive calls for Member States to 
facilitate,  establishment  of  programmes  for  the  sharing  of  organs  and  tissues  of  animals 
killed.  

For  some  users,  tissue  sharing  has  been  available  for  a  long  time,  e.g.  EUPRIM-Net18, 
AniMatch19, ShARM20, European Xenopus Resource Centre21. These initiatives which have 
been set up across Europe for the sharing of tissues, appear not to be sufficiently well known 
throughout the scientific community. 

In some Member States, a legislative requirement is included that requires establishments set 
up a tissue sharing framework and its impact is assessed during Inspections. Few systems are 
coordinated  by  Member  States,  but  one  Member  State  reported  that  it  has  a  National 
Telematics Data Bank. National Three R centres are taking an interest in this issue.   

Users  responded  that  the  requirements  in  the  Directive  have  heightened  the  need  and 
importance  to  do  this  to  make  best  use  of  animals  and  reduce  numbers.  AWB  in  some 
establishments  have  taken  the  lead  to  develop  an  effective  communication  strategy,  and 
exchanges between establishments are also in place.  

Many  who  used  tissue  sharing  stated  that  this  had  reduced  the  numbers  of  animals  used 
overall.  

Concerns were raised by some over the difficulties in moving tissues between Member States 
(due to health and safety issues). 

Member State responses 

Few systems are coordinated by Member States, but the practise is encouraged and promoted 
at establishments.  

Included  in  legislative  requirement  in  some  Member  States  is  a  requirement  for 
establishments  to  institute  a  tissue  sharing  framework  and  its  impact  is  assessed  during 
Inspections. 

Have  these  measures  been  effective  in  reducing  the  number  of  animals  needed  to  meet 
demands for tissues and organs? 

Yes 
No 
No opinion/NA 
Too early to assess 

 5/28 
 -/28 
10/28 
9/28 

18 http://www.euprim-net.eu/  
19 https://www.animatch.eu 
20 https://www.sharmuk.org  
21 https://xenopusresource.org/  

82 

 
 
 
                                                            
No answers 

4/28 

It is too early to draw any conclusions on the impact on numbers but some indications that 
active funding to promote measures at national or EU level would be helpful. 

Good practice was noted requiring tissue users in establishments to confirm to internal AWB 
that efforts have been made to obtain tissues by sharing. 

83 

 
 
 
 
 
 
User responses 

What measures have been taken at establishment level to promote the sharing of organs and 
tissues? Have these measures been effective in reducing the number of animals needed to 
meet demands for tissues and organs? 

Tissue sharing was an established practice in some establishments before the new Directive 
requirements,  generally  for  the  larger  species,  for  example  dogs,  non-human  primates  and 
farm species, driven primarily by cost. 

The  requirements  in  the  Directive  have  heightened  the  need  and  importance  to  do  this  to 
make best use of animals and reduce numbers. AWB in some establishments have taken the 
lead to develop an effective communication strategy.  

Good practice 

  Good  communication  between  researchers  and  animal  care  staff  within  the 
establishment  is  reported  as  essential.  Suggestions  and  recommendations  may  be 
made by the AWB. 

 

Including a question on sharing of tissues as a standard question in the submission for 
ethical consent approval is required by at least one establishment. 

  Cryopreservation of well characterised tissues including tumours was reported. 

  "Announcing  planned  animal  killing,  in  one  establishment  by  an  internal  calendar 

assists planning."  

  "The creation of a common experimental histology facility where the person in charge 

can centralize samples and co-ordinate the needs of different users." 

  "Central management for Xenopus and Zebrafish embryo production allows reduction 

in the numbers" 

  "Including as part of the routine health monitoring and pathology program. Various 
tissues are sampled and in some cases stored frozen and available free of charge to 
the  scientific  community,  internally  including  geographically  remote  sites  and 
externally in some cases." 

  "After some surgery courses on animals, organs are collected for other use, e.g. eyes, 

skin and gut for ex vivo surgical training, or basic research." 

Less good practice 

 

Information  on  the  availability  of  genetically  altered  animal  lines  is  very  variable 
between researchers. 

  "The researchers work too much alone / too individualistically to share" 

84 

 
 
 
 
 
  "There  still  remains  some  fear  from  researchers  about  sharing  information  about 

their work" 

Difficulties 

  "Tissues are not always prepared in the same / an appropriate way." 

  "Tissues  deteriorate  rapidly  without  appropriate  collection,  preservation  and 

storage." 

  "Some  authorisations  seem  to  require  specific  statements  of  sharing,  or  other 

legislation maybe limiting sharing e.g. transport or safety legislation." 

  "Complex bureaucratic procedures for the transport of organs and tissues, including 

import / export (health/safety requirements)." 

  "Sharing  is  not  always  possible  due  to  use  of  infective  agents  or  radioactivity,  or 

different health status of animals affecting relevant tissues." 

  "Tissues are not always available at the right time." 

  "Appropriate communication outside establishment is not in place." 

  "Costs of running sharing schemes." 

2.8 USE OF EXISTING ALTERNATIVE APPROACHES AND IMPLEMENTATION 
OF THE THREE RS 

2.8.1 The role of project evaluation in the use of alternative approaches and 
implementation of the Three Rs 

With  regard  to  the  Three  Rs  and  animal  welfare,  half  of  the  user  respondents  felt  that  the 
introduction  of  project  evaluation,  with  advice  provided  during  the  evaluation,  had  had  a 
positive impact on animal welfare. Examples included the improved use of analgesia, more 
clearly defined endpoints, and more refined protocols (reduced harm to animals). The use of 
literature searches including Three Rs elements were reported to be more overt, and included 
the identification and subsequent application of various specific refinement guidelines. 

Indirect improvement to animal welfare included a reduction in numbers used, due to better 
project designs or by replacement of animals using alternative methods. Several commented 
that the Directive had created an increased focus on the Three Rs, and improved justification 
for  the  procedures  used,  which  is  suggestive  that  there  could  be  a  reduction  in  animal  use 
realised in due course. For many users, similar processes were in place before the Directive, 
and so no significant changes or improvements have been seen since implementation. 

A number of aspects of the new Directive are aimed specifically at improving animal welfare 
and requiring effective implementation of the Three Rs in the use, care and breeding animals 

85 

 
 
 
 
 
for scientific purposes. Guidance developed at EU for Severity Assessment Framework22 has 
been especially useful in promoting the concept of continuous refinement; the consideration 
of severity and the ways in which it can be minimised within the initial study design, through 
the  study-specific  day-to-day  monitoring  of  animals  during  the  project,  to  the  “actual” 
severity  assessment  upon  completion  of  the  study.  A  number  of  successful  workshops  on 
promoting  consistent  interpretation  and  application  of  the  severity  framework  have  been  in 
held,  coordinated  by  FELASA,  with  the  support  of  Member  State  authorities,  involving 
scientists, veterinarians, care staff, regulators and inspectors. 

There  is  a  positive  response  among  users,  Member  States  and  scientific  stakeholder  groups 
that the Directive has improved the application of the Three Rs, in particular in the area of 
project evaluation and authorisation. The level of impact varies among Member States but the 
positive  impact  is  greater  in  those  countries  which  previously  did  not  have  a  project 
evaluation and authorisation processes in place.    

In contrast, animal protection organisations generally disagree that the increased focus on the 
Three Rs and project evaluation processes benefitted animal welfare. 

Member State responses 

Many elements within the Directive require consideration of the Three Rs. Have these been 
effective? 

Yes 
No 
No opinion 
Too early to assess 

 17/28 
 1/28 
 -/28 
10/28 

Has the requirement to comply with the Three Rs had an impact on animal procedures? Has 
it improved the design of procedures and/or projects? Has it improved animal welfare? 

Yes 
No 
No opinion 
Too early to assess 

18/28 
 2/28 
 2/28 
6/28 

The main positives indicated by Member State submissions include the improved designs of 
projects, more careful consideration and application of the Three Rs, obligatory independent 
evaluation  process,  severity  classification  and  implementation  of  humane  end-points  and 
contributions by AWB at each establishment. 

  "Although too early to assess, the establishment of animal welfare bodies is foreseen 
to  have  a  positive  impact  on  the  general  awareness  of  the  3Rs.  In  addition,  the 
requirement of the non-technical summaries highlights the need to apply to the 3Rs." 

22 http://ec.europa.eu/environment/chemicals/lab_animals/pdf/guidance/severity/en.pdf 

86 

 
 
 
 
 
                                                            
  “There  is  a  need  for  improved  communication,  coordination  and  dissemination  of 
information - key regulators should better publicise when alternatives accepted – e.g. 
EMA ; ECVAM “ 

87 

 
 
 
 
 
User responses 

Has there been an impact from the introduction of the requirement for systematic project 
evaluation on animal welfare in your establishment? 

Of those who answered, the impact of the project evaluation and authorisation processes in 
France seems to have been greater than in other countries. 

No 
Yes 
Too early 
No opinion/NA 
Total responses 

All users 

France 

No 
207 
417 
117 
92 
833 

% 
25% 
50% 
14% 
11% 
100% 

No 
67 
189 
30 
14 
300 

% 
22% 
63% 
10% 
5% 
100% 

Rest of EU 
% 
26% 
43% 
16% 
15% 
100% 

No 
140 
228 
87 
78 
533 

The  impact  can  be  interpreted  as  positive  in  terms  of  improved  experimental  design  and 
consideration  of  Three  Rs  or  negative  as  increased  bureaucratic  burden.  Analysis  of 
responses relies on the comments. 

Project  evaluation  has  had  a  greater  impact  in  Member  States  which  did  not  have  a 
requirement previously.  

Many  who  stated  that  the  Directive  had  no  impact  judged  that  the  previous  legislation  in 
place had already applied the Three Rs, unlike some who stated that it had served to reinforce 
this.  

Of  those  suggesting  that  the  Directive  had  had an  effect  on  the  Three Rs,  some  considered 
that  the  requirement  for  project  evaluation  with  better  definition  of  expected  effects  and 
endpoints, along with discussion of these issues with others (animal care staff, AWB, project 
evaluators)  had  refined  procedures.  Several  felt  there  was  better  use  of  analgesia,  or  better 
controls over reuse. Better definition of what the AWB should achieve through the additional 
EU guidance was thought to have assisted. 

88 

 
 
 
 
 
  
  
 
For  some,  there  had  been  an  improvement  in  animal  housing  conditions  including 
enrichment, group housing and the use of positive reinforcement. 

Others  felt  that  there  was  better  experimental  design  as  a  result  of  the  project  evaluation 
process,  including  consultation  with  a  statistician  and  consideration  of  appropriate  control 
groups.  

Some have been able to introduce alternative methods and some respondents stated that there 
has been increased sharing of tissues. 

Many suggested that better education of staff with assurance of competence is improving the 
Three  Rs.  The  requirement  for  a  Designated  Veterinarian  contributed  to  reinforcement  of 
good practices in surgery, anaesthesia, analgesia and euthanasia. 

There  are  also  external  drivers  and  constraints  on  the  application  of  the  Three  Rs.  Several 
respondents  stated  that  Three  Rs  were  not  possible  to  apply  as  there  was  a  regulatory 
requirement for the testing performed in a particular way. There were also a few comments 
that publications require in vivo models or numbers of animals which were higher than those 
determined locally. 

Comments 

  "The  requirement  of  a  project  authorization  encourages  researchers  to  think  about 
the  design  of  their  experiments:  the  reflection  on  the  number  of  animals  and  the 
statistical approach upstream." 

  "Our  national  authorities  issued  in  2014  a  new  template  for  project  evaluation,  in 
which more attention is paid to 3Rs.  At the same time, the ethical committees were 
expanded  to  a  minimum  of  7  members  (with  at  least  two  external  members),  with 
expertise or competence in ethics, alternative methods, animal health, animal welfare, 
research techniques, study design and statistical analysis. This led to a more balanced 
review." 

  "Systematic  project  evaluation  was  already  in  place  prior  to  the  directive,  and  the 
three R’s were already used at the basis of the project evaluation. What has improved 
over the years is that the forms that were used for the project evaluation have evolved 
to  pay  more  explicit  attention  to  the  three  R’s.  Also,  the  improved  focus  on  correct 
statistics has had its impact, even though this has not always led to a reduction in the 
number of animals." 

  "An important administrative change in a country where the project authorization via 
an  ethical  committee  was  not  in  the  law  but  on  a  voluntary  base.  The  project 
authorization was very positive for research studies. It has obliged us to better define 
the study design and limit some experiments." 

89 

 
 
 
  "Project  evaluation  has  led  to  the  development  of  user  groups  and  the  sharing  of 
good/best  practice.    This  has  led  to  significant  refinements  in  some  cases,  better 
record keeping and monitoring regimes and also shared resources." 

  "We  don't  see  an  improvement  due  to  the  requirement  for  project  evaluation 

compared to our SOPs beforehand." 

  "Much  of  the  guidance  is  directed  at  rodents,  with  little  information  on  the  less 
common species such as farm animals and fish. There are challenges in dealing with 
unusual species." 

  "Additional  guidance  requested  on  conflict  between  reduction  and  refinement 

regarding severity and severity thresholds including GA phenotypes." 

  "The  introduction  of  these  requirements  has  increased  the  time  necessary  to  the 
preparation  of  protocols  but  had  the  merit  of  ensuring  a  much  deeper  reflection  of 
many technical aspects. More internal debate to find better solutions to improve the 
quality of the project." 

  "Better statistical evaluation of the minimum animal number required for the study 

Better attention to animal care and to reduce animal suffering" 

  "Because  of  systematic  project  evaluation,  researchers  need  to  design  the  entire 
projects  before  the  beginning  of  the  projects.  Consequently,  the  number  of  animals 
can  be  optimized  and  reduced  and attention can  be  paid  to  animals  used  in  several 
procedures." 

Stakeholder organisations 

Systematic project evaluation and project authorisation has improved the implementation of 
the Three Rs and welfare of animal in my country/region. 

All stakeholders 

90 

 
 
 
Other stakeholder organisations 

Animal protection organisations 

Other stakeholder comments 

Scientific stakeholder groups acknowledge the need for robust processes to ensure effective 
application of Three Rs within a project. Impact varies significantly dependent on previous 
Member State legislation. 

  "Project authorisation, where not in place previously, is expected to have a positive 
impact  on  the  implementation  of  the  3Rs.  The  requirements  to  explain  more  clearly 
the harms to animals and information on the 3Rs in applications have already had an 
impact on planning and executing studies." 

  "Systematic Project evaluation and authorization process led the Licence Holders to 
revise  the  way  to  present  and  explain  their  project  and  the  experimental  protocols, 
increasing the awareness that the use of animals for experimental purposes is allowed 
only if no other alternatives are available" 

  "This  is  too  early  to  say  how  much  is  improved  in  practice.  The  awareness  of 
Refinement and animal welfare has increased a lot- this is very positive thing. No real 
effect seen in projects on implementation of replacement methods to decrease animal 
tests". 

  "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 

91 

 
 
 
 
 
 
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." 

Animal protection stakeholder comments 

In  contrast  to  the  generally  positive  views  of  Member  States,  users  and  other  stakeholder 
groups,  the  animal  protection  groups  expressed  significant  concerns  over  the  impact  of 
project evaluation and authorisation on Three Rs implementation. The main concerns relate 
to  the  transparency  of  the  process,  and  that  all  projects  are  authorised.  One  response 
suggested  that  in  one  Member  State  no  harm-benefit  was  included  within  the  national 
legislation.    

  "We need better transparency of projects in order to make an informed opinion. We 
are  concerned  that  a  great  number  of  severe  experiments  are  still  being  licensed. 
Also, It is unclear how 3Rs are being considered and what priority is given to animal 
welfare." 

  "Project  evaluations  tend  to  use  the  same  arguments  and  hollow  phrases  to  justify 
animal use from one application to another. Very little in-depth analysis is shown in 
any individual project to argument its case. Authorization is always granted." 

