Working to reduce the use of animals in research...8 D a elivering our Commitment to Replace, Reduce...
Transcript of Working to reduce the use of animals in research...8 D a elivering our Commitment to Replace, Reduce...
Working to reduce the use of animals in scientific research
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Delivering our Commitment to Replace, Reduce and Refine the Use of Animals in Research
Acknowledgements
This Delivery Plan has been developed in collaboration between the Home Office Animals in Science Regulation
Unit (ASRU), the Department for Business, Innovation and Skills (BIS) and Government Office for Science.
It reflects significant input from other government departments including the Department of Health (DH), the
Department for Environment, Food and Rural Affairs (Defra), the Food Standards Agency (FSA) and the Foreign &
Commonwealth Office (FCO) as well as a number of government agencies including Public Health England (PHE),
the Medicines and Healthcare Products Regulatory Agency (MHRA), the Veterinary Medicines Directorate (VMD),
the Animal Health & Veterinary Laboratories Agency (AHVLA), the Food & Environment Research Agency (Fera),
the Centre for Environment, Fisheries & Aquaculture Science (Cefas) and the Health & Safety Executive (HSE).
The National Centre for the Replacement, Refinement & Reduction of Animals in Research (NC3Rs) has made a
major contribution. The Government Chief Scientific Adviser and departmental Chief Scientific Advisers, as well as
experts from academia, the Research Councils and several government advisory committees, have also contributed
significantly to this work.
First published: February 2014URN BIS/14/589 ISBN 978-1-78246-264-4
© Crown copyright 2014
You may reuse this information (not including logos and photographs) free of charge in any format or medium,
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government-licence/ or write to the Information Policy Team, The National Archives, Kew, London TW9 4DU, or
email: [email protected]
Delivering our Commitment to Replace, Reduce and Refine the Use of Animals in Research
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Foreword
The Programme for Government commitment to work to reduce the use of animals in research brings together the UK’s long tradition of support for animal welfare alongside its strength in science and innovation. This document provides more detail on how we will continue to deliver our commitment while maintaining and reinforcing our position at the forefront of global science and innovation.
In this Plan, we bring together new and existing initiatives for promoting the widespread adoption of scientific and technological advances which present significant opportunities to replace animal use, to reduce the number of animals used and to refine the procedures involved so as to find additional ways to minimise suffering.
Delivery of this Plan is not simply a challenge for the Government and its agencies. If we are to be successful we need to enhance our partnerships with a wide range of stakeholders including the research community in both academia and industry and others with relevant animal research and welfare interests.
The UK is seen as a leader, globally, in the adoption of the 3Rs. This gives us a real opportunity to accelerate the international uptake of scientifically valid alternatives in research and safety testing. This work is very challenging and often involves agreement at inter-governmental level. However, the reward is to effect reductions in the volume of animal experiments on a
scale well above what can be achieved by domestic action alone. It will also benefit the UK Life Sciences sector (a key component of the Government’s Industrial Strategy) by ensuring that strict application of UK regulations does not simply export experiments abroad. Similarly, harmonising standards internationally will ensure that UK companies with high welfare standards are not shut out of large developing economies which may currently demand additional animal testing not required by most states.
Transparency and openness about the use of animals in research, and why their continued use remains necessary, helps to improve our overall understanding about the issue, enables an informed public dialogue and can help to mitigate anxieties and misunderstandings. An important part of our overall strategy is to build on the Declaration of Openness launched last year, driven by the academic sector, health charities and industry. This commits those engaged in research to foster an environment of openness around the ways in which animals are used in scientific research in the UK.
Through this Delivery Plan, we demonstrate how placing 3Rs approaches at the heart of a science-led programme will assure high standards of animal welfare while continuing to deliver benefits for humans, animals and the environment and UK economic growth.
The Rt Hon David Willetts MPMinister for Universities and ScienceDepartment for Business, Innovation and Skills
Lord Taylor of Holbeach CBELords Minister and Minister for Criminal InformationHome Office
The Rt Hon Earl HoweMinister for QualityDepartment of Health
Delivering our Commitment to Replace, Reduce and Refine the Use of Animals in Research
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Contents
Acknowledgements ....................................................................................................................2
Foreword ....................................................................................................................................3
Contents .....................................................................................................................................5
Introduction .................................................................................................................................7
Section 1: Setting the Scene .................................................................................................10
1.1 The continuing need to use animals in research ...............................................................10
1.2 What the Government is doing to promote the 3Rs ...........................................................14
1.3 Challenges to delivery ........................................................................................................17
1.4 Who needs to be involved? ................................................................................................18
Section 2: Delivering the Plan ...............................................................................................20
2.1 Advancing the use of the 3Rs within the UK ......................................................................20
2.2 Influencing the uptake and adoption of 3Rs approaches globally ......................................26
2.3 Promoting an understanding and awareness about the use of animals where no alternatives exist .......................................................................................................................29
Section 3: Tables ....................................................................................................................30
Glossary ...................................................................................................................................42
Delivering our Commitment to Replace, Reduce and Refine the Use of Animals in Research
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Introduction
The use of animals in scientific research remains a vital
tool in improving our understanding of how biological
systems work both in health and disease. Such use
is crucial for the development of new medicines and
cutting edge medical technologies for both humans
and animals, and for the protection of our environment.
Hence, enabling properly regulated use of animals is
essential to improving the health and lives of humans
and animals and to the safety and sustainability of our
environment.
Our National Health Service is one of the primary
beneficiaries of research and testing using animals –
such as through the licensing of new medicines, the
development of new and safe vaccines and for the
detection and control of infectious diseases.
For example, the development of monoclonal antibody
therapies over the last 20 years has completely
transformed our ability to treat diseases including breast
and other cancers, rheumatoid arthritis and multiple
sclerosis. The development of this technology would not
have been possible without the use of animals both in
developing the fundamental elements of the technology
and in producing the medicines used to treat patients.
Aside from improving quality of life, this research
supports the UK’s world-class research base in
environmental, agricultural, medical and other life
sciences. This in turn will improve the prospects of
patients and animals in the UK benefiting from the
outcomes of research.
It also supports a number of highly skilled jobs
through a strong academic research base and an
attractive regulatory environment. Economically the life
sciences sector contributes over £50bn a year to the
UK economy with agriculture contributing £9bn and
it underpins the UK’s £26bn sector providing us with
healthy and wholesome food.
Underpinning all of this research is a strong
commitment to maintaining a rigorous regulatory system
which ensures that animal research and testing is
carried out only where no practicable alternative exists,
and under controls which keep suffering to a minimum.
This is achieved through robustly applying the principles
of the 3Rs – principles first advocated in the UK over 50
years ago1 – to all research proposals involving the use
of animals.
Implementing the 3Rs requires that, in every research
proposal, animals are replaced with non-animal
alternatives wherever possible; that the number of
animals used is reduced to the minimum needed to
achieve the results sought; and that, for those animals
which must be used, procedures are refined as much
as possible to minimise their suffering.
It is in this context that in 2010, the Government made
a commitment to work to reduce the use of animals
in scientific research. This commitment is not focused
1 Russell & Birch (1959) The Principles of Humane Experimental Technique. http://altweb.jhsph.edu/pubs/books/humane_exp/het-toc
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on baseline numbers which are influenced by a
range of extraneous factors. Instead, it encompasses
replacement, reduction and refinement (the 3Rs) more
broadly, putting them at the heart of a science-led
approach.
The scientific imperative for developing new approaches
to research and development is very strong. Although
the use of animals forms a major part of much scientific
and medical research, success seen in animal studies
has not always translated in the clinic. Many potential
drugs fail due to lack of efficacy in humans or concerns
about their safety. Methods are needed to screen these
failures out as early as possible and to select, with
further research and development, those approaches
most likely to succeed.