  Related  to  one  Member  State  "According  to  law  the  authorities  don’t  have  the 
possibility  to  balance  the  harm-benefits.  They  can  only  check  applications  formally 
but not reject an experiment for ethical reasons. The result  is that even most severe 
and frivolous experiments are being authorized." 

  "There  is  a  lack  of  transparency  on  the  evaluation  &  authorisation  process.  It  is 
generally unclear how 3Rs are being considered and what priority is given to animal 
welfare." 

  "All  the  projects  get  authorized  which  reveals  the  system  lacking  real  judgement  as 

the outcome is already set in the beginning." 

2.8.2 Use of existing alternative approaches 

The  term  ‘alternatives’ in  this  context  includes  all  assays, tests,  methods,  techniques,  tools, 
strategies and approaches etc. that contribute to the practical implementation of the Three Rs, 
that is to 

  obtain the required information without the use of live animals; 
  use fewer animals whilst obtaining the same level of information; 
 

improve  the  way  procedures  are  carried  out  so  as  to  cause  less  pain,  distress  or 
suffering, or improve the welfare of the animals 

The  Directive  makes  a  firm  legal  obligation  on  scientists  and  establishments  that  animal 
procedures  may  only  be  carried  out  when  there  are  no  non-animal  methods  available  to 
achieve  the  scientific  objective.  Alternative  approaches  are  promoted  in  a  number  of 

92 

 
 
 
provisions in the Directive, for example Articles 4, 13, 27, 38 and 49, promoting focus on the 
application of the Three Rs at project, establishment and national level. Whereas Article 13 
makes  a  specific  obligation  to  use  recognised  alternatives  in  the  regulatory  testing  context, 
Article  4  ensures  that  the  legal  obligation  to  use  alternative  approaches  covers  all  areas  of 
animal use. 

In  many  Member  States,  specific  information  is  requested  during  the  project  application 
process, for example information on searches, choice of model and design of study. These are 
reviewed by project evaluators. Declarations and conditions of authorisation are also used to 
confirm  that  the  Three  Rs  will  be  subject  to  continuous  review  during  the  period  of 
authorisation.  

A  few  Member  States  highlighted  the  importance  of  inspection  programmes  to  verify 
compliance with the Three Rs and the continued application of new alternatives throughout 
the life of the project (necessitating that inspectors are trained and current on developments in 
Three  Rs  and  alternatives  opportunities).  As  part  of  the  project  submission  and  evaluation 
process, the Directive requires that scientists consider and document whether their work can 
be  done  without  the  use  of  live  animals,  such  as  applicants  checking  alternatives’  websites 
prior to project application.  

Of  the  scientists  who  responded,  a  third  agreed  that  the  Directive  has  increased  the  focus, 
activities  and  resources  aimed  at  alternatives.  Examples  of  where  alternatives  had  been 
adopted  included  the  use  of  cell  lines  as  a  part  of  many  work  programmes.  Some 
establishments stated that they include training in cell culture methods for all scientists.  

Animal  protection  organisations  requested  simple  effective  mechanisms  to  promote  uptake 
and communication/dissemination of alternatives, in particular, in fields other than regulatory 
toxicology. 

Member State responses 

How do competent authorities ensure alternatives are used wherever possible (Article 4 and 
13), including adaptation to technical progress during the life cycle of a project? 

Member States have adopted a number of measures to ensure that alternatives are used where 
available  and  appropriate  for  the  scientific  study.  The  project  evaluation  and  authorisation 
processes  are  considered  the  main  pillars  to  ensure  that  alternatives  are  given  due 
consideration. Although the applicant is expected to know the availability of alternatives, the 
evaluation  process  should  engage  sufficient  expertise  to  confirm  that  indeed  there  are  no 
alternatives possible within the proposed programme of work. 

Authorised projects often explicitly state the requirement that alternatives be adopted as these 
became available. 

AWB  have  oversight  of  the  Three  Rs  within  establishments  and  are  expected  to  advise 
project authorisation holders of relevant new developments in alternatives. 

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Retrospective assessment is expected to provide a further opportunity to consider the Three 
Rs, but impact is too early to assess. 

User responses 

Users  echoed  the  need  for  better  communication,  easier  searching  methods,  and  better 
availability  of  information  on  alternatives.  The  role  of  the  information  person  (Article 
24(1)(b)) is still evolving, but assistance in searching and keeping establishments up-to-date 
on  alternative  methods  would  help  to  fill  a  gap  recognised  in  a  number  of  user  responses. 
AWB  have  oversight  of  the  Three  Rs  within  establishments  and  are  expected  to  advise 
project  authorisation  holders  of  relevant  new  developments  in  alternatives  (Article  27(d)). 
This can be achieved, for example, through individual communications, newsletters or Three 
R  seminars.  However,  some  AWB  do  not  seem  as  yet  to  have  developed  information 
dissemination strategies within their establishment. 

Many  users  were  of  the  view  that  Member  States  had  some  obligation  to  inform  users  of 
developments  in  alternatives,  in  particular  as  project  authorisation  holders  will  be  held 
responsible should these not be applied appropriately. 

Many agreed that it was difficult to assess the impact of these activities to promote alternative 
strategies. There has been no apparent reduction in animal use to date, but it may take some 
time  for  reductions  due  to  introduction  of  alternatives  to  become  apparent.  Some  specific 
cases  by  responses  from  a  few  individual  users  contradicted  this  perception,  identifying 
examples where significant reductions had been effected by the use of alternative methods. 

Users  indicated  that  studies  on  some  aspects  of  biology  such  as  conscience  and  vigilance 
states, reproduction, and developmental biology continue to need in vivo experimentation and 
alternative methods are unlikely to be available in the foreseeable future.  

It  is  also  the  case  at  this  time,  that  the  European  Pharmacopoeia  /  chemicals  registrations  / 
other regulations require the use of animal studies and therefore changes in other legislative 
areas are required before reliance on alternatives in these fields can be achieved. 

The Directive has increased the focus, activities and resources aimed at the development, 
validation and uptake of alternative approaches. 

94 

 
 
 
30% of the user responses suggested a positive impact of the Directive on an increased focus 
on alternatives. 24% neither agreed nor disagreed, 10% disagreed and around 34% had either 
no  opinion  or  of  the  view  that  it  was  too  early  to  tell.  The  Directive  is  one  factor  driving 
alternatives,  but  scientific,  ethical  and  economic  factors  are  also  important  elements. 
Scientists want to do the best science and only use animals when necessary. In some research 
fields there have been more advances than in others, but there will be a continued need for 
animals  for  some  years  to  come.  Regulatory  requirements  still  demand  animal  testing,  and 
alternative validations can take a long time. 

Some requested an easier searching method, better availability of information on alternatives 
and  experts  to  help  find  them  relevant  to  the  field  of  work.  The  mandatory  training  now 
required will improve knowledge on alternative strategies. 

  “Many  experiments  are  now  made  on  cell  lines,  and  some  establishments  include 

training in cell culture methods for all scientists.” 

  “There  have  been  development  and  validation  (in  some  cases)  of  non-invasive 
methods  in  ecotoxicology,  development  of  PCR  methods  in  replacement,  3D  co-
cultures for toxicity studies.” 

  “Teaching  animals  are  supplemented  and,  if  possible,  replaced  by  simulator-based 

training” 

  “Project applicants encouraged to check alternatives website prior to AWB review.” 

  “There is much evidence of alternative development within ECVAM of the number of 

methods in validation phase.” 

Obstacles to using alternatives included 

  Lack of knowledge/awareness of alternatives. 

95 

 
 
 
 
 
  “Scientist who work with non-animal methods do not get in contact with the animal 
facility.  Also,  knowledge  about  non-animal  methods  is  lacking  in  staff  advising 
scientists using animal models.” 

  “Generally, there are not much alternative approaches available in our field of work 

(eg systematic neuroscience).” 

  “Our experiments are regulated by the European Pharmacopoeia.” 

 

 “The  use  of  animals  is  most  of  the  time  more  expensive  than  alternative 
methodologies.  And  using  animals  when  it  can  be  done  other  way  is  distasteful. 
Economic  forces  and  ethical  considerations  were  driving  the  development  of 
alternative approaches before the new Directive.” 

  “The Directive has further increased the focus on 3Rs, which were however already 
embedded  in  our  institute's  culture.  A  practical  problem  is  the  fact  that  most 
resources or databases are for regulatory testing or educational purposes.  There is 
little available for more fundamental, basic research.” 

Stakeholder responses 

The  Directive  has  increased  the  focus,  activities  and  resources  aimed  at  the  development, 
validation and update of alternative approaches. 

All stakeholders 

Other stakeholder organisations 

Animal protection organisations 

96 

 
 
 
 
 
 
As many organisations agree as disagree on the impact of the Directive on alternatives. 

A higher proportion of animal protection organisations are of the view that the Directive has 
increased the focus on alternatives. 

There  should  be  improved  communication  on  acceptance  of  alternatives,  ensuring  that 
establishments are informed. 

It was felt that there was significant scope for the replacement of animals used for education 
and training purposes, with many alternatives available, but these do not seem always to be 
taken  up.  Reasons  for  this  were  similar  to  those  given  for  alternatives  in  other  areas,  but  it 
was  felt  that  solutions,  especially  in  the  area  of  education,  might  be  more  readily  available 
than in other fields, and that a themed review, and specific support/guidance, and/or targeted 
inspection could be beneficial. 

Animal protection stakeholder comments 

  "The  increase  in  non-animal  technologies  has  not  translated  into  a  reduction  in 

animal use." 

  "MS are not supporting the development of alternatives (Article 47). ECVAM and the 
Commission  and  are  not  validating  and  implementing  alternatives  in  a  timely 
manner." 

  "Profile  of  3Rs  has  increased  in  EU,  but  this  is  not  leading  to  substantial  enough 
changes in practices, impacts or a fast take up of new approaches.  It is unfortunate 
that  Art.  13  only  prohibits  animal  use  when  an  alternative  method  'is  recognised 
under the legislation of the Union’ (only likely to apply to reg. toxicology). There is 
little  evidence  EURL  ECVAM  is  more  effective/  better  funded  now  than  under  Dir. 
86/609/EEC." 

  "More  needs  to  be  done  in  general  to  make  sure  the  legal  obligation  to  use 
alternatives is implemented and to shift the emphasis from using animal models as the 
gold standard against which alternatives have to be validated." 

  "The competent authority should notify the scientific community of the acceptance of 

the alternative methods" 

Other stakeholder comments 

  "Alternatives to animal research was already on the focus within national legislations 
and regulations, but the Directive strengthens their position and contributed that the 
involved entities gained a higher attention and better funding opportunities." 

  "The  Directive  per  se  has  clearly  increased  focus  on  3Rs,  but  with  limitation  to 
establishment  /  project  level.  Nevertheless,  individual  initiatives  to  develop  and 
validate alternative approaches are too limited. Huge efforts are still needed in terms 

97 

 
 
 
 
of scouting, supporting, funding, inter-connecting and valuing such initiatives. It is a 
multi-player  challenge  where  EU  and  national  authorities,  3Rs  centres  need  to 
increase connections and communication, with the whole research community." 

  "Centres  for  alternatives  have  been/are  in  place  in  many  member  states,  but 
international  validation  of  those  is  painfully  slow  and  the  focus  on  development, 
validation  and  uptake  of  alternative  approaches  seems  not 
to  have  been 
implemented." 

  "Few reports of new alternatives arising as a result of the Directive per se.  Instead 
advances in alternatives have been driven by usual process of scientific curiosity and 
research" 

  "Lack  of  resources  aimed  at  development,  validation  and  uptake  of  alternative 

approaches were reasons for those siting disagreement" 

Responses from the organisations with a specific interest in alternatives 

The responses from the organisations with a specific interest in alternative methods identified 
a  number  of  key  issues  hindering  the  uptake  of  alternatives.  These  can  be  grouped  into 
categories  of  lack  of  knowledge,  poor  communication/dissemination  of  information, 
acceptability, and cost. 

Lack of knowledge / availability of information 

There  is  scope  for  improvement  of  the  knowledge  and  dissemination  of  what  information 
there  is  available  on  non-animal  and  other  alternative  methods,  and  their  applicability  and 
validity,  in  order  to  improve  the  breadth  of  options  for  scientists  to  consider.  A  single 
searchable European-wide database with better training on its use and updating of resources 
to upskill searching strategies were indicated as desirable outcomes. There is evidence of this 
knowledge  transfer  occurring,  but  it  needs  to  be  extended,  perhaps  moving  from  a  passive 
status  e.g.  by  publishing  on  Three  Rs  websites  to  a  much  more  active  communication 
programme  of  for  example,  thematic  reviews  and  following  through  by  assisting  in  the 
implementation process, and development of training resources on alternatives applicable for 
various levels of knowledge from school through to field -specific science areas.  

Acceptability 

Issues of acceptability are a significant hurdle. This can be from scientists who prefer to use 
traditional and well accepted ways using animals to answer their scientific questions. There 
are  also  expectations  of  peers,  reviewers  and  editors,  who  may  be  reluctant  to  accept 
alternative  methods.  If  an  alternative  method  becomes  available  it  may  be  difficult  to 
correlate  historical  data  with  the  new  method.  Regulatory  requirements  will  continue  to 
require  the  use  of  animals,  until  specified  alternatives  or  other  strategies  for  obtaining  the 
necessary  information  are  validated  and  clearly  applicable  in  that  domain.  Getting  a  new 
method  validated  and  accepted  across  different  regulatory  authorities  and  geographical 

98 

 
 
 
 
regions  can  be  challenging,  and  fear  of  not  having  the  alternative  test  accepted  as  valid  in 
these cases forms a significant hurdle to their early adoption. It is important that all relevant 
stakeholders  are  involved  in  validation  processes  to  ensure  that  the  tests  are  broadly 
acceptable or that the limits to the applicability domains are clear. 

Cost 

The complexity of some of the alternative methods can require significant investment, both in 
equipment, training and in-house validation, and ready access to consultants with high levels 
of  knowledge  in  these  techniques  is  not  good  currently.  There  may  be  scope  for  reviewing 
existing  resources  and  opportunities  for  networks  to  share  in  a  more  co-ordinated  manner, 
especially  in  the  education  and  training  sector.  There  were  several  requests  for  the  funding 
bodies  to  be  sympathetic  to  the  development  of  methods  and  to  training  in  alternative 
methods, and indications that some such resources are already available. 

Future Progress Required 

Respondents  indicated  a  significant  role  for  AWB,  project  evaluators  and  competent 
authorities  to  challenge  the  necessity  of  the  use  of  some  animal  models  when  alternatives 
exist. Whilst there is an onus on the scientists to show why the alternative method cannot be 
used,  including  in  non-technical  project  summaries,  there  is  scope  for  the  alternative 
“developers”  to  define  the  uses,  limitations  and  current  status  of  acceptability,  as  is  being 
done  on  the  EURL  ECVAM  Tracking  System  for  Alternative  Test  Methods  (TSAR)23 
database.  

EURL ECVAM has a valuable role in co-ordinating validations and maintaining databases of 
information on existing alternatives. There is scope to extend these activities and to provide 
advice on these issues, and co-ordinate other work in these areas including that done by the 
national  Three  Rs  centres.  Several  databases  are  available  including  DataBase  service  on 
Alternative Methods (DB-ALM)  24 providing information on alternative methods and TSAR 
showing progress from proposal through validation through to adoption and inclusion in into 
the regulatory framework. 

EURL ECVAM have also produced a user-friendly Search Guide to inform and support users 
to  find  high  quality  information  on  alternative  methods  and  are  investigating  sharing 
opportunities  to  accelerate  progress  in  Three  Rs  in  basic  research, toxicological  testing  and 
for education and training purposes. 

The National Committees can have a role in collecting, collating and disseminating progress 
in  the  area  of  alternatives,  and  international  collaboration  would  be  valuable  to  increase 
global awareness 

Three R developments in the use of non-human primates 

23 https://tsar.jrc.ec.europa.eu/ 
24 https://ecvam-dbalm.jrc.ec.europa.eu/ 

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More focus has been directed at the use of non-human primates under the Directive, and only 
where well-justified on scientific grounds and no other alternative exists, is the use of non-
human primates authorised. 

Drawing  from  the  SCHEER  Opinion  and  the  responses  received,  some  progress  has  been 
made in reducing non-human primate use, by, for example the development and validation of 
new methods for vaccine testing e.g. polio vaccine.  

Responses indicated that although some progress has been made, there are still areas where 
the  use  of  non-human  primates  remains  necessary.  The  main  areas  identified  were  in 
regulatory safety testing, neuroscience and certain infectious and neurodegenerative diseases.   

100 

 
 
 
 
 
Member State responses 

Use  of  NHPs  Has  the  use  of  non-human  primates  increased  or  decreased  under  the  new 
Directive? 

Increased 
No change 
Decreased 
Not applicable 

 1/28 
 11/28 
 2/28 
15/28 

Has there been any use of endangered non-human primates under the new Directive? 

No  
Yes 

 28/28 
-/28 

User responses 

Can  you  provide  any  specific  examples  of  areas  where  the  use  of  non-human  primates  has 
been replaced by non-animal methods or by other species? What were the reasons for these 
changes? Was the choice of species influenced by the project evaluation process required by 
the Directive? 

Examples of the responses included 

  “The  lab  currently  using  NHPs  is  now  also  developing  and  evaluating  imaging 

studies in humans as a replacement.” 

  “In  our  institution  we  investigate  the  complexity  of  memory  consolidation  and 

networks in the brain. This can seldom be replaced with alternative methods.”   

  “In non-preclinical experiments, NHP are replaced as much as we can by pigs. The 
choice of the pig was not influents by the process required by the directive, because 
this is our own consideration since a long time.”  

  “In terms of interspecies in-vitro metabolism, when two non-rodent species are closer 
to  humans,  the  primate  is  not  selected  for  toxicological  investigations.  The  minipig 
has been added to the list of non-rodent species to be tested in-vitro in order to select 
it for further in vivo experiments if required. The reasons behind this choice were not 
influenced by the project evaluation process, but more by ethical considerations and 
ease of implementation.” 

  “A  small  a  number  of  transgenic  mouse  models  have  been  developed  for  candidate 

selection and regulatory toxicology.” 

 

 “The  use  of  non-human  primates  cannot  be  replaced  by  non-animal  methods  in 
cognitive neuroscience.” 

101 

 
 
 
 
 
 
 
  "Most if not all our activities are based on regulatory requirements (ICH guidelines) 
and no change has observed with the new Directive. Whenever non-human primates 
are  necessary  for  scientific  purposes  (biological  target  or  metabolism  specificities), 
they are still used in the same way. More scrutiny is applied during project evaluation 
for the species selection." 

  "NHP  are  used  only  when  no  other  species  are  usable  (justification  based  on 
metabolism  data,  pharmacological  data,  toxicological  response  which  showed  that 
other species are not enough close to Human response). In some cases, in regulatory 
toxicity  development,  NHP  only  is  acceptable  by  the  authorities.  The  use  of  not 
adequate species doesn't allow to be in accordance with regulatory requirements" 

  "Non-human primates are  mainly used  to assess the safety of  biotechnology  derived 
drugs.  No  alternative  currently  exist  to  comply  with  international  regulatory 
guidelines (ie ICH) asking data from the "most predictive animal species" 

  “Use  of  NHPs  is  driven  by  complex  questions  of  vaccine  and  therapeutic  efficacy: 
thus animals are only used where there are no alternatives.  We have for many years 
developed and refined in vitro methods such as continuous culture that serve as early 
screening models for bacterial latency and potential antibiotic treatments.  However 
there is still a need to test novel therapies and vaccines in a relevant disease model 
prior to clinical trials. Choice of species is influenced by prior knowledge “  

  “NHP's were used in neurophysiology research for many years and these studies are 
stepwise  being  replaced  by  studies  in  rodents.  This  change  had  started  before  the 
implementation of the directive.” 

  “NHPs  are  only  used  in  the  absence  of  feasible  alternatives,  and  sparsely.  In  our 
institute,  this  is  restricted  to  the  use  for  research  on  infectious  diseases  that  are  a 
threat to public health, including emerging diseases.” 

Recommendations  

Member States  

  Continue  efforts  to  ensure  promotion  and  sharing  of  alternative  approaches  and 

dissemination of information at national level.  

  Develop a high-level strategy to encourage a shift of attitudes and priorities to make 

significant progress towards the implementation of non-animal methods. 

  Ensure training remains current in the field of alternatives and in the tools available to 

search for them. 

  Ensure that appropriate consideration is given to the use of alternatives in particular in 
the field of education, and that project evaluators are up-to-date in the advancement of 
alternatives in this field. 

102 

 
 
 
Users  

  Always  consider  alternative  methods  and  approaches,  including  thinking  laterally  to 

revise original hypotheses to try to replace animal use.  

  Ensure robust searches are carried out using all available, up-to-date resources to find 
potential alternatives in their field including in education and training. Demonstrate in 
the project applications why alternative methods available in the field will not suffice 
to fulfil the scientific objectives. 

Organisations with specific interest in alternatives 

  Develop  online  courses  in  alternative  methods  for  specific  areas  of  science, 

toxicology, and education and training. 

  Develop search tools for alternatives, especially in the non-regulatory use of animals. 

  In  existing  and  new  databases,  alternatives  should  be  accessible  by  discipline  e.g. 

neuroscience; immunology etc. 

  Develop  improved  communication  and  cooperation  among  relevant  "alternative 
stakeholders"  on  the  availability  and  the  potential  for  sharing  relevant  high-quality 
teaching resources at costs which could be acceptable to trainers / trainees.  

Training providers 

  Ensure,  in  cooperation  with  alternatives  organisations,  that  training  for  scientists 
importance  of  experimental  design  and 

the 

remains  current  and  prioritises 
implementation of the Three Rs. 

Regulatory authorities 

  Regulatory  agencies,  in  collaboration  with  Member  State  authorities  and  the  user 
community, should consider how the dissemination of information on newly adopted 
alternative  methods  could  be  improved  to  reach  all  relevant  players  in  a  timely 
fashion.  

2.9  DEVELOPMENT,  VALIDATION  AND  REGULATORY  ACCEPTANCE  OF 
NEW ALTERNATIVE APPROACHES 

The Directive provides obligations to both the European Commission and Member States to 
contribute to the development and validation of alternatives asset out in Article 47. However, 
the  type  and  nature  of  these  contributions  are  not  detailed  in  the  Directive.  Even  if  the 
validation or regulatory acceptance processes in different sectors are not in the direct remit of 
the  Directive,  it  provides  some  general  tools  and  infrastructures  aimed  at  facilitating  and 
accelerating  the  development,  validation  and  promotion  of  alternatives.  Furthermore,  it 

103 

 
 
 
requires  the  Member  States  to  promote  alternatives  at  national  level,  whilst  the  European 
Commission is required to promote acceptance and uptake at international level. 

More  precisely,  Article  47  requires  Member  States  to  appoint  laboratories  for  carrying  out 
validation studies (European Union Network of Laboratories for the Validation of Alternative 
Methods - EU-NETVAL) and to nominate a single point of contact to provide advice on the 
regulatory  relevance  and  suitability  of  new  alternative  approaches  proposed  for  validation 
(Preliminary Assessment of Regulatory Relevance PARERE Network).  

Article 48 created a legal basis for the European Union Reference Laboratory for Alternatives 
to  Animal  Testing  (EURL  ECVAM),  which  coordinates  the  validation  of  alternative 
approaches for both regulatory testing and basic and applied research.  

Animal  protection  organisations  stated  frustration  at  the  lack  of  funding  and  slow  progress 
towards validation and acceptance of alternative methods. However, responses indicated that 
there had been investment and activities to move this field forwards. 

There  were  requests  by  the  users  that  EURL  ECVAM  continue  to  broaden  the  remit  from 
predominantly regulatory toxicology area to be more balanced across other science areas.  

Structures and Processes Developed 

The  EURL  ECVAM  report  (in  Annex  2)  describes  the  structures  underlying  the  enlarged 
scope  of  EURL  ECVAM.  EU-NETVAL  was  set  up  as  a  laboratory  network  to  support 
validation  studies.  Article  47(5)  required  a  single  point  of  contact  to  provide  advice  on  the 
regulatory  relevance  and  sustainability  of  alternative  approaches  proposed  for  validation. 
This  network,  the  Preliminary  Assessment  of  REgulatory  Relevance  (PARERE),  is 
comprised of regulators nominated by Member States and representatives from EU regulatory 
agencies,  with  the  aim  of  expediting  regulatory  acceptance  of  alternative  methods.  In  line 
with  Annex  VII(e)  the  ECVAM  Stakeholder  Forum  (ESTAF)  was  established  to  maintain 
dialogue  with  industrial  and  research  organisations  and  society  as  a  whole,  with  outcomes 
released  on  the  EURL  ECVAM  website.  Scientific  expertise  is  provided  by  the  ECVAM 
Scientific  Advisory  Committee  (ESAC),  which  provides  independent  peer  reviews  of 
validation studies.  

The  work  of  these  networks  is  crucial  to  facilitate  smooth  progress  from  initial  method 
development, through validation into regulatory uptake. The networks have started to provide 
new  resources,  improve  coordination  of  tasks,  and  dissemination  of  information  on  new 
upcoming  alternative  approaches.  However,  especially  in  the  case  of  EU-NETVAL,  the 
current  work  is  somewhat  hindered  by  limited  funding  available  for  its  members.  Some 
Member  States  have  provided  specific  funds  for  these  activities  and  see  this  as  one  of  the 
practical ways to respond to Article 47(1) requirement to contribute to the development and 
validation of alternative approaches, however, this is not yet common practice. It is still very 
early days to draw even preliminary conclusions as to their actual impact in these processes. 

Research funding through EU research programmes 

104 

 
 
 
The  European  Commission  has  actively  supported  research  on  all  aspects  of  the  Three  Rs 
through its successive Framework Programmes for Research and Innovation (FPs), including 
the  current  seven-year  programme  Horizon  2020  (H2020:  2014  to  2020).  During  the  last 
decade, the European Commission funding in this field of research has remained stable and 
significant.  During  the  period  2012-2016,  sixty-nine  research  projects  were  running  at 
various  stages  of  implementation,  with  EUR  350  million  from  the  European  Commission 
programmes. These research projects have focussed mainly on alternatives to animals. They 
included  innovative  tools  for  safety  testing  of  chemicals,  nanomaterials  and  food  mixtures, 
quality  control  of  vaccines,  the  creation  of  databases,  tissue  cultures  with  human  induced 
pluripotent stem cells, bioinformatics and modelling. As part of this effort, thirteen projects 
were  co-financed  within  the  context  of  public-private  partnerships  with  Cosmetics  Europe 
(the  seven  projects  from  the  SEURAT-125  cluster)  or  the  European  Federation  of 
Pharmaceutical Industries and Associations (the six projects from the Innovative Medicines 
Initiative:  IMI26).  The  additional  resources  provided  by  the  industry  to  these  projects  were 
estimated to represent more than EUR 100 million. Overall, these projects developed a range 
of various novel in silico and in vitro approaches, from innovative modelling tools to multiple 
organs-on-a-chip, which could allow a significant replacement and reduction of test animals 
in biomedical sciences and safety testing.  

There is always a lag in the regulatory implementation of new alternative methods developed 
by any research  project, including projects with the European Commission  funding. This is 
usually  due  to  the  long  time  needed  between  the  development  of  the  methods,  their 
validation, and their regulatory acceptance. Therefore, regulatory impact starts to be observed 
from  FP627  (2002-2006)  projects  for  less  complex  toxicological  endpoints,  such  as  skin 
sensitization  for  instance.  Additional  regulatory  impacts  are  expected  to  come  out  of  FP728 
(2007-2013)  and  H202029  (2014-2020)  projects,  including  in  the  areas  of  more  complex 
toxicological  endpoints,  such  as  repeated  dose  systemic  toxicity,  developmental  and 
reproductive toxicity, and carcinogenesis. 

Progress on Alternatives 

Summarising from the EURL ECVAM report, significant progress has been made in the EU 
on alternatives since 2010. New amendments to Annexes of EC Regulation 1907/2006 on the 
Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH)30  have been 
made  regarding  skin  corrosion/irritation,  eye  irritation,  and  skin  sensitisation.  At  the 
International Conference on Harmonisation (ICH31) an in vitro test on phototoxicity has been 
included in ICH S10. Strategies have been developed in areas of acute mammalian systemic 
towards 
toxicity,  genotoxicity,  bioavailability,  endocrine  disruption, 

including  work 

25 http://www.seurat-1.eu/ 
26 http://www.imi.europa.eu/ 
27 https://ec.europa.eu/research/fp6/index_en.cfm 
28 https://ec.europa.eu/research/fp7/index_en.cfm 
29 https://ec.europa.eu/programmes/horizon2020/ 
30 OJ L 396, 30.12.2006, p. 1 
31 http://www.ich.org/home.html 

105 

 
 
 
                                                            
Integrated Approaches to Testing and Assessment (IATA) in some of these areas. Addition to 
OECD32  Guideline 236  (zebrafish  embryo  acute  toxicity  test)  and  Guidance  Document  126 
(Short guidance on the use of the threshold approach for acute fish toxicity testing) have been 
progressed to work towards replacement of acute fish testing. ECHA33 have concluded that 
OECD Guideline 236 can be used in a weight of evidence approach. 

There has also been significant progress in the quality control of pharmaceuticals, including 
an agreement to delete the general safety test/abnormal toxicity test from batch safety testing, 
since more adequate quality control measures are in place. 

As described in the SCHEER Opinion on the use of non-human primates, progress has been 
made  in  replacement  strategies  for  treatment  and  prevention  of  infectious  diseases with  the 
development  and  use  of  controlled  human  challenge  models  for  typhoid,  Plasmodium 
falciparum  malaria  and  transmission  studies  with  specific  influenza  strains,  and  in  the 
development and safety testing of new medicines. Furthermore, non-human primates are no 
longer considered acceptable organ donors for practical and ethical reasons. 

SCHEER Opinion, however, underlined that where alternatives do not exist, appropriate use 
of non-human primates remains essential in some areas of biomedical and biological research 
and for the safety assessment of pharmaceuticals.  

Due  to  a  wide  number  of  factors  influencing  the  speed  of  progress  in  obtaining  new 
alternative approaches to replace the use of non-human primates, it is currently not feasible to 
set up a timeline to phase out their use. A number of the recommendations contained in the 
SCHEER  Opinion  have  been  incorporated  in  this  review  report.  However,  as  these  are 
applicable  beyond  non-human  primate  use,  these  have  been  worded  to  give  more  general 
applicability. 

In the light of the general progress made with alternatives, the indications are that the revised 
framework and structures within the Directive support the delivery of the policy objectives, 
and that the provisions contained in it remain fully valid. 

Member  State  contribution  to  the  development  and  validation  of  alternatives 
approaches  

As  stated,  the  Directive  requires  that  the  Member  States  contribute to  the  development  and 
validation  of  alternative  approaches.  14  out  of  28  Member  States  have  submitted  voluntary 
reports34  under  Article  47  detailing  the  approaches  taken  to  the  efforts  made  towards  the 
development, validation and promotion of alternative methods.  

Many  Member  States  have  increased  their  activities,  for  example,  increasing  research 
funding,  development  of  Three  Rs  centres,  supporting  educational  seminars/workshops, 
publishing  links  to  information  on  the  Three  Rs,  and  contributing  to  EU-NETVAL  and 
PARERE networks, and EURL ECVAM activities..  