Similarly, there are concerns about the utility of animal
studies for testing environmental chemicals. For
example, animals are invariably exposed to much
higher doses than typical human exposures making
interpretation difficult. A number of international science
organisations have called for the development of
mechanism-based assays that are more predictive of
human biology. Increasingly attention has focused on
non-animal technologies for solutions. These include
tissue engineering, stem cells, and mathematical
modelling – areas in which the UK science base is at
the forefront.
There is an opportunity to both minimise the use of
animals and address major challenges faced by society,
such as problems associated with ageing. By tapping
into the UK’s strong science base it is possible to derive
economic benefits from the development of new models
and tools which replace, reduce or refine the use of
animals in research.
In a Written Ministerial Statement on 18 July 20112, we
set out our ambition to deliver the commitment through
such a science-led programme, spearheaded both
by relevant government departments and agencies,
working together where appropriate, and by the National
Centre for the Replacement, Refinement and Reduction
of Animals in Research (NC3Rs), an organisation with a
strong record in promoting the 3Rs in animal research.
In this Delivery Plan we explain that we will remain
strong advocates for this research given its importance
in helping us to combat disease and improve lives and
outcomes for patients and their families. We set out the
detail of how we are delivering against the ambition to
work to reduce the use of animals in research engaging
with the academic sector, health charities and industry
as well as animal welfare bodies.
Our Plan demonstrates how we are taking advantage
of technological developments, including massively
increased computer power and wider scientific
innovation, to provide the perfect environment and
catalyst for scientific change and progress which
will help to reduce the use of animals in research.
2 http://www.publications.parliament.uk/pa/cm201011/cmhansrd/cm110718/wmstext/110718m0001.htm#1107182000388
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Delivering our Commitment to Replace, Reduce and Refine the Use of Animals in Research
Neurons derived from human neural stem cells.Credit Yirui Sun, Wellcome Images
3 https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/32457/11-1429-strategy-for-uk-life-sciences.pdf
It includes actions we are taking directly and
collaboratively across government, and describes how
we are working with our key partner organisation, the
NC3Rs, and others to deliver the commitment. The
Delivery Plan sets out the Government’s three strategic
priorities in delivering the commitment by putting the
3Rs at the heart of a science-led programme:
● advancing the use of the 3Rs within the UK;
● using international leadership to influence the uptake
and adoption of 3Rs approaches globally; and
● promoting an understanding and awareness about
the use of animals where no alternatives exist.
Each of these strategic priorities is considered in detail
in Section 2 of this Delivery Plan.
In our Strategy for UK Life Sciences published in
20113 we set out our aim to make the UK the location
of choice for pioneering research and development
together with investment in the related manufacturing.
This Delivery Plan shows how implementing the 3Rs
makes a real contribution to this strategy, realising
significant benefits for humans, animals and the
environment and sustained economic growth.
A consequence of the commitment in the Coalition
Agreement to work to reduce the use of animals in
scientific research has been, and will continue to be,
to accelerate uptake of the 3Rs both domestically and
internationally. This success is based upon the premise
that the 3Rs provide opportunities for high standards of
animal welfare alongside better science, faster science,
and more cost-effective science. With this in mind, we
have designed a package which is good for patients
and their families, good for science, good for animal
welfare and good for our economic growth. We will
review progress on this Delivery Plan 12 months after
publication and regularly thereafter.
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Delivering our Commitment to Replace, Reduce and Refine the Use of Animals in Research
Section 1Setting the Scene
1.1 The continuing need to use animals in research The Government is clear that there is a continuing need
for properly regulated and ethically conducted research
using animals where the harm caused to the animals
is justified by the potential benefits, and where no
practicable alternative exists. We will continue to make
this case and to improve understanding and awareness
of this issue.
This principle is of fundamental importance to many
sectors including:
● The life sciences sector. Factors such as the
rapid pace of global travel, the looming threat
of widespread anti-microbial resistance, and an
increasingly ageing world population, all present
challenges which impact on both human and animal
health and are importantly reflected in the global
One Health Initiative4. Improved research models
will be required in dealing with the prevalence of
conditions such as pandemic flu, drug-resistant TB,
dementia and the increased burden of obesity and
related conditions such as diabetes, stroke and
heart disease. Animal research will play a vital role
in delivering these challenges.
● The animal welfare sector. The aim to improve
the husbandry and care of farmed, companion,
laboratory, zoo and other managed animals through
approaches which minimise pain, suffering, distress
or lasting harm depends on research, often in those
species.
● The environmental sector. Understanding the
potential impact of chemicals, both naturally
occurring and synthetic, on our environment is
critically important. Whilst many non-animal tests
have been developed in recent years, there remains
a need for animal tests to ensure the safety of
human and wildlife populations.
As a consequence, the UK requires the use of a
significant number of animals in scientific experiments
or procedures each year (see Figure 1) and this Plan
provides the opportunity to set out a more detailed
explanation and justification for their use and the
benefits that result. In 2012, over 4 million procedures
were commenced, significantly lower than the volumes
in the 1970s and early 1980s, but higher than the
figures in the 1990s and 2000s.
In Box 1, we set out some key advances that have
been achieved in recent years as a result of animal
experiments in the UK.
4 http://www.oie.int/fileadmin/Home/eng/Current_Scientific_Issues/docs/pdf/FINAL_CONCEPT_NOTE_Hanoi.pdf
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Delivering our Commitment to Replace, Reduce and Refine the Use of Animals in Research
Box 1: The positive impact of research involving animal experiments
● Zebrafish have been found to
share a highly conserved form of
the key ion channel susceptible
to disrupting QT interval length
(biomarker for cardiac arrhythmia
and sudden death) with humans1.
Scientists have taken advantage
of this similarity to use zebrafish
as an effective model to test the
propensity of drug compounds
to induce cardiac arrhythmias in
human patients.
● Researchers at the MRC
Toxicology Unit at University of Leicester have developed a genetically modified strain of mice to model human
neurodegenerative disease. Study and manipulation of the mouse model has led to the identification of an
orally administered drug compound that can correct the disease pathway and prevent neurodegeneration2.
● Researchers at Cambridge University discovered that deleting the KSR2 gene in transgenic mice caused them
to experience extreme weight gain. Defects in this gene have now been shown to be responsible for abnormal
metabolism in humans offering a potential therapy for obesity and Type 2 diabetes3.
● The use of non-human primates in Parkinson’s Disease research has been invaluable in identifying the
subthalamic nucleus as a surgical target for deep brain stimulation in human patients. This work was initially
carried out at the University of Oxford and has since progressed through human trials to become an effective
treatment for reversing the debilitating tremors experienced by Parkinson’s patients4.
1. Arnaout, R. et al. (2007) Proc. Natl. Acad. Sci. 104(27):11316-21
2. Moreno, J. A. et al. (2013) Sci Transl Med. 5(206):138.
3. Pearce, L. R. et al. (2013) Cell. 155(4):765-77.
4. Parkin, S. et al. (2001) Stereotact. Funct. Neurosurg. 77:68-72.
Figure 1 shows the scale of animal use in research
since 1945. Use has increased steadily and dramatically
since 1945 and peaked around 1970 at a total of over
5.5 million experiments. In 1987, the methodology
for counting the number of animals used in research
changed from counting only experiments to counting
the whole range of scientific procedures. This meant
that the breeding of genetically altered (GA) animals
(mainly mice and fish) was included and this now
accounts for almost half of procedures (48% in 2012).
When the number of GA animals is separately identified
within the totals over the last 20 years (Figure 2), it is
clear that the numbers of animals used in non-breeding
procedures has declined overall from 2.4 million in 1995
to 2.13 million in 2012.
Apart from breeding, the most common use of animals
in research is for fundamental and applied studies in
human medicine5. This can help us to better understand
the pathways and causes of disease and, for example,
bring forward the development of medicines and
vaccines to help save lives and improve outcomes for
5 Includes human dentistry.
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Figure 1. Experiments or procedures commenced each year, 1945–2012.
Figure 2. Animal procedures showing breeding separately since 1995.
0
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All other
Breeding
2012201120102009200820072006200520042003200220012000199919981997199619951994199319921991199019891988
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Experiments
20122010
2005
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Delivering our Commitment to Replace, Reduce and Refine the Use of Animals in Research
Figure 3. Procedures commenced each year on dogs, cats and non-human primates since 1995.
patients. Rodents (such as mice and rats), fish and
birds account for over 98% of all procedures. In 2012,
just over 4,800 procedures involved dogs (0.12%),
mainly beagles, and 3,000 involved non-human
primates (0.07%). In both cases, the majority were used
for safety testing of human medicines. A small number
of procedures involving primates were to aid our
understanding of brain function and disease in humans.
Cats were used in 247 procedures (0.006%), the
majority in nutrition studies for the benefit of cats. The
main fields of research using animals were immunology
(576,000) and cancer research (501,000). Toxicology
accounted for just over 9% of procedures (377,000),
mainly using rodents and fish and none involving the
testing of cosmetics or household products.
As the research potential offered by genetically altered
rodents and fish has increased, so the number used has
risen significantly and this is reflected in total numbers
between 1995 and the present. However, the trend
for many other species – for example dogs, cats and
non-human primates – has generally declined over the
same period (see Figure 3) since much work previously
done in these species can now be done on species of
perceived lower sentience such as mice or fish.
Scientists are required to use the species of the lowest
perceived sentience which is appropriate to their
research. However, this may lead to an increase in
the overall numbers used. For example, neuroscience
studies in a small number of non-human primates may
be replaced by a genetically altered mouse model in
which significantly greater numbers of animals need to
be used.
Box 2 outlines an example in which scientists have
developed a way of replacing one species with another
of perceived lower sentience in their research.
Advances in genetics and understanding the genome
are likely to lead to a continued increase in the use of
genetically modified animals (mainly mice and fish) as
scientists seek to better understand gene functions and
interactions. This research will be essential to finding
potential new targets for treating diseases such as
dementia and type 2 diabetes. It will also underpin the
development of stratified or personalised medicines
0
2,000
4,000
6,000
8,000
catsprimates dogs2012
2011
2010
2009
2008
2007
2006
2005
2004
2003
2002
2001
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1999
1998
1997
1996
1995
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3,000
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which target diseases, such as specific types of cancer,
based on a detailed understanding of a patient’s
genetics and their condition.
Recognising this potentially very significant increase,
the UK is playing a major role in international
programmes (e.g. the International Mouse Phenotyping
Consortium6) which ensure that such genetically altered
strains are characterised and shared globally, hence
maximising their scientific potential whilst minimising the
possibility of duplication.
It is important to note that the annually published
statistics count the number of animals which have been
used in procedures. They do not count the number of
animals which have not needed to be used as a result
of implementing the 3Rs to replace and reduce animal
use. Monitoring success in implementing the 3Rs is
therefore dependent on reviewing case studies. We
6 www.mousephenotype.org
Box 2: An example of replacing non-human primates with transgenic mice
Transgenic mice
have been used
to replace non-
human primates in
oral polio vaccine
safety tests. Polio
vaccine utilises live
attenuated virus
particles and it is essential that each batch of vaccine
is tested to ensure that it is safe and does not revert to
infectious virus on use. Non-human primates possess
virus receptors similar to those found in humans.
However, mice have now been genetically modified
to express human polio receptors. This mouse model
has now been validated and formally adopted by the
European Pharmacopoeia1.
1 http://www.animalresearchforlife.eu/
Replacing%20Primates%20by%20Transgenic%20
mouse%20for%20polio%20vaccine%20testing.pdf
provide a number of such case studies in this Delivery
Plan, and others are published by those who fund this
research such as NC3Rs. Unfortunately no recognised
system exists for assessing the ‘unit of benefit’ to
humans, animals and the environment for each animal
used in research, and how this has improved over time.
A further important absence from the data currently
recorded is a measure of the actual severity which is
experienced. We are committed to correcting this in
2014 to give greater transparency to the public about
what level of suffering really occurs and therefore
improve awareness and understanding about how
animals are used in research and the impacts of it. In
many cases, this will show the severity of procedures to
be mild or less than predicted (e.g. in breeding of many
genetically altered strains). Further, this will also help us
to increasingly focus 3Rs attention on those procedures
which cause the greatest severity.
Nevertheless, it is no simple task to either predict or
contain the number of animals which will be used
in future years. On the one hand global economic
and scientific trends, with demands for even better
medicines and environmental management, may lead
to upward pressure. On the other hand implementing
the 3Rs through new technologies which enable
scientists to use better, faster and cheaper non-animal
approaches will lead to downward pressure.
In this context, a key priority for the Government is to
ensure that we continue to maintain our high standards
through rigorous regulation of the use of animals in
research, and we avoid exporting work overseas to
countries where welfare standards may be lower.
1.2 What the Government is doing to promote the 3Rs1.2.1 Promoting science and innovation in the 3Rs
The UK plays a leading role globally in supporting the
development and adoption of techniques to replace,
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Box 3. The 3Rs in practice
Animal welfare: The NC3Rs champions animal
welfare and high standards in animal research. It
has funded research to improve the assessment and
alleviation of pain in laboratory animals, and to ensure
that rats and mice are killed as humanely as possible at
the end of studies. The Centre reviews all applications
submitted to the major bioscience funding bodies that
involve the use of non-human primates, cats, dogs or
horses, identifying opportunities to further implement
the 3Rs. It also hosts an annual meeting for scientists,
vets and animal care staff who use non-human
primates to discuss welfare issues; recent meetings
have included topics such as training animals to
cooperate with procedures such as blood sampling in
order to minimise any stress they might experience and
the use of imaging technologies.
Training and development: The NC3Rs supports the
training and development of early career scientists so
that the 3Rs are embedded in mindset and practices of
the next generation of research leaders. This includes
a PhD studentship scheme which is dedicated to
the 3Rs and a scheme for early career post-doctoral
scientists (the David Sainsbury fellowship) which
supports the transition to independent researcher. To
date the NC3Rs has funded 37 PhD studentships and
six David Sainsbury fellowships.
Increasingly scientists are using both non-animal (in
vitro) methods and animal-based (in vivo) methods in a
sequential manner. This approach realises the benefits
of the faster and more cost-effective progress which in
vitro methods can often deliver whilst also addressing
the complexity which only an appropriate whole animal
in vivo model can offer.
Recent advances in genetic manipulation and
generation of clinically relevant cell lines for drug testing
and disease modelling have significantly impacted on
the use of animals in research. In pursuing technology
that will help to reduce the number of animals used in
research, scientists in the UK have generated tools that
are invaluable to the study of human development and
disease placing us at the forefront of innovation and
technology internationally.
reduce and refine the use of animals. For example,
the Government has been providing funding to the
NC3Rs since it was established in 2005 and the level
of that funding has significantly increased since 2010
based upon their record of success. The Government’s
research funding bodies (e.g. the Medical Research
Council) have funded major initiatives, often in
partnership with charities such as the Wellcome Trust,
to ensure the UK gives leadership in data sharing
to avoid duplication occurring and to help improve
understanding, for example about the pathways
and causes of disease. Furthermore, a number of
government departments and agencies have, in recent
years, worked collaboratively to develop and validate
new technologies which can replace animal use in
safety testing and help reduce risks to the public, the
environment, pets and farm animals.
Examples of how NC3Rs puts the 3Rs into practice are
set out in Box 3.
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Box 4. Use of induced pluripotent stem cell (iPSC) technology
Progress in the field of induced
pluripotent stem cell (iPSC) biology
has led to the generation of patient
matched cell lines for use in
diagnosis, treatment and study of
disease in vitro.
For example, iPSC lines have been
generated from patients suffering
from congenital liver disease.