32 http://www.oecd.org/chemicalsafety/testing/oecd-guidelines-testing-chemicals-related-documents.htm 
33 https://echa.europa.eu/ 
34 http://ec.europa.eu/environment/chemicals/lab_animals/3r/advance_en.htm 

106 

 
 
 
                                                            
Although  it  is  still  premature  to  assess  the  impact,  increased  activity  in  this  area  has  been 
confirmed.  In  many  Member  States,  there  is  an  increased  political  awareness  of  the 
importance of the Three Rs. Examples of how Three Rs are promoted by the Member States 
include: 

  At  national  level,  requiring  and  ensuring  biostatistical  input  at  AWB  and  project 

evaluation process; 

  Annual  meetings  and  training  events  with  the  scientific  community  to  promote  the 

Three Rs; 

  Examples of specific work to eliminate certain animal use e.g. shellfish bioassay; 
  Educational programmes promoting alternatives in non-EU countries; 
  Establishment of national Three Rs centres. 

In  conclusion,  despite  being  still  in  the  early  stages  after  implementation  of  the  Directive, 
there  has  been  increased  attention  given  by  Member  States  and  users  towards  progressing 
alternatives. However, it is evident that there is still some way to go to improve the access to 
and  dissemination  of 
increase  Member  State 
information  on  existing  alternatives, 
contributions  to  the  development  and  validation  of  new  alternatives,  and  to  ensure 
comprehensive uptake by the scientific community. 

Recommendations  

  The Commission services should request regular updates to the SCHEER Opinion to 
closely monitor progress in the development and uptake of alternatives replacing the 
use of non-human primates. 

  Member States, where not yet done, should consider ways in which the activities of 

their respective EU-NETVAL laboratories could be better supported. 

SECTION 3 – IMPROVING TRANSPARENCY  

Transparency is essential to develop a trust in the systems of ethical and socially acceptable 
care and use of animals in science as the basis for a continued research using animals in the 
EU  until  such  time  their  use  can  be  replaced  by  non-animal  alternatives.  The  Directive 
introduced a number of elements aimed at improving transparency.  

The  majority  of  Member  States  and  users  were  of  the  view  that  the  requirements  in  the 
Directive for publication of non-technical project summaries and annual statistical data have 
positively contributed to transparency, although the full impact has yet to be realised. 

Among the scientific stakeholder responses, there was a similar response, but around 40% of 
the animal protection organisations disagreed or strongly disagreed that the Directive had yet 
improved transparency. The main concerns expressed regarded the accessibility and quality 
of  non-technical  project  summaries,  the  lack  of  detailed  statistics  in  the  new  format  from 
certain Member States, and the lack of transparency of the project evaluation process. 

107 

 
 
 
 
Two key areas of change regarding transparency are required by the Directive, the obligation 
on Member States to publish non-technical project summaries (Article 43) and more detailed 
annual  statistical 
information  (Article  54  and  Commission  Implementing  Decision 
2012/707/EU35)  on  the  use  of  animals  in  procedures,  including  information  on  the  actual 
severity  of  procedures  and  on  the  origin  and  species  of  non-human  primates  used  in 
procedures. Member States are also required to ensure that the project evaluation process is 
transparent (Article 38). 

Article  57  requires  that  the  Commission  shall  submit  an  implementation  report  and  a 
summary  report  of  the  statistical  information  provided  by  Member  States  by  10  November 
2019. 

The Directive furthermore requires in Article 38(4), that the project evaluation is performed 
in  an  impartial  manner  and  the  process  needs  to  be  transparent.  Finally,  inspections  under 
Article 34 will play an increasing role in improving transparency and public accountability in 
all use and care of animals for scientific purposes. 

User responses 

The  Directive  has  improved  the  transparency  of  animal  use  for  scientific  purposes  in  my 
country/region? 

Users 

The  majority  of  users  agreed  that  the  requirements  in  the  Directive  for  publishing  non-
technical  project  summaries  and  reporting  statistical  information,  including  on  severity  of 
procedures  experienced  by  the  animals,  have  improved  transparency.  However,  these 
publications  are  reported  not  always  to  be  easily  found,  and  the  content  can  be  quite/too 
technical.  

35 http://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:02012D0707-20140115&from=EN 

108 

 
 
 
 
 
                                                            
The  Directive  is  one  factor  among  a  number  of  initiatives  to  improve  understanding  of  the 
use of animals in research to general public.  

Comments 

  "It  is  important  to  explain  the  importance  of  laboratory  animals  in  research. 
Explanation and transparency are critical for a better understanding of this research 
in Europe." 

  "Organisations  such  as  Understanding  Animal  Research  (UAR)  and  European 
Animal  Research  Association  (EARA)  are  making  significant  progress  in  this  area 
and  have  been  widely  supported  by  the  scientific  community  eg  Concordat  on 
Openness." 

The  majority  of  Member  States  and  users  were  of  the  view  that  the  requirements  in  the 
Directive  for  publication  of  non-technical  project  summaries  and  annual  statistics  have 
positively contributed to transparency, although the full impact has yet to be realised. 

109 

 
 
 
 
 
Stakeholder responses 

All stakeholders 

Other stakeholder organisations 

Animal protection organisations 

Just  under  half  of  the  stakeholder  organisations  (25)  agree  that  the  Directive  has  had  a 
positive  effect, 11 disagree with  this view.  While nine of the animal protection stakeholder 
organisations  agree  that  the  Directive  has  improved  the  transparency  of  animal  use,  eight 
others either disagree or strongly disagree with this view. 

Greater transparency is requested, in particular with the detail and balance of non-technical 
project  summaries.  Few  Member  States  seem  yet  to  have  published  the  process  of  project 
evaluation.  

Many animal protection organisations expressed concerns over the lack of transparency in the 
new processes introduced under the Directive, and over the quality of non-technical project 
summaries and inadequacies in the annual statistical reporting by some Member States. 

Two Member States make public the majority of the content of authorised projects (excluding 
personal  information  and  Intellectual  Property)  and  a  number  of  animal  protection 
organisations request improved access to the details of projects.    

The scientific community need to continue and improve efforts to explain why at this stage 
the use of animals in scientific procedures is still necessary, and what efforts are being made 
to replace animal use.  

110 

 
 
 
 
 
 
 
111 

 
 
 
 
 
Accessibility 

Collecting  statistical  data  and  publishing  non-technical  project  summaries  will  improve 
transparency  only  if  the  information  is  readily  accessible.  Accessibility  of  information 
appears  from  many  users'  and  science  stakeholders’  comments  to  require  further  attention. 
Respondents pointed out that accessibility comprises of at least two issues – to know where 
to find information and to know how to interpret the data. Until these are addressed there is 
scope for improvement to truly increase transparency. 

3.1 NON-TECHNICAL PROJECT SUMMARIES (ARTICLE 43) 

Summary 

The non-technical project summaries are considered a key tool to improve transparency in the 
area  of  the  use  of  animals  for  scientific  purposes.  Article  43  of  the  Directive  calls  for 
information  on  the  objectives  and  benefits  of  the  project,  numbers  and  types  of  animals 
(species and life-stages) of animals to be used, and the predicted harms to the animals which 
are expected to occur as a result of the procedures applied. It is also necessary that the non-
technical project summaries include information on compliance with the Three Rs. 

Non-technical  project  summaries  were  published  by  two  Member  States  already  before  the 
new  Directive.  Six  have  not  yet  managed  to  publish  them,  but  over  half  of  Member  States 
agree that there has been an increase in transparency as a result of publication. More than half 
of  scientific  users  felt  that  transparency  had  improved  as  a  result  of  publication  of  non-
technical project summaries, a view agreed by most scientific stakeholders.  

Significant differences in quality have been noted by animal protection groups. In particular, 
concerns  were  raised  about  a  lack  of  appropriate  balance;  emphasising  generic,  sometimes 
unrealistic benefits without sufficient information on harms. The views expressed were that 
authorities should ensure accuracy and balance of published non-technical project summaries. 
Non-technical project summaries should be timely, easily accessible and searchable which is 
not  yet  the  case  in  many  Member  States.  The  development  of  a  central  EU  database,  with 
open  access  and  search  facilities,  was  highlighted  as  a  potential  tool  to  provide  a  pan-
European view of the scientific use of animals. 

Member State responses 

Has  the  publication  of  Non-technical  Project  Summaries  improved  transparency  in  your 
Member State? 

Yes 
No 
No opinion 
Too early to assess 

 17/28 
 1/28 
 6/28 
4/28 

112 

 
 
 
 
The  timing  of  publication  after  project  authorisation  varies  considerably,  from  immediately 
post-authorisation  to  30  months.  Eight  Member  States  publish  within  six  months  of 
authorisation. 

A  recommendation  for  a  format  for  presentation  and  content  of  non-technical  project 
summaries  was  agreed  at  a  National  Contact  Point  meeting  and  has  been  adopted  by  a 
number  of  Member  States.  The  Directive  leaves  it  to  the Member  States  to  decide  whether 
non-technical  project  summaries  should  be  updated  with  the  results  of  retrospective 
assessment of projects. Not all Member States have opted to provide this update. 

User responses 

  "Non-technical  project  summaries  facilitate  the  understanding  for  and  increase  the 
availability of facts for the general public and policy makers, and are now published 
(or will be) by all countries." 

  "There is more discussion internally within an establishment." 

  "Difficult  to  find  the  non-technical  summaries  and  statistics  makes  us  think  that 

transparency is not optimal." 

  "The Directive has improved the level of information which is available to the public, 
for  example on actual  severity. With regards to NTS the public can see the types of 
projects  approved,  however,  due  to  confidentiality  issues  there  is  little  detail  on  the 
benefits."  

  "The  non-technical  project  summaries  include  the  danger  that  information  becomes 
state of the art which leaves "burnt ground" for intellectual property protection." 

  "The NTS's did not really improve the transparency to the general public (except for 
activists).  Our  institute  is  working  together  with  European  Animal  Research 
Association  (EARA)  to  improve  transparency.  It  is  up  to  each  institute  to  ensure 
transparency of the research." 

In addition, some said that there was not  much information  in  the non-technical project 
summaries. 

Stakeholder responses 

Publication times should be improved and the project evaluation process should ensure that 
the non-technical project summary is an accurate representation of the project. 

Comments 

  "Non-technical  summaries  are  too  often  poorly  (and  too  technically)  written,  one-

sided and give minimal insight." 

113 

 
 
 
  "There are significant shortcomings in the quality and tone of the NTSs." 

  "The  NTSs  are  written  by  the  scientists  without  any  “neutral”  editing,  thus  animal 
suffering is often downgraded, while the alleged benefits are exaggerated. The NTSs 
should  be  provided  by  the  authorities  and  include  details  of  the  harm-benefit 
analysis." 

  "Many  read  like  PR  documents,  extolling  alleged  benefits  and  downplaying  or 

ignoring suffering." 

  "Harms  to  animals  are  not  described  detailed  enough  in  common  language  that 

people could have a change to judge the nature of the experiment." 

Recommendations  

  Training  for  scientists  (EU  Education  and  Training  Framework  Module  11)  should 
include training on requirements and expectations of non-technical project summaries. 

  Member States should ensure that non-technical project summaries are published in a 

timely manner. 

  Competent  authorities,  through  the  project  evaluation  and  authorisation  processes, 
should  ensure  that  non-technical  project  summaries  are  accurate,  fairly  represent 
harms  and  be  realistic  about  the  expected  benefits  to  improve  the  quality  of  non-
technical project summaries. 

  The  Commission  services,  Member  States  and  stakeholders  should  explore 
possibilities of a central repository of (or provide easy, searchable access to) all non-
technical  project  summaries  at  EU  level  taking  into  account  the  legal  requirements 
and linguistic limitations.  

3.2 STATISTICAL DATA (ARTICLE 54) 

Statistical  reporting  was  comprehensively  revised  after  the  adoption  of  the  new  Directive. 
The  reporting  requirements  are  detailed  in  the  Commission  Implementing  Decisions 
2012/70/EU. Member States were required to publish statistical data on the basis of the new 
requirements  for  the  first  time  in  2015.  Although,  all  Member  States  have  published  their 
national  data,  most  did  not  include all  the  new data elements  as  set  out  in  the  Commission 
Implementing Decision. 

It  is  too  early  to  determine  the  impact  of  the  new  reporting  requirements  on  improving 
transparency,  but  for  the  first  time  in  EU  information  is  provided  inter  alia  on  the  actual 
severity experienced by each animal used. The origin and species of non-human primates is 
also reported. Further work is necessary by all involved to ensure coherent reporting across 
the EU in time for the first EU report in 2019, and every three years thereafter.  

114 

 
 
 
The  scientific  community  needs  to  continue  and  improve  efforts  to  explain  to  wider 
audiences why, at this stage, the use of animals in scientific procedures is still necessary, and 
what efforts are being made to replace animal use. Statistical reports need to be explained and 
contextualised  to  improve  communication  with  the  public  about  what  these  numbers  and 
categories  mean.  The  importance  of  consistent  and  understandable  terminology  was 
highlighted. 

115 

 
 
 
 
 
Member State responses 

Is  the  new  information  collected  under  Commission  Implementing  Decision  2012/707/EU 
helpful  in  presenting  improved  data  on  animal  use  to  the  general  public  in  your  Member 
State? 

Yes 
No 
No opinion 
Too early to assess 

 19/28 
 1/28 
 2/28 
6/28 

The  reporting  system  has  been  very  helpful,  but  it  has  been  challenging  to  ensure  that  all 
users understand and implement the changed requirements, for example reporting animals at 
the end of procedure and reporting actual severity for each animal. 

User responses 

  Some pointed out that changes in reporting, leading to changes (particularly increases) 
in  numbers  of  animals  used  need  to  be  clearly  explained  during  the  publication 
process,  especially  if  this  is  not  actually  an  increase  but  just  a  change  in  the  way 
reporting occurs. 

  Some said that the accessibility (know where to find it and know how to interpret the 
data) of the information needs to be addressed before it can be said to be an increase 
in transparency. 

  "The average person has no idea about what genetic status, categories and (assumed) 

severities means."  

Stakeholder responses 

  "Statistical  reports  need 

to  be  explained  and  contextualised 

to 

improve 

communication with the public." 

Recommendations  

  Member  States,  when  publishing  statistical  data,  as  set  out  in  the  Commission 
Implementing  Decision  2012/707/EU,  should  use  the  accompanying  narrative  to 
communicate  about  animal  use  in  the  wider  context  and  explain  key  findings  and 
trends in a manner that is easily understood by the general public. 

3.3 PROJECT EVALUATION (ARTICLES 36 AND 38) 

In Article 38(4), the Directive requires that the project evaluation is performed in an impartial 
manner and the process needs to be transparent. Specific guidance has been produced at EU 

116 

 
 
 
 
level  to  assist  in  the  development  of  these  processes36.  There  was  a  high  awareness  of  the 
guidance within the user community, although availability, including in some languages has 
been  reported  to  be  an  issue  for  developing  efficient  and  effective  processes,  and  would 
consequently  be  a  hindrance  to  transparency  at  the  time  of  the  consultation37.  The  greater 
majority  of  Member  States  have  disseminated  the  EU  Guidance  on  project  evaluations, 
although some only recently.  

Some Member States have published their processes and the related requirements for project 
evaluation  and  authorisation,  and  shared  their  information  as  part  of  this  consultation  but 
these are not yet universally available throughout EU. It is not clear in many cases whether 
these processes have been communicated only to project evaluators, or whether they are more 
widely  available  to  other  stakeholders,  which  would  improve  the  transparency  of  the 
Directive expectations. Animal protection organisations requested improved transparency on 
the processes used in project evaluation and authorisation. This would provide greater public 
confidence that the Three Rs are being applied. 

The  National  Committee  should  have  a  role  in  ensuring  a  harmonised  approach  to  project 
evaluation by different competent authorities (when more than one) throughout the country. It 
would be likely that this would include a described transparent approach to project evaluation 
including  harm-benefit  assessment.  Only  seven  National  Committees  had  done  this  at  the 
time  of  the  consultation.  Users  in  many  Member  States  requested  clarification  of 
requirements for project evaluation to improve efficiency of the process. 

Mutual  acceptance  of  project  evaluations  was  requested  by  some  users  and  scientific 
stakeholders  to  facilitate  transfer  of  projects  or  collaborative  multi-site  projects  involving 
more than one Member State. If such processes are published and accessible, this might assist 
in  determining  whether  a  country’s  process  complied  with  the  requirements  of  another 
Member State.  

Just  over  half  of  the  Member  States  stated  that  the  Guidance  on  project  evaluation    and 
retrospective assessment was helpful, and several had used it to develop processes applicable 
within their own Member State. Few if any comments from users directly related to project 
evaluation Guidance, but there was clearly some scope for improvement of dissemination of 
individual Member State processes to the scientific community. The Guidance document on 
Severity  Classification  is  also  widely  used  in  project  evaluation,  although  further  examples 
of, in particular, studies using genetically altered animals have been requested by some users 
and  Member  States  to  assist  in  the  transparency  and  consistency  of  decision-making  on 
assignment  of  severity.  Some  Member  States,  and  stakeholder  organisations  are  already 
developing these. 

Some Member States and users requested more information on the availability of the Three 
Rs and it is not clear whether they were aware of the Working Document on the Availability 
of Information on the Three Rs.  

36 http://ec.europa.eu/environment/chemicals/lab_animals/pdf/Endorsed_PE-RA.pdf  
37 Guidance in all community languages became available during the consultation period in June 2016  

117 

 
 
 
                                                            
Recommendations  

  Member States should publish easily accessible, transparent requirements for project 
evaluation, the related operational processes and responsibilities, and provide clarity 
on  the  criteria  for  the  type  of  omissions  that  result  in  rendering  an  application 
incomplete/incorrect, and how these are processed (including timelines). 

3.4 INSPECTIONS (ARTICLE 34) 

Requirements for inspections are detailed in Article 34.  Details of inspections, including the 
proportion of announced and unannounced visits, and details of non-compliance form part of 
Member State implementation reports due in  2018, consequently insufficient information is 
available  yet  for  a  comprehensive  analysis.  When  available,  these  will  increase  the 
transparency of the inspection process.  

In  half  of  the  Member  States  there  has  been  no  change  in  inspection  frequency,  with  13 
Member States indicating an increase. The majority of users have not yet noticed any change 
in inspection frequency, but almost a third have reported an increase.  

The EU guidance38 has generally been found to be helpful, and the common EU risk criteria 
are  being  used  by  the  majority  of  Member  States.  A  number  of  Member  States  have 
developed  additional  guidance  to  assist  inspectors.  Some  Member  States  reported  specific 
training  initiatives  directed  to  inspectors,  a  practice  that  would  benefit  from  a  wider 
implementation,  especially  in  countries  where  inspections  under  this  Directive  form  only  a 
minor part of the role of the inspectors.   

SECTION 4 - ADDITIONAL COMMENTS 

During  the  consultation  process,  stakeholders  were  invited  to  provide  additional  comments 
relevant  to  the  review  of  the  Directive.  Below  is  a  summary  of  the  main  comments,  not 
discussed elsewhere in the Staff Working Document. 

Member State comments 

16  Member  States  provided  additional  comments.  Among  the  issues  raised  by  individual 
Member States included request for clarification over the upper limit of pain and suffering, 
and concerns over procedures causing intense/severe pain and suffering.  

User comments 

  "A much more supporting attitude is necessary by some authorities, as it is perceived 
that otherwise “this important sector of research in life sciences will be deteriorating 
in Europe completely”." 

38 http://ec.europa.eu/environment/chemicals/lab_animals/pdf/guidance/inspections/en.pdf 

118 

 
 
 
 
 
                                                            
  "Improve  communication  between  institutions,  and  between  regulators  and  users 

(direct not indirect via others)" 

  "The Directive has necessitated closure of some animal units as they did not comply 
with the requirements, but it has helped in the design of the replacement facilities."  

  "It  is  especially  important  that  a  central  part  of  the  Directive  is  the  case-by-case 
evaluation  of  projects.  In  our  opinion,  this  is  the  only  way  to  deal  with  a  complex, 
ethically  challenging  topic  such  as  animal  experiments.  The  benefit  to  humans 
through the further development of science and the welfare of animals are both very 
important  goals,  and  balancing  them  in  a  responsible  manner  will  not  be  achieved 
through blanket assessments. Therefore the principle to have each individual project 
evaluated is the only way of doing the difficulty of the issue justice. The Directive is 
doing just that, providing a good balance between the goals of scientific progress and 
animal welfare.” 

Stakeholder comments 

Animal protection stakeholder comments 

Some  animal  protection  organisations  provided  additional  contributions,  which  have  been 
considered and incorporated as applicable in the relevant sections of this document.  

Some elements put forward concerned issues that are outside the scope of this Directive such 
as processes for regulatory acceptance of (alternative) test methods detailed in different sector 
legislation e.g. for chemicals or pharmaceuticals.  

A  number  of  contributions  called  for  the  use  of  thematic  reviews,  especially  on  the  use  of 
non-human primates and alternatives.  

Other comments included: 

  "Further  improve  transparency  with  publication  of  Projects  and  Retrospective 

Assessments." 

  "Require robust, effective enforcement by well-trained Inspectors."  

  "There  needs  to  be  stronger  enforcement  of  regulation  to  use  alternatives  and 
infrastructure put in place to ensure that non-animal method developments are more 
widely disseminated." 

Other stakeholder comments 

  “For  scientists  in  many  MS,  there  have  not  been  significant  changes  to  the 

requirements”.   

119 

 
 
 
 
  "Acknowledgement that use of animals will be necessary for the foreseeable future – 

there will not be alternatives to address every scientific question or need." 

  "The  industry  expected  a  level  playing  field  with  no  gold  plating  of  standards.  It  is 
important  that  the  Directive  is  fully  implemented  by  all  EU  members  as  quickly  as 
possible and policed properly going forward to ensure that this happens."  

  "The  positives  impact  includes  raising  standards  in  research  practice,  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. Much is subjective and it would be useful if the EC could think about 
how  funding  might  be  directed  towards  building  a  stronger  evidence  base  in  this 
area" 

  "To achieve the goals, the EC has to react quickly and firmly against countries that 
do  not  implement  the  basics  of  the  Directive,  as  this  will  create  imbalances  for 
research  within  the  union  and  confusion  in  public  opinion  as  standards  in  different 
MS will differ so much." 

120 

 
 
 
 
LIST OF ABBREVIATIONS 

AFSTAL - l'Association Française des Sciences et Techniques de l'Animal de Laboratoire 

AWB   - Animal Welfare Body 

CA 

- Competent Authority 

CPD 

- continued professional development 

CRO   - contract research organisation 

DB-ALM - Database on Alternative Methods 

DV 

- Designated Veterinarian 

EARA - European Animal Research Association 

EU  

- European Union 

EC  

- European Commission 

ECHA - European Chemicals Agency 

EMA  - European Medicines Agency 

ESAC - EURL ECVAM Scientific Advisory Committee 

ESTAF - EURL ECVAM Stakeholder Forum 

ETPLAS - Education and Training Platform in Laboratory Animal Science 

EURL ECVAM - EU Reference Laboratory for  
              Alternatives to Animal Testing 

EU-NETVAL - European Union Network of Laboratories for the Validation of Alternative  
              Methods 

E&T   - education and training 

FELASA - Federation for Laboratory Animal Science Associations 

GA 

- genetically altered 

IAT  

- Institute of Animal Technology 

IATA  - Integrated Approaches to Testing and Assessment 

ICH   - the International Council for Harmonisation of Technical Requirements for 
              Pharmaceuticals for Human Use 

IMI 

- Innovative Medicines Initiative 

LASA - Laboratory Animal Science Association 

121 

 
 
 
 
MS 

- Member State 

NC 

- National Committee 

NCP 

 - National Contact Point – Member State authority responsible for the implementation 
   of the Directive 

NC3Rs - National Centre for the Replacement, Refinement & Reduction of Animals in 
               Research 

NHP  - non-human primate 

NTS   - Non-technical Project Summary  

OECD - the Organisation for Economic Co-operation and Development 

PA 

- Project Authorisation 

PARERE - Preliminary Assessment of Regulatory Relevance Network  

PE 

- Project Evaluation 

RSPCA - Royal Society for the Prevention of Cruelty to Animals 

SCHEER - Scientific Committee on Health, Environmental and Emerging Risks 

TFEU - Treaty on the Functioning of the European Union 

TSAR - Tracking System for Alternative Test Methods 

UAR  - Understanding Animal Research 

UFAW - Universities Federation for Animal Welfare 

3R 

- Three Rs (Replacement, Reduction and Refinement of animal use and care) 

122 

 
 
 
 
 
 
ANNEXES 

1. List of recommendations 

2. Report by EURL ECVAM  

123 

 
 
 
 
 
 
 
ANNEX 1: LIST OF RECOMMENDATIONS 

1. HARMONISATION OF LEGISLATION 

1.1 Project evaluation 

1.  The  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". 

2.  Member 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.    

3.  Where 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. 

4.  Member  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. 

5.  Training  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. 

6.  Urgent  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  

7.  Further guidance should be developed to improve clarity on the minimum threshold of 

severity needed to bring a procedure under the scope of the Directive. 

8.  The  European  Commission  should  propose  amendments  to  Annexes  III  and  IV  for 

cephalopods once sufficient evidence is available. 

124 

 
 
 
 
9.  The 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 

10. Efforts 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. 

11. The  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. 

12. ETPLAS 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  

13. Member  States  should  provide  evidence-based  cases  to  the  Commission  services 

where amendments to Annexes III and IV are considered appropriate. 

14. With 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 

2.1 Animal Welfare Bodies 

15. Establishments  and  Member  States  (through  inspection)  should  ensure  that  all  core 

tasks of the AWB are being fulfilled. 

16. Member  States  should  clarify  roles  and  responsibilities  of  the  AWB  and  project 
evaluation,  in  particular  where  there  may  be  some  integration  or  overlap  with 
following  the  development  of  projects,  including  application  of  the  Three  Rs  and 
project evaluation process. 

17. Senior  management  of  the  establishment  should  ensure that  the  AWB  has  sufficient 

resources and empowerment to carry out the required tasks. 

18. Establishments  could  consider  the  addition  of  a  Designated  Veterinarian  as  a  full 

member of the AWB. 

125 

 
 
 
2.2 National Committees 

19. Member States should facilitate and resource National Committees where this is not 
yet established, or where it is not fully functional, to ensure that its role and tasks are 
fulfilled as these tasks play key roles in the attainment of the overall objectives of the 
Directive. 

20. In  preparation  for  the  EU  implementation  report  under  Article  57,  Member  States 

should look closer at whether and how National Committees are:  

o  facilitating a coherent approach to project evaluation within the Member State 

and 

o  exchanging good practice, including the promotion of Three Rs.  

2.3 Training and education and requirements for personnel 

21. Where  not  yet  available,  Member  States  should  publish  minimum  requirements  for 
education and training, and for obtaining, demonstrating and maintaining competence, 
and increase efforts to disseminate EU and other guidance on education and training 
to  scientific  users  to  indicate  their  expectations  for  trained  and  competent  staff. 
National  guidance  should  be  shared  with  the  relevant  stakeholder  organisations  and 
other Member States. 

22. Member  States  should  ensure  clarity  of  Article  24  roles,  in  particular  those  of  the 
training  and  information  persons,  to  ensure  effective  implementation  and  also  to 
increase  awareness  of  their  role  and  the  support  they  can  provide  within 
establishments. 

2.4 Reuse 

23. The Commission services and Member States should develop additional guidance on 

reuse.  

2.5 Avoidance of unnecessary duplication 

24. Member  States  should  re-enforce  the  awareness  of  the  need  for  researchers  and 
project evaluators to ensure that no unnecessary duplication takes place, in particular, 
in the development of new genetically altered animal lines. 

2.6 Setting free and rehoming 

25. Where  appropriate,  Member  States  should  share  relevant  guidance  material  on 
rehoming,  as  well  as  make  use  of  guidance  developed  by  other  Member 
States/stakeholder organisations.  

126 

 
 
 
2.8 Use of existing alternative approaches and implementation of the Three Rs 

Member States  

26. Continue  efforts  to  ensure  promotion  and  sharing  of  alternative  approaches  and 

dissemination of information at national level.  

27. Develop a high-level strategy to encourage a shift of attitudes and priorities to make 

significant progress towards the implementation of non-animal methods. 

28. Ensure training remains current in the field of alternatives and in the tools available to 

search for them. 

29. Ensure that appropriate consideration is given to the use of alternatives in particular in 
the field of education, and that project evaluators are up-to-date in the advancement of 
alternatives in this field. 

Users  

30. Always  consider  alternative  methods  and  approaches,  including  thinking  laterally  to 

revise original hypotheses to try to replace animal use.  

31. Ensure robust searches are carried out using all available, up-to-date resources to find 
potential alternatives in their field including in education and training. Demonstrate in 
the project applications why alternative methods available in the field will not suffice 
to fulfil the scientific objectives. 

Organisations with specific interest in alternatives 

32. Develop  online  courses  in  alternative  methods  for  specific  areas  of  science, 

toxicology, and education and training. 

33. Develop search tools for alternatives, especially in the non-regulatory use of animals. 

34. In  existing  and  new  databases,  alternatives  should  be  accessible  by  discipline  e.g. 

neuroscience; immunology etc. 

35. Develop  improved  communication  and  cooperation  among  relevant  "alternative 
stakeholders"  on  the  availability  and  the  potential  for  sharing  relevant  high-quality 
teaching resources at costs which could be acceptable to trainers / trainees.  

Training providers 

36. Ensure,  in  cooperation  with  alternatives  organisations,  that  training  for  scientists 
importance  of  experimental  design  and 

the 

remains  current  and  prioritises 
implementation of the Three Rs. 

127 

 
 
 
Regulatory authorities 

37. Regulatory  agencies,  in  collaboration  with  Member  State  authorities  and  the  user 
community, should consider how the dissemination of information on newly adopted 
alternative  methods  could  be  improved  to  reach  all  relevant  players  in  a  timely 
fashion.  

2.9 Development, validation and regulatory acceptance of new alternative 
approaches 

38. The Commission services should request regular updates to the SCHEER Opinion to 
closely monitor progress in the development and uptake of alternatives replacing the 
use of non-human primates. 

39. Member States, where not yet done, should consider ways in which the activities of 

their respective EU-NETVAL laboratories could be better supported. 

SECTION 3 – IMPROVING TRANSPARENCY  

3.1 Non-Technical Project Summaries 

40. Training  for  scientists  (EU  Education  and  Training  Framework  Module  11)  should 
include training on requirements and expectations of non-technical project summaries. 

41. Member States should ensure that non-technical project summaries are published in a 

timely manner. 

42. Competent  authorities,  through  the  project  evaluation  and  authorisation  processes, 
should  ensure  that  non-technical  project  summaries  are  accurate,  fairly  represent 
harms  and  be  realistic  about  the  expected  benefits  to  improve  the  quality  of  non-
technical project summaries. 

43. The  Commission  services,  Member  States  and  stakeholders  should  explore 
possibilities of a central repository of (or provide easy, searchable access to) all non-
technical  project  summaries  at  EU  level  taking  into  account  the  legal  requirements 
and linguistic limitations.  

3.2 Statistical data 

44. Member  States,  when  publishing  statistical  data,  as  set  out  in  the  Commission 
Implementing  Decision  2012/707/EU,  should  use  the  accompanying  narrative  to 
communicate  about  animal  use  in  the  wider  context  and  explain  key  findings  and 
trends in a manner that is easily understood by the general public. 

128 

 
 
 
3.3 Project Evaluation 

45. Member States should publish easily accessible, transparent requirements for project 
evaluation, the related operational processes and responsibilities, and provide clarity 
on  the  criteria  for  the  type  of  omissions  that  result  in  rendering  an  application 
incomplete/incorrect, and how these are processed (including timelines). 