They have then been genetically
manipulated to correct the mutation
and effectively cure the disease
in the cells1. These cells are
invaluable for studying the disease
and its effect on human liver cells,
work that in the past could only
have been modelled in animal
systems.
1. Yusa, K. et al. (2011) Nature.
478(7369):391-4
Box 4 describes one way in which cutting edge genetic
manipulation and clinically relevant cell types are being
used to replace animals in research. Reprogramming
mature cells to become pluripotent offers enormous
promise for the future in enabling potential human
therapies to be tested in relevant cells of many types
derived from the target species. The technology has
significant implications for the 3Rs by enabling more
widespread use of human tissues. UK leadership in this
field was recognised by the 2012 Nobel Prize awarded
jointly to Sir John Gurdon and Shinya Yamanaka.
1.2.2 A regulatory framework which enshrines the 3Rs
At the forefront of any decision to use animals in
research is the need for robust evidence to justify
7 https://www.gov.uk/research-and-testing-using-animals
Human induced pluripotent stem cell derived hepatocytes (liver cells) in
vitro. Credit: Richard Gieseck III, University of Cambridge
the use of animals. The UK’s regulatory system7
is geared to prevent animals being used where a
practicable alternative exists and those licensed to
carry out research using animals must ensure that their
proposals comply fully with the principles of the 3Rs.
It also requires a harm-benefit analysis of all research
proposals to ensure that any harm that may be caused
to the animals in terms of suffering, pain and distress is
justified by the expected benefits for humans, animals
or the environment. This analysis is conducted by
Home Office inspectors, all with veterinary or medical
qualifications and special expertise in assessing
research proposals.
In addition, the proposal must have been considered
by the research establishment’s Animal Welfare and
Ethical Review Body (AWERB) to confirm that the
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necessary facilities and staff are available to care for
the animals properly, that the 3Rs have been effectively
implemented in the proposal, and that the work is
considered locally to be acceptable from an ethical
perspective.
During 2012, the UK regulatory system was reviewed
in line with a new European Directive8 with the aim of
both promoting the 3Rs and improving animal welfare
through harmonising standards across Europe.
1.3 Challenges to deliveryWhilst significant efforts are being made by government,
academia, industry, research funders and animal
welfare bodies to advance the 3Rs, there are also
challenges to making rapid progress. Many of these
relate to the need for as yet undiscovered technologies,
but others may relate to conservatism and a risk-
averse approach to adopting change. In developing this
Delivery Plan, we have confronted these challenges
head on to set out ways to address them. We take the
opportunity to set out how research involving animals
can also bring benefits for all of us and we aim to
improve understanding of why this is the case.
A challenge for academia is conservatism on the part
of journal editors and peer-review panels to accept
publications based on non-animal techniques in lieu
of the “traditional” animal models. Publications such
as NC3Rs’ ARRIVE9 Guidelines in 2010, and the now
widespread adoption of these guidelines by a significant
proportion of international journals, have raised
awareness of this issue as well as the need to improve
standards of reporting study design and analysis. This
is impacting standards of peer review and publication
practices internationally.
Within the pharmaceutical industry, licensing of new
medicines such as new treatments for cancer and
heart disease is tightly regulated at both national
and international level by agencies such as the UK
Medicines and Healthcare Products Regulatory
Authority (MHRA) and the European Commission.
However, the need for new medicines is global and, in
order to market their products widely, pharmaceutical
companies must satisfy the testing requirements of all
countries. Hence, even when the UK has accepted a
validated non-animal test, the animal test may still need
to be performed to satisfy another country or region.
Furthermore, if the UK reacts unilaterally in banning the
animal test, the work is likely to move overseas where
welfare standards may be lower.
An international effort to address this dilemma lies
in the International Conference on Harmonisation
of Technical Requirements for Registration of
Pharmaceuticals for Human Use (ICH10) which aims
to reach agreement between Europe, the USA and
Japan for revised pharmaceutical safety testing
guidelines which minimise the use of animals. ICH has
also granted observer status to many other countries
– and these are encouraged to adopt the revised
guidelines once agreed. The International Cooperation
on Harmonisation of Technical Requirements for
8 EU Directive 2010/63 on the protection of animals used for scientific purposes. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2010:276:0033:0079:EN:PDF
9 http://www.nc3rs.org.uk/page.asp?id=135710 www.ich.org
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Registration of Veterinary Medicinal Products (VICH11)
fulfils a similar function for veterinary medicines.
Likewise, testing on animals helps to ensure the safety
of food and environmental chemicals. The evaluation
of the safety of food and environmental chemicals is
undertaken by bodies such as the UK Food Standards
Agency and Health & Safety Executive, the European
Food Safety Authority and the European Chemicals
Agency. At an international level, the Organisation for
Economic Co-operation and Development (OECD)12
sets out the standards which must be satisfied to
give assurances of safety, and to permit international
transport of bulk chemicals. Significant efforts are being
made by OECD (e.g. the Adverse Outcomes Pathways
initiative) to enable sharing of the massive amounts
of data being generated globally following testing on
animals on the toxicity of environmental chemicals, and
to ensure future practices to safeguard our environment
are based upon best practices and minimising the use
of animals as much as possible.
Progress in changing regulatory testing guidelines
can be frustratingly slow since regulators are
understandably averse to adopting changes until they
have absolute confidence that the risks to humans,
animals and the environment are not being increased.
In this Delivery Plan we focus on opportunities
to enhance our influence in both ICH and OECD
discussions and to accelerate changes where they
are supported by sound evidence. We are identifying
key partners (e.g. in the EU, USA, Japan, China and
Brazil) with whom we can work at a diplomatic as
well as a scientific level to catalyse our impact as well
as ensuring that our Plan increases openness and
transparency about how and why animals are used in
research.
1.4 Who needs to be involved?Everyone has a part to play. Government can provide
support and leadership to help to minimise the use of
animals in research and help to make the case for why
animals need to be used when no alternative exists. We
can therefore improve public understanding of why we
need to use those animals.
This must involve all the relevant central government
departments including the Department of Business,
Innovation and Skills (BIS) which supports those who
deliver this research, the Department of Health (DH)
and the Department for Environment, Food & Rural
Affairs (Defra) which both benefit from the outcomes of
this research, and the Home Office which regulates this
research. Agencies and non-ministerial departments
across government also have an important role to play
e.g. Public Health England (PHE), the Food Standards
Agency (FSA), the Health & Safety Executive (HSE),
the Medicines and Healthcare Products Regulation
Agency (MHRA), the Centre for Environment,
Fisheries & Aquaculture Science (Cefas) and the
Veterinary Medicines Directorate (VMD). The Foreign
& Commonwealth Office (FCO) provides important
support in addressing many of the international
challenges.
11 http://www.vichsec.org/en/what-is.htm12 www.oecd.org
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Delivering our Commitment to Replace, Reduce and Refine the Use of Animals in Research
The involvement of our key delivery partner, NC3Rs,
is crucial to this work. The majority of funding for the
NC3Rs currently comes from BIS through ring-fenced
science and research funding allocated by the Medical
Research Council (MRC) and the Biotechnology &
Biological Sciences Research Council (BBSRC). In
addition, other government departments (e.g. Home
Office, and Defra) and the Technology Strategy Board
(TSB), as well as industry and charities, provide funding
either on an on-going basis or for specific projects.
The NC3Rs operates both domestically and
internationally as an independent organisation. It has
established a strong record of effective interactions
with both academia and industry to promote alternative
methods based upon sound scientific evidence. NC3Rs
works with a wide range of partners to develop specific
programmes and schemes. It publishes an annual
report highlighting its successes13 and is very highly
regarded internationally. NC3Rs plays a leading role in
the Government’s delivery of the 3Rs by setting up an
effective framework and changing attitudes.