129 

 
 
 
 
 
 
 
 
ANNEX 2: REPORT BY EURL ECVAM 

EURL ECVAM's contribution to the review of Directive 2010/63/EU on the protection of animals 
used for scientific purposes (status of 13/02/2017) 

Background 

Directive  2010/63/EU  formally  established 
Alternatives to Animal Testing (EURL ECVAM) and defined its duties in Article 48 and Annex VII. 

the  European  Union  Reference  Laboratory  for 

Its key responsibilities are to (a) coordinate and promote the development and use of alternatives to 
procedures  in  the  areas  of  basic  and  applied  research  and  regulatory  testing;  (b)  coordinate  the 
validation  of  alternative  approaches  at  Union  level;  (c)  act  as  a  focal  point  for  the  exchange  of 
information  on  the  development  of  alternative  approaches;  (d)  set  up,  maintain  and  manage  public 
databases and information systems on alternative approaches and their state of development, and; (e) 
promote dialogue between legislators, regulators, and all relevant stakeholders, in particular, industry, 
biomedical  scientists,  consumer  organisations  and  animal-welfare  groups,  with  a  view  to  the 
development,  validation,  regulatory  acceptance,  international  recognition,  and  application  of 
alternative approaches.  

The  directive  also  mentions  in  the  same  Annex  that  the  Union  Reference  Laboratory  should 
participate in the validation of alternative approaches.    

These duties are in line with the former Commission Communication to the Council and the European 
Parliament on the establishment of a European Centre for the Validation of Alternative Methods39.  

The Directive  mandates the application of scientifically valid alternative approaches and establishes 
mechanisms to speed up their development, validation and uptake. 

For example, Article 47 requires that "The Commission and the Member States shall contribute to the 
development and validation of alternative approaches which could provide the same or higher levels 
of  information  as  those  obtained  in  procedures  using  animals,  but  which  do  not  involve  the  use  of 
animals or use fewer animals or which entail less painful procedures, and they shall take such other 
steps as they consider appropriate to encourage research in this field." This provision is known as the 
"Three  Rs40",  i.e.  replacement,  reduction  and  refinement  of  animal  use  in  scientific  procedures. 
Recital  12  of  the  Directive  stipulates  that  "the  use  of  animals  for  scientific  or  educational  purposes 
should [therefore] only be considered where a non-animal alternative is unavailable. Use of animals 
for scientific procedures in other areas under the competence of the Union should be prohibited." 

Policy context  

EURL ECVAM primarily focuses on regulatory safety testing (with emphasis on chemicals over the 
last  4  years)  required  under  various  EU  legislations  such  as  Regulation  1223/2009  on  cosmetic 
products, Regulation (EC) No 1907/2006 concerning the Registration, Evaluation, Authorization and 
Restriction of Chemicals (REACH), Regulation (EC) No 1272/2008 on Classification, Labelling and 
Packaging of substances and mixtures (CLP), Regulation (EC) No 1107/2009 concerning the placing 
of  plant  protection  products  on  the  market,  Regulation  283/2013  on  data  requirements  for  active 
substances,  Regulation  284/2013  on  data  requirements  for  plant  protection  products,  Regulation 

39 Commission of the European Communities (1991). Communication from the Commission to the Council and the 
European Parliament on the establishment of a European Centre for the Validation of alternative Methods. SEC (91) 1794. 
Brussels 29 June 1991. 
40 For reasons of readability, Three Rs and 3Rs are used interchangeably in this document.  

130 

 
 
 
 
                                                            
528/29012  concerning  the  making  available  on  the  market  and  use  of  biocidal  products,  Directive 
2001/83/EC (and amendments) on the Community code relating to medicinal products for human use, 
Directive 2001/82/EC (and amendments) on the Community code relating to medicinal products for 
veterinary use, Regulation 1829/2003 on genetically modified food and feed, the Community Strategy 
on combined exposures 'Mixtures' and the Community Strategy on Endocrine Disrupters. 

The  above  cited  EU  Directives,  Regulations  and  Community  Strategies  are,  together  with  the 
horizontal Directive 2010/63/EU and Regulation 440/2008 on test methods,  the regulatory drivers for 
EURL  ECVAM's  work  on  alternatives.  All  these  pieces  of  legislation  either  refer  to  alternative 
approaches and/or allow them to be used in hazard, risk and safety assessments. 

Vertical  regulations  with  considerable  impact  on  the  Three  Rs  were  the  Cosmetics  Regulation  and 
REACH. The Cosmetics Regulation completely bans animal testing and the marketing in the EU of 
cosmetics  tested  on  animals  altogether  since  2013,  while  REACH  requires  since  2008,  that  animal 
tests are used only as a very last resort when no other, validated and approved non-animal tests are 
available. Moreover, recent updates of the REACH annexes for more advanced endpoints makes the 
use  of  validated  and  accepted  non-animal  tests  the  default  information  requirement  for  assessing 
whether  chemicals  have  the  potential  to  cause  these  hazards,  irrespective  of  the  tonnage  level  of 
production.  

In the area of human and veterinary medicinal products, non-clinical testing and quality control often 
requires  the  use  of  animals  to  comply  with  Directives  2001/83/EC  and  2001/82/EC  and  their 
associated  guidelines  and/or  pharmacopoeia  monographs.  Ethical  and  animal  welfare  considerations 
demand  that  animal  use  is  limited,  if  not  avoided,  as  much  as  possible.  In  this  respect,  Directive 
2010/63/EU  on  the  protection  of  animals  used  for  scientific  purposes,  which  is  fully  applicable  to 
regulatory  testing  of  human  and  veterinary  medicinal  products,  promotes  the  application  of  the 
principle of the Three Rs when considering choice of methods to be used (EMA, 2016). 

EMA recently established The Joint Committee for Medicinal Products for Veterinary Use/Committee 
for  Medicinal  Products  for  Human  Use  Working  Group  on  the  Application  of  the  Three  Rs  in 
Regulatory Testing of Medicinal Products (J3RsWG) replacing the formerly EMA expert group JEG 
3Rs  (2010  –  2016).  The  J3RsWG41  provides  advice  and  recommendations  to  the  Committee  for 
Medicinal  Products  for  Veterinary  Use  (CVMP)  and  Committee  for  Medicinal  Products  for  Human 
Use  (CHMP)  on  all  matters  relating  to  the  use  of  animals  and  the  application  of  the  Three  Rs 
principles in the testing of medicines for regulatory purposes.  

New structures provided by the Directive and enlarged scope for EURL ECVAM  

Other provisions of Directive 2010/63/EU had an impact on EURL ECVAM's work. For instance, as 
a response to Article 47(2) which requires that Member States assist the Commission in identifying 
and nominating suitable specialised and qualified laboratories to carry out validation studies, EURL 
ECVAM set up a European Union Network of Laboratories for the Validation of Alternative Methods 
(EU-NETVAL)  in  2014.  This  network,  coordinated  by  EURL  ECVAM,  currently  comprises  37 
members (from 15 EU Member States and EFTA countries) which were selected through open calls 
and against pre-defined eligibility criteria and endorsed by the National Contact Points of the Member 
States for the implementation of Directive 2010/63/EU.  

EU-NETVAL has a potential to significantly increase the European Union's validation capacity of in 
vitro methods by generating in vitro method information that is reliable, relevant and based on current 
best quality and scientific practices and provides a laboratory network knowledgeable on the routine 

41http://www.ema.europa.eu/ema/index.jsp?curl=pages/contacts/CVMP/people_listing_000094.jsp&mid=WC
0b01ac05803a9d6d#COM 

131 

 
 
 
                                                            
implementation of good in vitro method practices for regulatory use in human safety assessment. EU-
NETVAL members support validation studies through the execution of one or more specific tasks and 
also contribute to the development of guidance documents and training materials supporting good  in 
vitro  method  development  and  practices42.  However,  the  capacity  for  EU-NETVAL  members  to 
participate  actively  is  largely  dependent  on  funding  made  available  by  the  Member  States  to  their 
respective EU-NETVAL members. Some Member States have clearly seen this as one of the practical 
ways  to  respond  to  Article  47(1)  requirement  to  contribute  to  the  development  and  validation  of 
alternative approaches. It is hoped that more Member States will follow suit to enable EU-NETVAL 
to reach its full potential. 

Similarly,  Article  47(5)  requires  that  Member  States  nominate  a  single  point  of  contact  to  provide 
advice on the regulatory relevance and suitability of alternative approaches proposed for validation. 
The Preliminary Assessment of REgulatory Relevance (PARERE) Network was established by EURL 
ECVAM  in  2011.  The  network  is  composed  of  regulators  nominated  by  the  EU  Member  States, 
representatives  from  EU  regulatory  agencies  such  as  the  European  Medicines  Agency  (EMA),  the 
European Chemicals Agency (ECHA) and the European Food Safety Authority (EFSA), and relevant 
Commission  services.  In  order  to  expedite  the  process  of  regulatory  acceptance  of  alternative 
methods,  it  was  considered  that  regulators  should  be  involved  as  early  as  possible  in  providing  a 
preliminary view on the potential regulatory relevance of methods submitted to EURL ECVAM for 
validation.   PARERE  has  additional  tasks  which  are  described  on  the  EURL  ECVAM  website43. 
Finally  Article  47  (6)  asks  the  Commission  to  take  appropriate  action  with  a  view  to  obtaining 
international  acceptance  of  alternative  approaches  validated  in  the  Union.  Besides  involving 
regulators  early  on  in  the  evaluation  process  of  new  tests  and  approaches,  EURL  ECVAM  also 
reinforced its support to the OECD test guideline programme by leading the drafting of several new 
OECD  Test  Guidelines  or  Guidance  Documents  and  the  review  process  by  the  OECD  member 
countries. In addition, EURL ECVAM supports the EU National Coordinator and participates at the 
annual  meeting  of  the  Working  Group  of  National  Coordinators  of  the  OECD  Test  Guideline 
Programme  and  at  many  expert  meetings  on  specific  human  health  or  environmental  effects.  The 
Mutual  Acceptance  of  Data  Agreement  (MAD)  is  the  main  instrument  at  the  OECD  to  ensure  a 
globally  harmonised  approach  to  the  testing  and  assessment  of  chemicals.  This  reduces  costs  and 
saves  thousands  of  animals  every  year.  The  OECD  is  also  the  default  route  for  taking  up  new  test 
methods into the EU Test Method Regulation No 440/2008. International cooperation is also taking 
place  through  the  International  Cooperation  on  Alternative  Test  Methods  (ICATM)44.  ICATM 
includes governmental organisations from the EU, US, Japan, Canada, South Korea, Brazil and China 
who  are  working  together  to  promote  enhanced  international  cooperation  and  coordination  on  the 
scientific development, validation and regulatory use of alternative approaches. 

In line with Annex VII (e), EURL ECVAM also established in 2011 the ECVAM Stakeholder Forum 
(ESTAF)  to  maintain  dialogue  with  the  Stakeholder  community  involving  industrial  associations, 
research organisations and civil society. Through ESTAF, EURL ECVAM maintains close dialogue 
with  and  between  stakeholders  concerning  new  activities,  trends,  scientific  and  technical  issues, 
forward-looking aspects of test method development, optimisation, validation and use. Information on 
the  membership  and  roles  of  ESTAF  and  outcomes  of  meetings  can  be  retrieved  from  the  EURL 
ECVAM website45. 

42 https://eurl-ecvam.jrc.ec.europa.eu/eu-netval/EU-NETVAL-tor-november-2013.pdf 
43 https://eurl-ecvam.jrc.ec.europa.eu/about-ecvam/scientific-advice-stakeholders-networks/parere 
44 https://eurl-ecvam.jrc.ec.europa.eu/about-ecvam/networks-and-collaborations/collaboration-with-icatm 
45 https://eurl-ecvam.jrc.ec.europa.eu/about-ecvam/scientific-advice-stakeholders-networks/estaf-ecvam-stakeholder-
forum 

132 

 
 
 
                                                            
In 2010, the ECVAM Scientific Advisory Committee (ESAC) has been reformed and restructured in 
line with other scientific committees of the European Commission to ensure a clear separation of the 
provision  of  independent  scientific  advice  from  any  vested  interests.  Consequently,  the  ESAC  has 
been  renewed  in  2010  (with  a  mandate  of  3  years)  and  again  in  2013  and  only  includes  senior 
scientists selected on the basis of their scientific expertise and who are required to act independently 
and  on  the  basis  of  scientific  considerations.  The  selection  of  candidates  for  the  next  renewal  is 
underway.  ESAC's  main  role  is  to  conduct  independent  peer  reviews  of  validation  studies  of 
alternative  test  methods,  assessing  their  scientific  validity  for  a  given  purpose46. Since  2010, ESAC 
scientifically  peer  reviewed  16  methods  and  validation  studies  in  the  areas  of  skin  sensitisation, 
serious  eye  damage/eye  irritation,  skin  irritation,  acute  toxicity,  carcinogenicity  and  acute  aquatic 
toxicity. Notably, over the years, the number of validation studies which were carried out externally 
(i.e.  not  coordinated  or  carried  out  by  EURL  ECVAM)  and  submitted  to  EURL  ECVAM  for 
evaluation and ESAC peer review has considerably increased. The ESAC's advice to EURL ECVAM 
is  formally  provided  as  ESAC  working  group  reports  and  ESAC  Opinions  at  the  end  of  the  peer 
review  process.  ESAC's  advice  serves  as  the  basis  for  the  development  of  EURL  ECVAM 
Recommendations that summarise EURL ECVAM's view on the validity of a test method and advise 
on  its  possible  regulatory  applicability,  limitations  and  proper  scientific  use47.  EURL  ECVAM 
Recommendations  identify  knowledge  gaps  and  define  follow-up  actions.  Developed  in  close 
dialogue  with  regulators  (PARERE),  stakeholders  (ESTAF)  and  international  partners  (within  the 
framework  of  ICATM),  EURL  ECVAM  Recommendations  prepare  and  support  the  international 
recognition and regulatory use of alternative methods as well as their application by end users48 (see 
figure 1). 

Progress made in the EU on alternatives since 2010 

international  adoption  of  alternative  approaches 

Since 2010, considerable progress has been made in the EU in the development, validation, regulatory 
acceptance  and 
the  areas  of  skin 
irritation/corrosion,  serious  eye  damage/eye  irritation,  skin  sensitisation  and  phototoxicity  for  the 
human health-related effects, and aquatic toxicity testing for environmental effects.  In these areas the 
underpinning  science  is  more  advanced  and  mature  alternative  methods  and  knowledge  on  how  to 
optimally  combine  them  in  integrated  approaches  are  available  (Zuang  et  al.,  2013;  Zuang  et  al., 
2014; Zuang et al., 2015; Zuang et al., 2016). Notably, the development and validation of promising 
methods  in  these  areas  and  their  international  adoption  (e.g.  through  inclusion  into  OECD  Test 
Guidelines) led to changes in EU legislation. 

in 

Human health effects 

New amendments to the REACH Annexes VII and VIII regarding skin corrosion/irritation (point 8.1 
of Annexes VII and VIII), serious eye damage/eye irritation (point 8.2 of Annexes VII and VIII) and 
skin sensitisation (point 8.3 of Annex VII) entered into force in 2016 (EU, 2016a&b). The adopted in 
chemico  and  in  vitro  methods  are  now  the  default  requirement  and  in  vivo  studies  can  only  be 
conducted in exceptional cases, i.e. when the non-animal test methods are not applicable, or if the test 
results are not adequate for classification and risk assessment.  

At the International Conference on the Harmonisation of Technical Requirements for Registration of 
Pharmaceutical  Products  for  Human  Use  (ICH),  the  3T3  Neutral  Red  Uptake  Phototoxicity  Test 
adopted  as  OECD  TG  432  in  2004  was  included  in  ICH  S10  on  photosafety  evaluation  of 

46 https://eurl-ecvam.jrc.ec.europa.eu/about-ecvam/scientific-advice-stakeholders-networks/ecvam-scientific-advisory-
committee-esac 
47 https://eurl-ecvam.jrc.ec.europa.eu/eurl-ecvam-recommendations 
48 https://eurl-ecvam.jrc.ec.europa.eu/validation-regulatory-acceptance/eurl-ecvams-validation-process 

133 

 
 
 
 
                                                            
pharmaceuticals in 2014. The guideline considered the recommendations made at the joint ECVAM-
EFPIA49 workshop of 2010 (Ceridono et al. 2012) to better define how data based on OECD TG 432 
can be used for risk assessment of pharmaceuticals. 