The MRC and the BBSRC are major public funders of
animal research in the academic sector and play a key
role in providing incentives for researchers to engage
with the 3Rs in the work they fund. Working with the
NC3Rs and other funders such as the Wellcome Trust,
the Research Councils are exploring ways to enable
researchers to make the most of available information
and resources to minimise possible duplication. They
are also developing schemes to increase the collective
knowledge and experience in specific areas of research
and to encourage greater scientific and cross-
disciplinary collaboration.
Animal welfare and alternatives bodies also have a
role to play alongside government in promoting the
3Rs. For example, the RSPCA, through its Rodent
Welfare Group, is working with Home Office inspectors,
scientists and animal care professionals to identify ways
to refine some of the most severe procedures such as
mouse models of human sepsis. FRAME (the Fund for
13 http://www.nc3rs.org.uk/document.asp?id=1899
the Replacement of Animals in Medical Experiments),
with support from Home Office inspectors, has
developed training for young scientists to improve
their skills in experimental design enabling them to
reduce numbers of animals used for the same scientific
outcome.
Oversight of the delivery of the Plan is led jointly by
the Home Office and BIS through a cross-Whitehall
working group with representation from all the relevant
partners. The international work is being monitored and
supported by an Inter-Ministerial Group on International
Animal Welfare.
In the following section, we set out in greater detail the
actions we are taking across three strategic priorities
to address our Coalition Commitment to work towards
reducing the use of animals in research. We also
identify the lead partners for delivery of each of these
actions and the key milestones as indicators of success.
We will review our progress against these milestones a
year after publication.
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Delivering our Commitment to Replace, Reduce and Refine the Use of Animals in Research
Section 2Delivering the Plan
This section of our Delivery Plan describes a wide range
of measures to promote the 3Rs, both within the UK and
internationally, and provide opportunities for researchers
and industry to address the 3Rs in their work. The
actions include encouraging existing programmes and
fostering new, specifically targeted, programmes.
Delivery of the commitment is considered against our
three strategic priorities, putting the 3Rs at the heart of
a science-led programme:
● a domestic programme which focuses on advancing
the use of the 3Rs within the UK;
● an international programme aimed at influencing the
uptake and adoption of 3Rs approaches globally;
and
● a programme aimed at promoting an understanding
and awareness about the use of animals where no
alternatives exist.
We consider each of these strategic priorities in detail
together with specifics of the actions being taken to
ensure their delivery, and some key milestones against
which success will be measured.
2.1 Advancing the use of the 3Rs within the UK The UK has a proud track-record of ensuring that the
use of animals in research is kept to the minimum
whilst also making the case for the benefits that come
from that research – consistent with our position as
a leading innovator in the life sciences. However, the
Government is not complacent and we recognise the
need for scientists to constantly strive to minimise both
the numbers of animals used and the level of pain or
distress experienced by each animal.
Our key objectives are to:
● support the NC3Rs and other funders in delivering
high quality programmes to develop engagement,
uptake and understanding of 3Rs approaches;
● facilitate resource and data sharing and
collaboration across industry and academia;
● ensure the 3Rs are at the heart of all relevant
science including the training of research leaders of
the future;
● enhance the role of Home Office inspectors in
disseminating 3Rs advances;
● enable our targeting of the more severe procedures
through recording ‘actual severity’; and
● more generally, improve awareness and
understanding about why animals need to be used
in research.
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Delivering our Commitment to Replace, Reduce and Refine the Use of Animals in Research
2.1.1. Support the NC3Rs and other funders in delivering high quality programmes to develop engagement, uptake and understanding of 3Rs approaches
The research programme funded by NC3Rs has
already delivered remarkable advances in alternatives
as evidenced by reviews of the research portfolio
and strategic awards (see Box 5). A range of further
NC3Rs led initiatives are described in this Plan,
including innovative approaches such as the CRACK IT
Challenges competition which brings the brain power
of academics and industry together to identify problems
and find innovative solutions which promote the 3Rs.
A new initiative in 2014 will be the launch of an online
resource for scientists to improve their understanding of
good experimental design.
Box 5: The NC3Rs in action
Research: The NC3Rs1 has invested £35.1 million
for research to support advances in the 3Rs across
the biosciences. Over half of this is for research to
replace animal use. NC3Rs-funded researchers have
provided opportunities to minimise animal use in
areas such as cancer, epilepsy and multiple sclerosis
research and toxicity testing. This involves using
the latest technologies including tissue engineering,
microfluidics and mathematical modelling. In 2011,
the Centre launched the first challenge-led research
competition, CRACK IT Challenges, which is designed
to support economic growth and the commercialisation
of 3Rs technologies by bringing together scientists
from universities, small and medium-sized enterprises
and major industries to tackle problems which if solved
have 3Rs and business benefits.
Collaborations: The NC3Rs works collaboratively
with over 30 companies in the pharmaceutical,
biotechnology, chemical, agrochemical and consumer
product sectors, nationally and internationally. This
has resulted in changes to international regulations,
for example, the removal of the requirement to do
single dose acute toxicity testing in animals. The
Centre also works collaboratively with international
regulatory agencies. This includes two initiatives jointly
led by the NC3Rs and MHRA on reducing the use of
‘recovery’ animals in pharmaceutical development
and using human tissue instead of animals for safety
pharmacology studies.
1 http://www.nc3rs.org.uk/
The Government recognises that its funding for
alternatives to research is a very small proportion
of the overall funding it provides to the Research
Councils which also fund animal experiments.
However, it has demonstrated its commitment to the
NC3Rs by increasing funding at a time when the fiscal
consolidation has required substantial funding cuts
to many other areas of government. In 2010/11 the
NC3Rs received £5.3 million from government (MRC,
BBSRC, Home Office) and this will increase to just over
£8 million in 2014/15 (MRC, BBSRC, EPSRC, Home
Office, Defra).
Other funders and agencies commissioning or carrying
out research in animals also have a role to play in
supporting 3Rs research. For example, BBSRC,
working with the NC3Rs, has highlighted a call for
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proposals on animal welfare measures and assessment
(Action 1.9). Sixteen projects have been funded and
BBSRC is planning a series of events to disseminate
results throughout the course of the programme.
Funders now routinely use online tools to capture
the outputs of the research they fund. This gives
researchers an opportunity to show the benefits
and impacts of their research such as publications,
collaborations, patents and industrial funding. The
Research Councils have undertaken to add to these
tools to capture data not only on implementation of
the 3Rs in research but also to allow researchers to
report 3Rs impacts of their research (Action 1.7). Over
time, such measures will act as a powerful means to
change behaviour and culture, even further encouraging
researchers to consider the 3Rs in the work they
do. This will also provide an additional resource for
understanding the extent of 3Rs innovation in research.
Relevant funding peer review processes include an
assessment of the justification for animal use and
an assessment of whether the numbers of animals
proposed will provide robust experimental results.
The Research Councils, working with the NC3Rs, are
currently reviewing, updating and harmonising their
requirements for this justification. This is with the aim
of ensuring that every research programme and project
proposal receives effective scrutiny before it is funded
and that opportunities to implement scientific advances
to replace, reduce or refine animal use are not being
missed (Action 1.8).
The Technology Strategy Board (TSB) considers
new pipeline technologies as part of its Emerging
Technologies and Industries Strategy. Following a series
of workshops held jointly in 2013 with the NC3Rs, TSB
has selected “non-animal technologies” for feasibility
study competitions opening in first quarter 2014
(Action 1.12). This demonstrates the real potential for
technological development in this area in the UK.
2.1.2 Encourage government departments and agencies to place the 3Rs at the heart of their work
Many government departments and agencies have
responsibility for research involving animals. We
consider the role of regulators in Section 2.1.5. In this
section we consider those who commission or perform
such research and play an important role in promoting
the 3Rs.
Defra has a number of agencies performing research
to address the department’s responsibilities for animal
(and human) health and environmental safety.
For example, the Centre for Environment, Fisheries &
Aquaculture Science (Cefas) has moved away from
death as an end-point in fish research, has developed
protocols to reduce the number of fish used in routine
testing across Europe, is actively researching methods
to enhance fish welfare and was the first laboratory
in Europe to completely eradicate the use of mice in
testing the safety of shellfish (in collaboration with the
Food Standards Agency and the Home Office – see
Box 6). It is also notable that a large number of fish are
immobilised simply for tagging. This has been counted
as a procedure in the Home Office annual statistics
although the tagged fish continue to function, swim and
migrate normally.
The Animal Health & Veterinary Laboratories Agency
(AHVLA) has made great strides over the years in
the use of non-animal alternatives and in refining
end-points where animals must be used. Some of the
reductions involve areas for which there is a statutory
responsibility such as diagnostic tests for avian flu and
rabies. Co-ordinated effort across Europe also reduces
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Delivering our Commitment to Replace, Reduce and Refine the Use of Animals in Research
Box 6. How government departments, agencies and public bodies are promoting the 3Rs in their work
● The detection of paralytic and diarrhetic toxins in
commercially harvested shellfish has traditionally
used severe bioassays in mice involving significant
suffering. A collaborative effort between Defra
(Cefas), FSA and Home Office (ASRU) inspectors
has led to the successful optimisation and
implementation of two non-animal alternative tests.
Over 8,000 mice were used in 2007. In 2012,
fewer than 50 mice were used in the traditional
animal test compared with a projected 13,000
mice which would otherwise have been needed to
ensure human safety. The animal assays were fully
replaced in May 2012 and animals are no longer
used for shellfish safety testing. The alternative
tests are now being adopted more widely across
Europe.
● Where a new vertebrate animal test is required for
the assessment of the potential reproductive toxicity
of an industrial chemical (e.g. to assess its possible
impact on fertility), the traditional “gold standard”
test involves the study of rats over two generations,
as described in OECD Test Guideline 4161. A new
test has been developed – the Extended One
Generation Reproductive Toxicity Study (EOGRTS),
which offers a much more flexible study design that
can generate sufficient information for regulatory
purposes without the mandatory production of the
second generation. The EOGRTS uses about half
the number of animals (reducing from 2,600 to
1,400 per test) compared with the two-generation
study. The EOGRTS was adopted by the OECD
in 2009. Subsequently, Defra and the HSE (the
UK Competent Authority for REACH), along with
authorities from other key Member States, have
successfully promoted its adoption in the EU.
Adoption of the EOGRTS in the REACH Test
Methods Regulation is now anticipated in mid 2014.
1 http://www.oecd.org/env/ehs/testing/
the potential for duplication (e.g. recently in researching
Schmallenberg virus) although this may often increase
the number of animals used in the UK on behalf of
Europe.
The Food & Environment Research Agency (Fera)
carries out much of its work using wild animals and
carefully reviews all research proposals to ensure the
principles of the 3Rs are being effectively applied. Fera
also works with the Universities Federation for Animal
Welfare (UFAW) and the RSPCA to provide expert
training and guidance for those wishing to work with wild
mammals or birds to ensure best practice at all times.
Other examples of government departments applying
the 3Rs include Public Health England (PHE) which
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In fact all government departments, agencies and public
bodies which commission research which involves the
use of animals, or which are responsible for regulations
which require animal testing, have a duty to consider
the 3Rs in their work (Action 1.13) along with supporting
others in setting out clearly the benefits the research
can bring and helping to improve understanding and
awareness of the issue.
2.1.3 Facilitate data sharing and collaboration across industry and academia
The MRC and BBSRC are the major public funders of
animal research in the academic sector and have a key
role to play in influencing the culture of researchers who
use animals and in providing incentives for researchers
to engage with the 3Rs.
Working with the NC3Rs, Research Councils are
looking for ways to increase resource sharing (Action
1.2) so that individual research programmes can
make the most of available resources. These may be
has recognised that the detection, tracking and
management of outbreaks of disease is an area
where innovation using whole genome sequencing of
pathogens can replace the use of techniques which
have previously required generating antibodies in
rabbits (Action 1.11). An initiative is underway to explore
this further with the potential to significantly reduce the
use of animals in this area.
outcomes of research, animals, data or other resources.
This will enable researchers to make the most of
available information and will help to prevent duplication
and increase collective knowledge and experience in
specific areas of research. It will also provide greater
efficiencies in research as well as encouraging cross-
disciplinary collaboration.
The UK makes a major contribution to global mouse
phenotyping and the free exchange of information
about genetically altered strains. This is achieved
through programmes such as the International Mouse
Phenotyping Consortium (IMPC) and the Knockout
Mouse Program (KOMP2) and means that duplication
of work which would otherwise involve much greater
numbers of animals is avoided (Action 1.2).
2.1.4 Ensure the 3Rs are at the heart of all relevant science including the training of research leaders of the future
To ensure the 3Rs are at the heart of animal-based
science, the Research Councils are issuing updated
requirements for all funding applications which involve
the use of animals. This is to ensure that every research
proposal receives effective scrutiny before it is funded
and that opportunities to implement 3Rs advances
are not missed. Furthermore, a strategy to embed the
3Rs in the training and development of scientists from
the start of their careers is driven through the NC3Rs-
funded PhD studentship scheme (Action 1.3).
2.1.5 Enhance the role of Home Office inspectors and other regulators in disseminating 3Rs advances within a robust regulatory framework
As regulators of animal research, the Home Office
Animals in Science Regulation Unit (ASRU) plays a
central role in dissemination of best practice. The 2012
amendments to the Animals (Scientific Procedures) Act
(ASPA), implemented by the Government to transpose
the new Directive (2010/63/EU), have promotion
of the 3Rs at their core. Home Office inspectors, in
reviewing applications for projects, encourage and
require 3Rs approaches to be robustly implemented
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Delivering our Commitment to Replace, Reduce and Refine the Use of Animals in Research
(see Box 7). In this, they are particularly effective in
relation to refinement and reduction. However, given
the complexity of science, access to sound reference
material regarding replacement options is not always
readily available.
A number of approaches are being pursued to address
this, including greater emphasis in the relevant
Guidance on the Operation of the Act. Applicants are left
in no doubt about their absolute responsibility to ensure
they have rigorously explored all options to implement
the 3Rs in their application. Means of more effectively
acquiring and disseminating information, particularly on
replacement options, are also being explored (Action
1.4).
The EU Directive provides an opportunity to require
companies in the UK to take positive action to develop
and validate alternative tests, particularly in relation to
batch testing of biological products such as vaccines
and toxins with significant benefits to human health for
example. In relation to novel products, both MHRA in
relation to human health and VMD in relation to animal
health are robustly pursuing this by requiring applicants
for new Marketing Authorisations to demonstrate the
absence of a suitable non-animal release test before an
authorisation based on an animal test will be approved.
Further, with existing biological products where a
non-animal test is known to have been validated and
accepted for one manufacturer’s product, we will pursue
other manufacturers to validate a non-animal test for
their similar product. This includes waiving the fees
normally charged for varying a Marketing Authorisation
where the change represents implementation of the
3Rs.
The VMD is in the final stages of completing a project
which has involved reviewing all veterinary vaccines
produced in the UK to identify where animals are still
being used for batch release and whether any tests
are unnecessary. As a result of these measures, it is
estimated that about 5,000 fewer animals will be used
each year in testing for an equivalent number of batches
released.
Where veterinary medicines are used in food-producing
animals it is important to establish potential harmful
effects in humans who may consume the meat, milk,
eggs, etc. and also to understand how the medicines
are metabolised and depleted from the animal tissues
so that safe withdrawal periods can be set. This
requires the use of animals, mainly target species,
but by implementing 3Rs approaches we ensure the
numbers involved are minimised.
Nevertheless, it is accepted that biological products
vary significantly according to the production process
Box 7. Refinement opportunities in batch testing of biologicals
● Assessing the safety and efficacy of each batch
of Botulinum toxin involves a very severe test in
mice in which animals become paralysed and will
die if not humanely killed. One manufacturer has
validated an alternative test to replace at least
some of the animal use for their particular product.