For acute systemic toxicity, reduction in the animal use could be achieved through the amendment of 
REACH  annex  VIII  (point  8.5).  An  acute  dermal  toxicity  study  can  now  be  waived  for  those 
substances which are non-toxic via the oral route. This amendment was possible due to the scientific 
evidence indicating that substances demonstrated to be of low acute toxicity by the oral route are also 
of low toxicity by the dermal route and, therefore, that dermal testing for acute systemic toxicity of 
such substances adds nothing to the hazard characterisation.  

EURL  ECVAM  published  its  strategy  to  replace,  reduce  and  refine  the  use  of  animals  in  the 
assessment of acute mammalian systemic toxicity50 which highlights additional options for achieving 
Three  Rs  impact,  like  for  instance  the  better  use  of  existing  alternative  methods  such  as 
mechanistically relevant in vitro assays, as well as existing information on repeated dose toxicity, and 
collecting and organising mechanistic knowledge related to this health effect in order to improve the 
design and validation of predictive models and approaches. 

In the area of genotoxicity, progress has been made on the overall improvement of the current testing 
strategy for better hazard assessment with the use of fewer or no  animals to satisfy the information 
requirements of various pieces of EU legislation.  As outlined in the EURL ECVAM Strategy to avoid 
and reduce animal use in genotoxicity testing51 this includes enhancing the performance of the in vitro 
testing battery so that fewer in vivo follow-up tests are necessary and guiding more intelligent in vivo 
follow-up testing to reduce and optimise the use of animals. In this context, a considerable number of 
activities  have  been  carried  out  in  the  EU  and  worldwide  with  the  aim  of  optimising  strategies  for 
genotoxicity testing and harmonising the genotoxicity safety assessment across sectors. For instance, 
the OECD has recently updated almost all the genotoxicity test guidelines and is currently investing in 
a retrospective analysis of available miniaturised tests for gene mutation in bacteria. Additionally, the 
OECD  is  taking  up  the  discussion  on  innovative,  more  mechanistically-based  in  vitro  genotoxicity 
methods.  EURL  ECVAM  recently provided  the  scientific  and  regulatory  community  with a  curated 
genotoxicity and carcinogenicity database52 which, together with a recommended list of genotoxic and 
non-genotoxic  chemicals  for  assessing  the  performance  of  new  in  vitro  genotoxicity  test  methods 
(Kirkland  et  al,  2016)  have  become  powerful  tools  for  data  analysis  and  in  vitro  genotoxicity  tests 
development and improvement. It is worth noting that changes to the in vitro testing battery (Kirkland 
et  al.,  2011)  have  been  adopted  in  the  safety  assessment  of  substances  in  food  and  feed  by  EFSA 
(EFSA, 2011), as well as for cosmetics ingredients in the EU (SCCS, 2015).  

Exposure  to  a  chemical  does  not  automatically  mean  that  all  of  the  dose  will  be  bioavailable  and 
therefore able to cause a specific toxicity. Information on the human toxicokinetics (the biological fate 
of a substance in the human body) plays thus an important role in human safety assessment. Current 
EU  test  methods  and  OECD  test  guidelines  are  mostly  based  on  animal  procedures.  However  the 
integration of new technologies such as in vitro methods and computer models allows the prediction 
of absorption, distribution, metabolism and excretion (ADME), the four underlying processes driving 
toxicokinetic  behaviour.  In  general  however,  the  lack  of  standardisation  of  these  methods  is 
hampering  their  regulatory  acceptance  and  use.  Efforts  are  thus  focused  on  the  characterisation  and 
description  of  human  in  vitro  absorption,  distribution,  metabolism  and  excretion  (ADME)  methods 
and  on  good  modelling  practice.  Human  hepatic  metabolic  clearance  (HHMC)  represents  in  many 

49 European Federation of Pharmaceutical Industries and Associations 
50 https://eurl-ecvam.jrc.ec.europa.eu/eurl-ecvam-strategy-papers/strategy-acute-mammalian-systemic-toxicity 
51 https://eurl-ecvam.jrc.ec.europa.eu/eurl-ecvam-strategy-papers/strat-genotoxicity 
52 https://eurl-ecvam.jrc.ec.europa.eu/databases/genotoxicity-carcinogenicity-db 

134 

 
 
 
 
                                                            
cases the main driving process of kinetics to determine the concentration-time profile of a chemical in 
a  biological  system  and  is  an  indispensable  information  source  to  support  the  chemical  risk 
assessment.  A  call  for  submission  of  in  vitro  human  hepatic  metabolic  clearance  methods  triggered 
the submission of 15 HHMC methods that aim to measure in vitro the rate at which a test chemical is 
metabolised  by  a  human  liver-based  test  system.  A  new  project  aiming  at  developing  a  Guidance 
Document  for  the  characterisation  and  description  of  in  vitro  hepatic  metabolic  clearance  methods 
was  recently  submitted  to  the  OECD.  This  Guidance  Document  is  focused  on  the  use  of  in  vitro 
methods  to  measure  hepatic  metabolic  clearance  as  a  proxy  to  information  derived  from  in  vivo 
metabolism studies.   

Most of the in vitro methods which were developed and submitted to EURL ECVAM for validation 
and/or  peer  review  from  2010  to  2016  were  in  the  areas  of  (in  decreasing  order)  skin  sensitisation, 
skin  and  eye  irritation  (including  several  similar  methods  to  already  validated  and  adopted  ones), 
endocrine disruption and genotoxicity. These areas are of particular interest to the cosmetics industry 
which  is  facing  since  2009  an  animal  testing  ban  for  cosmetic  ingredients  and  products  and  since 
2013, a complete ban on the marketing, inside of the EU, of cosmetic ingredients and products tested 
on  animals  and  which,  therefore,  has  invested  in  the  development  of  non-animal  methods  in  these 
areas.   

With  regard  to  endocrine  disrupters,  the  OECD-endorsed  methods  are  grouped  in  a  conceptual 
framework (CF) for the testing and assessment of endocrine disrupters which includes five different 
levels.  Level  two  of  this  CF  includes  in  vitro  assays  which  provide  data  on  selected  endocrine 
mechanism(s) / pathways, such as hormone receptor binding and transactivation assays. Some of these 
methods had been developed within ReProTect53 project under the 6th EU Framework Programme (as 
well as internationally) for screening purposes and identification of target mechanisms of endocrine 
active  compounds.  The  submitted  test  methods  were  either  binding  assays  or  transcriptional  assays 
measuring  either  androgenic  or  estrogenic  activity  which  could  fit  into  the  OECD  conceptual 
framework. Successful validation and peer review of several estrogen-receptor transactivation assays 
led to the inclusion of these test methods into an OECD Performance-Based Test Guideline (OECD 
PBTG 455). An Androgen-Receptor Transactivation assay (ARTA) is currently undergoing a EURL 
ECVAM  coordinated  validation  study  in  three  of  the  EU-NETVAL  laboratories.  If  successfully 
validated,  this  method,  together  with  other  validated  ARTAs,  will  be  included  in  an  OECD 
Performance-Based  Test  Guideline  on  ARTAs.  Other  assays  have  recently  been  validated  for  the 
detection of chemicals with estrogen binding affinity, leading to the development of a Performance-
Based  Test  Guideline  (PBTG  493).  Another  recently  validated  test  measuring  the  effects  on 
steroidogenesis was adopted as OECD TG 456.  

A  number  of  in  vitro  assays  evaluating  different  aspects  of  perturbation  of  the  estrogen-signalling 
pathway has recently been combined in a computational model by the US Environmental Protection 
Agency . The model has a good concordance with an in vivo rodent model also evaluating interference 
with  estrogen  signalling  (Browne  et  al.,  2015).  This  provides  an  interesting  example  of  a  possible 
replacement of a current in vivo mechanistic screening assay. Other activities are ongoing to identify 
knowledge  gaps  and  validation  needs  on  less  known  endocrine  pathways  such  as  the  thyroid  or  the 
retinoid pathways. 

For  complex  endpoints  such  as  repeated-dose  toxicity,  carcinogenicity  and  reproductive  toxicology, 
the  lack  of  suitable  and  mechanistically  based  methods  and  their  optimal  integration  in  regulatory 
testing  frameworks  remains  a  challenge.  The  few  methods  which  are  developed  and  submitted  in 
these areas usually model only one specific mechanism of toxicity that may lead to an adverse effect. 

53 The project ReProTect (2005-2010) aimed at the development of new in vitro tests to replace animal experimentation in 
reproductive toxicology 

135 

 
 
 
                                                            
In  these  cases  where  there  is  a  need  to  identify  complementary  endpoints  that  would  have  to  be 
assessed  with  other  in  vitro/in  silico  methods  and  where  conceptual  frameworks  or  Integrated 
Approaches to Testing and Assessment (IATA) are not yet available, regulators are more reluctant to 
use the results of these methods to inform regulatory decision making. These non-standardised assays 
then  usually  remain  at  the  level  of  screening  tools  within  industry  to  aid  in  the  prioritisation  of 
substances and are not used for regulatory risk assessment purposes.  

Research  projects  therefore  continue  to  be  funded  by  the  European  Commission  in  these  complex 
areas.  For  example,  the  Seurat-154  project  co-funded  by  the  European  Commission  and  Cosmetics 
Europe55 under the 7th EU Framework Programme focused on the safety assessment of chemicals for 
replacing  animal  testing  for  repeated  dose  toxicity.  This  initiative  attempted  to  address  the  safety 
assessment of chemicals for regulatory use through a series of case studies. It also provided a toolbox 
developed by the different projects resulting in a large variety of alternative methods, techniques and 
compiled information, which is available through various databases and websites such as ToxBank56, 
DB-ALM57, COSMOS  Space58, COSMOS  KNIME WebPortal59 and COSMOS  Database60. Another 
recent  project  funded  by  the  European  Commission  under  Horizon2020,  under  the  name  of  EU-
ToxRisk,  is  building  further  on  the  activities  started  by  the  SEURAT-1  initiative.  EU-ToxRisk 
continues  to  evaluate  methodologies  for  repeated  dose  toxicity,  but  also  for  developmental  and 
reproductive  toxicity.  The  project  is  built  up  around  different  case  studies  to  better  capture 
possibilities and shortcomings in safety assessment applications.  

Developmental  neurotoxicity  (DNT)  represents  another  complex  endpoint.  In  October  2016,  an 
OECD/EFSA Workshop on DNT61 was organised in an effort to develop a consensus on which testing 
battery of alternative DNT methods could be already applied and used in a fit-for-purpose manner for 
different  regulatory  needs,  i.e.,  chemical  screening  for  prioritisation,  or  hazard  identification  for 
specific chemical risk assessment. In recent years, several in vitro assays which assess the impact of 
chemicals  on  cellular  processes  critical  to  normal  brain  development  have  been  developed.  In 
particular,  assays  suitable  to  measure  neural  proliferation,  differentiation,  migration,  neurite 
outgrowth, synaptogenesis, and neural activity have been used to derive mechanistic information for 
limited  numbers  of  chemicals,  and  a  few  of  them  have  been  used  to  screen  large  numbers  of 
chemicals (Bal-Price et al., 2015). In the longer term, it is expected that in vitro test guidelines will be 
developed, with a view to achieving a harmonised approach to their regulatory use across countries. 

All these research and development activities in the field of alternatives predominantly focus on the 
integration  of  a  variety  of  testing  and  non-testing  methods  such  as  in  vitro  technologies, 
bioinformatics and computational toxicology into Integrated Approaches to Testing and Assessment 
(IATA).  Ideally  and  if  available,  such  IATA  are  based  on  Adverse  Outcome  Pathways  (AOP),  a 
mechanistic  knowledge  framework  that  describes  a  logical  sequence  of  causally  linked  events  at 
different  levels  of  biological  organisation,  which  follows  exposure  to  a  chemical  and  leads  to  an 
adverse  health  effect  in  humans  or  environment.  The  AOP  concept  was  developed  to  better 
understand, explain and organise the steps that link perturbation of a biological system to an adverse 
(apical)  outcome.  This  in  turn  should  help  to  guide  the  development  of  relevant  methods  and  their 

54 http://www.seurat-1.eu/ 
55 The European Cosmetics Industry Trade Association 
56 http://toxbank.net/  
57 EURL ECVAM's Database on Alternative Methods: 
 https://ecvam dbalm.jrc.ec.europa.eu/  
58 http://cosmosspace.cosmostox.eu/   
59 https://knimewebportal.cosmostox.eu/ 
60 https://cosmosdb.eu/cosmosdb.v2/ 
61 https://www.efsa.europa.eu/sites/default/files/event/161018b-a.pdf 

136 

 
 
 
                                                            
most  optimal  combination  to  appropriately  mimic  the  entire  range  of  key  biological  events  from 
exposure to a xenobiotic to the adverse outcomes of concern for humans or environment.  

Activities at the OECD level to develop an IATA framework for the identification of non-genotoxic 
carcinogens  go  into  that  direction.  In  fact,  it  has  been  estimated  that  10-20%  of  recognised  human 
carcinogens classified as Class 1 by the International Agency for Research on Cancer (IARC) act by 
non-genotoxic  mechanisms  (Hernandez  et  al.  2009).  However,  for  virtually  all  OECD  regulatory 
jurisdictions, including REACH, there are no specific requests to obtain information on non-genotoxic 
mechanisms  of  carcinogenicity  specifically.  Moreover,  as  mentioned  above,  there  are  no  in  vitro 
methods  available  yet.  It  thus  appears  likely  that  many  non-genotoxic  carcinogens  may  remain 
unidentified and the risks they may pose to human health will not be managed.  
Of  particular  interest  is  also  the  proposal  to  change  the  actual  carcinogenicity  testing  approach  for 
pharmaceuticals (ICH, 2016), in order to satisfy Directive 2010/63/EU. The proposal is based on the 
concept that "a weight of evidence evaluation can, in certain cases provide sufficient information to 
conclude that a given pharmaceutical presents a negligible risk or, conversely, a likely risk of human 
carcinogenicity  without  conducting  a  two-year  rat  carcinogenicity  study".  A  prospective  evaluation 
study  to  confirm  the  above  hypothesis  has  been  undertaken  (ICH,  2016).  Preliminary  analyses  are 
ongoing (e.g. within EPAA) to investigate if this approach could be translated to other sectors, where 
only 90-day repeated dose toxicity studies are available (Woutersen et al., 2016). A positive outcome 
from  this  exercise  could  change  the  classical  way  of  approaching  carcinogenicity  testing  and  might 
yield a significant reduction in the conduct of two-year cancer studies and a consequent reduction in 
number of animals used. 

Environmental effects  

In  environmental  toxicology,  the  assessment  of  aquatic  toxicity  and   bioaccumulation  are  important 
components  of  the  environmental hazard and risk  assessment of  all  types  of  chemicals  and  are 
therefore  information  requirements  in  several  pieces  of  EU  and  international  legislation.  EURL 
ECVAM  published  its  strategy  to  replace,  reduce  and  refine  the  use  of  fish  in  aquatic  toxicity  and 
bioaccumulation  testing62  in  2013.  If  successfully  implemented  by  all  key  actors,  the  strategy  will 
deliver alternative approaches that address standard information requirements in many sectors while 
ensuring that animal testing is only conducted as a last resort. One important near-term impact could 
be  the  reduction  of  animal  testing  necessary  for  the  implementation  of  REACH and  the  2018 
registration deadline. EURL ECVAM focused its in-house activities on promoting the use of available 
alternative methods for fish acute toxicity testing, on exploring the usefulness of scientific approaches 
(e.g. acute-to-chronic relationships) to facilitate the waiving of chronic fish tests, and on supporting 
activities at OECD level. 