The Home Office and MHRA are actively pressing
other manufacturers to do likewise. Given this
may take some time to complete, Home Office
inspectors have meanwhile required refinement
of the mouse test to reduce the severity as far as
possible. For example, mice are checked very
regularly, at least once every hour, throughout the
day and night to ensure they are observed as soon
as they show clinical signs and humanely killed
whenever possible. Collaboration such as this
between the Home Office, MHRA, manufacturers
and their testing laboratories is very important. We
are also engaging with the European Commission
and internationally (e.g. with US FDA) to share best
practice more widely.
● Since 2007, a similar approach taken by VMD has
led to a 50% decrease in the number of animals
used per batch in testing the safety and efficacy of
clostridial vaccines intended for use in horses.
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and read across from one to another cannot be
assumed. Further, where the product tested in this
country is destined for global markets, we realise that
the Marketing Authorisation in each of those countries
needs to be amended before the animal test becomes
redundant.
This is a significant problem which risks exporting
tests, many of which are severe, to overseas countries
where welfare standards may be lower. We are actively
pursuing this dilemma with the European Commission
to seek a way forward which does not simply export the
problem elsewhere.
2.1.6 Enable our targeting of the more severe procedures through recording ‘actual severity’
We are committed to implementing a robust system
of reporting actual severity of procedures on animals
from January 2014. To ensure the data collected are
as reliable as possible, Home Office inspectors have
conducted a pilot study during 2013 which will form the
basis of guidance on categorising actual severity as
sub-threshold, mild, moderate or severe. These data
will provide clarity on the burden of harm, including
Human neural stem cells.Credit Yirui Sun, Wellcome Images
cumulative harm, to animals used in research and,
over time, will measure the effectiveness of refinement
efforts, particularly for those procedures at the most
severe end of the spectrum (Actions 1.5 and 1.6).
2.2 Influencing the uptake and adoption of 3Rs approaches globallyAnimal experimentation in the UK constitutes only a
relatively small proportion of global use of animals in
research and we want to share some of the benefits of
the progress we have made in the UK. Furthermore,
much regulatory testing involving animals will only be
replaced with non-animal techniques when the latter
is accepted globally (see Section1, Challenges to
delivery).
The Government is therefore committed to spread best
practice and use its influence overseas to work with
other countries and international regulators to replace,
reduce, and refine the use of animals, particularly in
regulatory testing and also to improve understanding
about why animals are used in research. This will
benefit the UK economy as well as enhance animal
welfare.
Our key objectives are to:
● support the NC3Rs’ international initiatives;
● engage with other countries, especially through
ICH and OECD, to promote the harmonisation of
global regulatory standards which use alternatives
wherever possible;
● provide an evidence base for where changes would
be beneficial to international regulations which
require animal use; and
● work to end unnecessary animal testing for
cosmetics globally.
Through this programme, we will further develop the
UK’s position in influencing the international uptake
of 3Rs approaches and provide an opportunity to
contribute to a more harmonised global framework for
the benefit of animal welfare and UK competitiveness.
The programme will:
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Delivering our Commitment to Replace, Reduce and Refine the Use of Animals in Research
● enable companies with high ethical standards to
trade in growing markets that currently require the
use of questionable animal tests in order to market
their products; and
● help support the UK’s Life Sciences industry, an
important component of the Government’s Industrial
Strategy, by harmonising international regulatory
testing requirements.
In Table 2 we describe the actions we will be taking in
this international programme.
2.2.1 Supporting the NC3Rs’ international initiatives
The NC3Rs is working to ensure the international
adoption of best practice in a variety of areas. These
include:
● reducing the use of animals in safety pharmacology
studies by using human tissues, working with 25
pharmaceutical companies, contract research
organisations, academics and regulators from the
UK, Europe and the USA;
● minimising the use of recovery animals (rats,
dogs or non-human primates) in pharmaceutical
development; and
● refining inhalation toxicology methods to make the
‘fixed concentration procedure’ more widely adopted
through objective scoring.
2.2.2 Engage with other countries, especially through ICH and OECD, to promote the harmonisation of global regulatory standards which use alternatives wherever possible
The work at an international level presents an
opportunity to contribute to a more harmonised global
framework for the benefit of UK competitiveness
alongside demonstrating the UK’s commitment to
reducing the use of animals in research and providing
global leadership. This is a key issue for the UK and the
Life Sciences sector and is an important component of
Box 8. An example of overseas engagement – China
Working with FCO colleagues, we will support a
Chinese initiative to develop standards for research
animal welfare and ethical use. Through funding an
international seminar on this topic, we will help drive
the endorsement of these standards as national
regulations. Building on this collaboration, we will
further work with Chinese regulators (e.g. CFDA) to
develop a science-led strategy and action plan to
cease unnecessary animal testing of cosmetics and
to harmonise safety testing of medicines in animals
(Actions 2.4 and 2.5).
14 The Government is developing long-term strategic partnerships with industry sectors where we can have the most impact on growth.
the Government’s Industrial Strategy14. Action is geared
towards supporting and encouraging economic growth.
Harmonisation of international regulatory requirements
and the adoption of better alternatives will support
this. The UK must ensure that it enters international
negotiations in good faith with the intention of accepting
the outcome if at all possible, to maintain credibility and
commitment to reduce gold plating.
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With increasing globalisation of both commerce and
science comes a need for greater harmonisation of
approaches. Actions 2.1 to 2.5 are designed to address
these through a number of approaches. For example,
the work of the NC3Rs together with the MHRA
(Action 2.1) will help to solve specific problems in
regulatory science and are already providing a focus for
collaboration in these issues amongst global industries.
The UK can also use its global standing both as a
leader in the development and implementation of the
3Rs and as a nation at the forefront of innovation in
this area to influence international regulators to early
adoption of scientifically proven 3Rs alternatives for
regulatory testing. Actions in 2.3 set out just a few
examples that we are working on at present.
2.2.3 Working to end unnecessary animal testing for cosmetics globally
Testing of cosmetics on animals is an area of great
public concern (Action 2.4). In the UK, the testing of
cosmetics in animals has not been permitted since
1998. Work is underway to develop an international
strategy towards the eventual eradication of
unnecessary animal testing of cosmetics products,
adopting a science-led approach.
The European Union, via the seventh amendment to the
Cosmetics Directive, brought in a phased approach to
banning animal testing. Initially, a ban on the testing of
finished cosmetics in animals was implemented in 2004.
This was followed by a ban on the testing of ingredients
or combinations of ingredients in 2009 together with
a partial marketing ban which applied to all except
tests for the most complex human health effects (e.g.
carcinogenicity tests) where alternatives were not
available. The marketing ban was completed in 2013.
There may remain a requirement for some animal test
data to demonstrate safety of cosmetic ingredients in
the absence of validated alternative tests. But in most
cases historic animal test data, or data from tests
undertaken for non-cosmetic purposes, can be used to
assure safety.
This compares with other markets across the globe
which may either require animal testing (e.g. China)
or may accept data from animal testing as evidence of
human safety (e.g. USA). Hence, animal tests are either
explicit or implicit in the legislation.
Ethical manufacturers within the European cosmetics
industry believe that animal tests on finished
cosmetics are unnecessary because safety can be
definitively demonstrated by other means. Making
use of connections offered through the Foreign &
Commonwealth Office (FCO), we propose to engage
with the relevant overseas regulators and scientists to
promote strategies which will enable and encourage
them to move away from unnecessary animal testing.
We believe this has potential benefit for all concerned.
For example, our proposed initiative in China (Action
2.5 and Box 8) will not only open up this market for UK
and European companies but will also open up UK and
European markets to Chinese companies. At the end of
29
Delivering our Commitment to Replace, Reduce and Refine the Use of Animals in Research
the day, consumers will benefit from a diverse range of
safe cosmetics which have not undergone unnecessary
animal testing.