Recent achievements are linked to acute fish toxicity testing. The OECD Guidance Document (GD) 
126 "Short guidance on the use of the threshold approach for acute fish toxicity testing" is available 
since  2010  (OECD,  2010)  and  describes  a  tiered  testing  strategy  which  has  the  potential  to 
significantly reduce the number of fish used for acute aquatic toxicity testing. The threshold approach 
has  been  incorporated  into  various  testing  strategies  and  guidance  documents,  e.g.  the  REACH 
guidance on information requirements and chemical safety assessment (ECHA, 2016) and the OECD 
Fish  Toxicity  Testing  Framework  (OECD,  2012).  It  is  further  mentioned  as  a  preferred  method  for 
deriving  data  on  acute  fish  toxicity  in  the  biocidal  products  regulation  (EU,  2012)  and  in  the 
Commission regulations on data requirements for plant protection products (EU, 2013a & b).  

The validated zebrafish embryo acute toxicity test method (ZFET; Busquet et al., 2014) was included 
in OECD TG236 in 2013. EURL ECVAM recommends the ZFET for generating information on acute 

62 https://eurl-ecvam.jrc.ec.europa.eu/eurl-ecvam-strategy-papers/strategy-fish 

137 

 
 
 
 
                                                            
fish toxicity where appropriate (EURL ECVAM, 2014). Its use will result in an overall reduction of 
the  numbers  of  juvenile  and  adult  fish  for  aquatic  toxicity  testing.  In  2016,  ECHA  published  its 
"Analysis  of  the  relevance  and  adequateness  of  using  Fish  Embryo  Acute  Toxicity  test  (FET)  Test 
Guideline  (OECD  236)  to  fulfil  the  information  requirements  and  addressing  concerns  under 
REACH"63. ECHA concluded that, at present, the FET can be used in a weight-of-evidence approach 
and published a summary of ECHA's view64.   

With regard to chronic fish toxicity testing, EURL ECVAM has recommended options for avoiding 
chronic fish testing on the basis of existing data and extrapolation approaches (Kienzler et al., 2016).  
In particular, it was concluded that interspecies extrapolations and acute-to-chronic relationships can 
be used to scientifically support the waiving of chronic fish tests, according to the specific mode of 
action. 

Moreover,  EURL  ECVAM  is  co-leading  two  OECD  projects,  i.e  the  reduction  of  the  number  of 
control  fish  (co-lead  with  ICAPO)  and  drafting  of  test  guidelines  to  derive  fish  in  vitro  hepatic 
clearance (co-lead with USA; for detailed information see EURL ECVAM Status Report 2016). 

Quality control of pharmaceuticals 

With respect to the quality control of pharmaceuticals, EURL ECVAM's focus is mainly on vaccines 
since,  traditionally,  animals  have  played  an  important  role  in  quality  control  of  vaccines  and  many 
animals are still used in Europe for this purpose. Over the last decades, several Three Rs methods to 
classical  animal  tests  have  been  developed  by  control  authorities,  academia  and  vaccine 
manufacturers, validated within the framework of the Biological Standardisation Programme65 (BSP) 
of the European Directorate for the Quality of Medicines & HealthCare (EDQM; Council of Europe) 
and incorporated into European Pharmacopoeia monographs.  

In  2015,  EURL  ECVAM  released  a  report  on  Replacement,  Reduction  and  Refinement  of  Animal 
Testing  in  the  Quality  Control  of  Human  Vaccines66.  The  focus  of  the  report  is  on  methods  for  lot 
release  testing  (e.g.  safety,  pyrogenicity,  potency)  and  projects  related  to  the  implementation  of  the 
consistency  approach  to  established  vaccines  such  as  diphtheria,  tetanus,  pertussis  and  rabies 
vaccines.  The  report  shows  that  progress  has  been  achieved  and  new  approaches  to  quality  control 
such as the consistency approach have the potential to further reduce animal use. 

Within  the  EPAA67,  EURL  ECVAM  organised  in  collaboration  with  vaccine  manufacturers  a 
workshop  to  discuss  the  consistency  approach  for  the  quality  control  of  vaccines  (De  Mattia  et  al., 
2011).  The  EPAA  Vaccines  Consistency  Approach  project  (2010  –  2016)  initiated  a  number  of 
activities  aiming  at  developing  and validating  non-animal  methods  with  the  support of  stakeholders 
from  academia,  regulators,  Official  Medicines  Control  Laboratories  (OMCLs),  EDQM,  European 
Commission  and  vaccine  manufacturers  (De  Mattia  et  al.,  2015)  summarised  the  work  carried  out 
within  the  four  priority  vaccines/vaccine  groups  (diphtheria/tetanus/acellular  pertussis  vaccines; 
human  rabies  vaccines;  veterinary  rabies  vaccines;  clostridial  vaccines).  Two  activities  resulted  in 

63 https://echa.europa.eu/documents/10162/13639/fet_report_en.pdf/b6036bdb-9041-41c8-a390-
d9b66b244a4b  

64 https://echa.europa.eu/documents/10162/21650280/oecd_test_guidelines_aquatic_en.pdf/2548af92-ffe1-4e38-a42a-
463103b1586f 
65 http://www.edqm.eu/en/BSP-Work-Programme-609.html; https://www.edqm.eu/en/BSP-programme-for-3Rs-
1534.html 

66 https://eurl-ecvam.jrc.ec.europa.eu/the-3rs-in-the-quality-control-of-human-vaccines-eurl-ecvam-releases-summary-of-
ongoing-projects 
67 European Partnership on Alternatives to Animal Approaches is a public-private partnership 

138 

 
 
 
                                                            
EDQM BSP studies and cover the validation of in vitro methods for in process control of a clostridial 
vaccine  and  potency  testing  of  rabies  vaccines  for  human  use.  The  EPAA  Vaccine  Consistency 
Approach project also promoted the inclusion of the topic into the Innovative Medicines Initiative 2 
(IMI 2) call published in 2014. IMI 2 is a Joint Undertaking of the European Union’s Horizon 2020 
research  and  innovation  programme  and  the  European  Federation  of  Pharmaceutical  Industries  and 
Associations (EFPIA). 

In March 2016, under the new Innovative Medecine Initiative (IMI)2 , the project "Vaccine batch to 
vaccine  batch  comparison  by  consistency  testing"  (VAC2VAC)  was  officially  launched  and  brings 
together  20  public  and  private  partners.  The  project  will  provide  data  to  support  the  consistency 
approach  for  quality  control  of  established  vaccines  for  human  and  veterinary  use.  The  consistency 
approach moves away from the current focus on final product control often relying on animal testing. 
In the light of this, VAC2VAC partners will develop, optimise and evaluate non-animal methods, e.g. 
physicochemical and immunochemical methods, cell-based and other assays for routine batch quality, 
safety  and  efficacy  testing  of  vaccines,  in  collaboration  and  consultation  with  regulatory  agencies. 
JRC/EURL ECVAM is participating in the project as leader of the work package related to validation, 
and  will  also  support  project  activities  related  to  international  dissemination,  harmonisation  and 
regulatory acceptance of consistency approaches. 

As  in  other  areas,  international  harmonisation  is  an  important  aspect  also  for  the  quality  control  of 
vaccines. Since 2008 and on behalf of EMA, EURL ECVAM is working with VICH experts on the 
development of guidelines on harmonisation of criteria to waive the target animal batch safety testing 
for inactivated and live vaccines for veterinary use. VICH GL50  for inactivated veterinary vaccines 
was adopted in 2013 and is in force since 1st March 2014 (VICH, 2013). The comparable VICH GL55 
for live veterinary vaccines and the revised VICH GL50 underwent public consultation in 2016 and 
are currently being finalised for adoption by the VICH Steering Committee. A third guideline is under 
development  aiming  at  the  harmonisation  of  criteria  to  waive  the  general  batch  safety  test  in 
laboratory  animals  (e.g.  abnormal  toxicity  test).  Both,  the  abnormal  toxicity  test  and  target  animal 
batch safety testing have been deleted from European Pharmacopoeia  monographs several years ago 
(Schwanig et al., 1997; EDQM, 2012). However, since they may still be required outside of Europe, 
European manufacturers may need to carry out these tests when exporting to third countries. 

EURL ECVAM is a member of the EPAA project "Biologicals" aiming at progressing harmonisation 
of requirements for batch testing of vaccines and other biological products at a global level. Due to 
evident differences in the current regional requirements, manufacturers may need to carry out animal 
tests which are no longer required in Europe, if they want to market their products outside of Europe. 
EPAA  convened  an  international  workshop  (15-16  September  2015)  with  representatives  from 
regulatory  bodies  and  manufacturers  to discuss  steps  towards  deletion  of  general  safety  tests  and  to 
identify  means  towards  implementation  of  in  vitro  methods  for  potency  testing  of  human  and 
veterinary  vaccines.  The  workshop  report68  "Modern  science  for  better  quality  control  of  medicinal 
products:  Towards  global  harmonisation  of  3Rs  in  biologicals"  is  available  on  the  EPAA  website. 
The major recommendation – agreed by all participants – is the deletion of general safety tests, e.g. 
abnormal  toxicity  test,  target  animal  batch  safety,  from  regulatory  requirements  at  a  global  level. 
Nowadays, these tests lack scientific relevance and their omission does not compromise the safety of 
vaccines, or any other pharmaceutical, since more adequate quality control measures are in place. The 
project  team  is  following  up  the  recommendations  in  collaboration  with  workshop  participants  and 
relevant stakeholders. 

Dissemination 

68 https://circabc.europa.eu/sd/a/4a081e45-f19f-47f7-8d8d-65f4f10fccff/ihb%20sept%202015%20report.pdf 

139 

 
 
 
                                                            
In  order  to  disseminate  information  on  alternative  approaches  and  enhance  overall  progress  in  their 
use, several database services are available at EURL ECVAM (Zuang et al., 2016).  One service that 
is  well-known  is  the  EURL  ECVAM’s  DataBase  service  on  ALternative  Methods  to  animal 
experimentation  (DB-ALM)  that  provides  ready-to-use  and  evaluated  information  about  the 
application  and  development  status  of  advanced  alternative  methods  in  a  standardised  manner. 
Information at various level of detail is provided and defined according to pre-determined criteria for 
data content by experts in the field. Current focus is given to in vitro methods and non-experimental 
approaches used for safety assessments of chemicals and/or formulations, but also includes methods 
for testing drugs or biologicals or for research purposes. The DB-ALM is a widely used public service 
with steady increasing interest and usage. To date, it can refer to more than 5000 registrations from 
over  82  countries  covering  users  from  academia,  industry,  regulatory  communities  and  the  animal 
welfare movement. 

Since  2015,  the  DB-ALM  Method  Summary  data  sector  provides  a  harmonised  framework  for 
adequately describing alternative methods in an OECD accepted format69. 

EURL  ECVAM  also  revised  its  Tracking  System  for  Alternative  Test  Methods  towards  Regulatory 
acceptance  (TSAR70).  TSAR  serves  to  track  progress  of  an  alternative  method,  in  a  transparent 
manner,  from  proposal  for  validation  through  to  its  final  adoption  and  inclusion  into  the  regulatory 
framework  (EU,  OECD  and  other  related  standards).  TSAR  includes  summary  descriptions  of 
individual  methods  and  all  available  records  associated  with  different  steps  of  the  validation  and 
acceptance process. TSAR disseminates information on test methods not only under consideration by 
EURL  ECVAM  but  by  all  member  organisations  of  ICATM.  In  this  way  an  overall  view  of  the 
methods under evaluation by all international validation centres is provided from one access point. 

Of high relevance to Directive 2010/63/EU is the EURL ECVAM Search Guide71 (first published in 
2012  with  a re-edition  in 2013).  It has  specifically been  developed  to  inform  and  support untrained 
database users in finding high quality information on relevant alternative methods and strategies from 
the  large  amount  of  available  information  resources  in  an  easy,  yet  systematic,  and  efficient  way 
during  project  preparations  in  biomedical  sciences.  It  is  used  as  a  resource  for  higher  education  in 
academic institutions in life sciences and by scientists and national authorities during the preparation 
and the evaluation of scientific projects that might involve animal use. It has now entered the Asian 
market where it was translated and re-published as a handbook and e-book in Korean. A Portuguese 
version is under development together with Brazilian Authorities within the framework of ICATM.     

EURL  ECVAM  is  further  investigating  Three  Rs  knowledge  sharing  opportunities  with  the  aim  to 
explore  how  sharing  of  knowhow  and  access  to  resources  could  be  enhanced  to  accelerate  overall 
progress  in  the  Three  Rs.  This  is  explored  in  every  domain  where  animals  are  used  for  a  scientific 
purpose,  be  it  for  basic  biological  research,  toxicological  testing,  or  for  training  and  education 
purposes. 

Conclusions 

Over the last decade, scientists and regulators have increasingly committed to the use of non-animal 
methods  in  the  area  of  regulatory  toxicity  testing.  Scientific  and  technological  progress,  negative 
public opinion towards severe animal testing procedures, as well as first successes in including non-
animal methods into EU legislation paved the way for this more collective endeavor. 

69 OECD Guidance Document N◦211 for describing non-guideline in vitro test methods 
70 Access to TSAR:  http://tsar.jrc.ec.europa.eu/ 
71 EURL ECVAM Search Guide available from the EU Bookshop 

140 

 
 
 
                                                            
The search for alternatives to animal procedures dates back to the early 90s in Europe and was mainly 
driven  by  ethical  concerns  towards  procedures  on  animals.  In  the  US,  an  important  milestone  for 
advancing  progress  in  this  area  occurred  in  2007  with  the  publication  by  the  National  Research 
Council of a vision and a strategy for toxicity testing in the 21st century (NRC, 2007) and subsequent 
massive testing programmes like ToxCast and Tox21, mainly driven by economic interests. 

Importantly, it has in general been recognised that new testing approaches often based on human cells 
and modeling mechanisms of human relevance could be more predictive and informative for human 
toxicity than the traditional tests based on animals. Notably also, the testing could be faster, cheaper 
and  more  efficient,  in  particular  when  assays  are  amenable  to  high-throughput  and  high-content 
screening.   

However,  for  achieving  a  complete  shift  from  the  traditional  testing  on  animals  to  modern  toxicity 
testing  using  a  combination  of  in  silico  and  in  vitro  methods  only,  there  is  still  some  way  to  go. 
During this transition period it is therefore important that Directive 2010/63/EU is fully implemented.  
Thanks to that directive, rules on animal use are harmonised across the EU and meet high standards 
which should increase the welfare of animals in scientific research and testing. 

It  should  also  be  borne  in  mind  that  the  safety  testing  of  chemicals  accounts  for  less  than  10%  of 
animals  used  in  the  EU  and  that  most  animals  are  used  for  research  purposes.  Provisions  in  the 
directive  to  establish  animal  welfare  bodies  within  the  National  Committees;  systematic  project 
evaluation  by  a  competent  authority  of  any  proposed  use  of  live  animals;  specific  requirements  on 
education, training and competence of personnel; and a more detailed and comprehensive reporting on 
animals used for scientific purposes are all extremely important.  

It is difficult to judge if the directive had a direct impact on the number of alternative methods being 
developed,  validated  and  adopted.  The  development  of  new  methods 
(and  subsequent 
validation/evaluation  and  uptake)  mainly  occurs  when  funding  and  market  opportunities  arise.  This 
may  happen,  for  example,  when  a  sectorial  legislation  changes  (e.g.  banning  of  animal  testing  for 
cosmetic  ingredients).  However,  the  directive  raised  the  awareness  of  scientists,  in  particular  those 
working in research, regulators and legislators on the existence of alternative methods and approaches 
and the need to consider them. Therefore, continuing to increase awareness of the existence of Three 
Rs knowledge sources and free and easy access to them is crucial, starting with education across all 
three levels (i.e. high school, university and professional levels) extending to how, and in what form, 
this knowledge is communicated and disseminated to have an important positive impact.  

In conclusion, Directive 2010/63/EU is extremely valuable, however many other changes of scientific, 
economic, social, legal and political nature need to happen in parallel in order to make this "paradigm 
shift" finally a reality. 

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Figure  1:  The  role  of  EURL  ECVAM  in  the  evolution  of  regulatory  methods/approaches  and 
interactions with stakeholders 

144