2.3 Promoting an understanding and awareness about the use of animals where no alternatives existWe are committed to a culture of openness and
transparency to help improve public understanding of
the research which is carried out as well as the many
ways in which alternatives are used. Also to explain
some of the real public and animal health benefits that
have resulted from the research which has been carried
out on animals.
Openness is crucial to ensure that we signal to global
industry and academia that we are a great destination
for high quality life sciences research. We will promote
that research in an environment which both supports
openness about the need for the use of animals and the
benefits that can result, e.g. from cholesterol lowering
drugs to rabies vaccines for family pets, but which also
nurtures a culture of innovation to look for new and
improved ways of tackling 3Rs questions.
We believe the research community and the public will
benefit from knowing more about the actual severity,
in terms of pain or distress, experienced by research
animals and may have fears or misconceptions allayed.
We therefore welcome the new European requirement
to record, at the end of each procedure, the category
(sub-threshold, mild, moderate or severe) of severity
actually experienced by each animal. During 2013 we
have conducted pilot record collection to ensure the
quality of reporting is as accurate and consistent as
possible and we will publish guidance. Not only will
actual severity reporting provide greater transparency
it will also enable us to identify where the greatest
severity occurs and to focus refinement initiatives
towards those procedures (Action 3.2).
We have welcomed the work that a coalition of industry,
academia, health charities and research funding
bodies is leading on a Concordat on Openness15, about
animal research. This initiative also aims to improve
understanding and awareness about the ways in which
animals are used in scientific, medical and veterinary
research in the UK (Action 3.3).
The Home Office is delivering on its commitment to
review section 24 of ASPA, the so-called ‘Confidentiality
Clause’. Multi-stakeholder workshops are being held to
seek ideas of how the licensing process can be made
more open and transparent. At the same time, personal
safety must be assured by safeguarding identities of
people and places, and intellectual property must be
protected to ensure that scientists’ greatest assets,
their ideas, are not plagiarised. This is a complex piece
of policy being developed as part of delivering this
Coalition Commitment (Action 3.4).
Through all these initiatives, we want to improve public
understanding of the context of animal research and
the licensing framework and to engage the public
and the research sector in a transparent conversation
around the use of animals in research. A mechanism for
gauging the success of all these and other approaches
will be monitored through the public response to
surveys such as Public Attitudes Survey 2014 (Action
3.1).
15 http://www.understandinganimalresearch.org.uk/policy/concordat-on-openness-on-animal-research
30
Delivering our Commitment to Replace, Reduce and Refine the Use of Animals in Research
Section 3Tables
In Section 2 of our Delivery Plan we have described a
wide range of measures to promote the 3Rs, both within
the UK and internationally and provide opportunities
for researchers and industry to address the 3Rs in
their work. The actions include encouraging existing
programmes and fostering new, specifically targeted,
programmes.
In this section we describe each of the actions in
greater detail in a series of three tables. Each table
considers delivery against one of our three strategic
priorities, putting the 3Rs at the heart of a science-led
programme:
● Strategic Priority 1 – a domestic programme which
focuses on advancing the use of the 3Rs within the
UK;
● Strategic Priority 2 – an international programme
aimed at influencing the uptake and adoption of 3Rs
approaches globally; and
● Strategic Priority 3 – a programme aimed at
promoting an understanding and awareness about
the use of animals where no alternatives exist.
In each table, we consider specific actions which are
either underway or proposed. We indicate the lead
organisations for each action, and provide some key
milestones against which success will be measured.
Finally, we indicate our expected timelines for each of
the milestones or, where appropriate, we indicate where
work is ongoing.
We will review our progress against these milestones a
year after publication of this Delivery Plan.
31
Delivering our Commitment to Replace, Reduce and Refine the Use of Animals in Research
Title
/lead
org
anis
atio
n(s)
Act
ions
(und
erw
ay o
r pro
pose
d)M
easu
res
of s
ucce
ss a
nd k
ey m
ilest
ones
Tim
elin
es1.
1 N
atio
nal C
entr
e fo
r the
R
epla
cem
ent,
Ref
inem
ent
and
Red
uctio
n of
Ani
mal
s in
Res
earc
h pr
ogra
mm
es
(NC
3Rs)
1) P
ublic
atio
n of
the
seco
nd re
view
of t
he N
C3R
s re
sear
ch
portf
olio
by
Nov
embe
r 201
3.- R
ecei
ved
posi
tivel
y by
sta
keho
lder
s an
d se
ctor
.- E
nhan
ced
unde
rsta
ndin
g by
sta
keho
lder
s an
d pu
blic
of h
igh
qual
ity re
sear
ch fu
nded
by
the
NC
3Rs
and
the
anim
al w
elfa
re,
scie
ntifi
c an
d so
ciet
al b
enef
its o
f thi
s.
Pub
lishe
d N
ovem
ber 2
013.
2) L
aunc
h of
the
NC
3Rs
Exp
erim
enta
l Des
ign
Ass
ista
nt o
nlin
e re
sour
ce.
Ear
ly u
ptak
e an
d us
e by
rese
arch
com
mun
ity a
nd im
prov
ed
unde
rsta
ndin
g of
the
3Rs
bene
fits
to g
ood
expe
rimen
tal d
esig
n.S
prin
g 20
14.
3) C
RA
CK
IT: T
he 2
013
CR
AC
K IT
Cha
lleng
es c
ompe
titio
n co
nsis
ts o
f fiv
e C
halle
nges
iden
tifie
d jo
intly
by
the
NC
3Rs
and
indu
stry
spo
nsor
s w
ho p
rovi
de in
-kin
d co
ntrib
utio
ns in
clud
ing
data
, acc
ess
to c
ompo
unds
, val
idat
ion
stud
ies,
etc
. CR
AC
K IT
C
halle
nges
is a
mile
ston
e-dr
iven
fund
ing
com
petit
ion
from
the
NC
3Rs
whi
ch is
des
igne
d to
(i) m
inim
ise
the
use
of a
nim
als
in re
sear
ch; a
nd (i
i) su
ppor
t the
dev
elop
men
t of m
arke
tabl
e pr
oduc
ts a
nd/o
r im
prov
ed b
usin
ess
proc
esse
s. T
he to
tal b
udge
t fo
r the
201
3 ro
und
of C
RA
CK
IT C
halle
nges
is a
ppro
xim
atel
y £7
M.
Con
tract
s aw
arde
d to
add
ress
the
chal
leng
es.
The
win
ners
of
the
com
petit
ion
will
be
anno
unce
d in
Ja
nuar
y 20
14.
4) S
trate
gic
awar
d: Im
agin
g te
chno
logy
dev
elop
men
t for
the
3Rs
– th
e N
C3R
s ha
ve re
cent
ly a
nnou
nced
a s
trate
gic
fund
ing
call
to s
uppo
rt hi
gh-q
ualit
y re
sear
ch p
ropo
sals
to a
ddre
ss
genu
ine
tech
nolo
gica
l cha
lleng
es in
pre
clin
ical
imag
ing
whi
ch if
so
lved
wou
ld a
dvan
ce s
cien
ce a
nd th
e 3R
s. T
he to
tal b
udge
t for
th
is s
trate
gic
call
is £
1M.
Awar
ds m
ade.
S
ucce
ssfu
l ap
plic
ants
will
be
ann
ounc
ed in
M
arch
201
4.
5) D
isea
se m
odel
s –
the
NC
3Rs
are
deve
lopi
ng a
pro
gram
me
of w
ork,
bas
ed o
n pr
evio
us e
xper
ienc
e, fo
cusi
ng o
n di
seas
e m
odel
s an
d ef
ficac
y te
stin
g. T
his
incl
udes
dis
ease
are
as s
uch
as a
sthm
a, e
pile
psy
and
pain
, and
they
are
wor
king
with
the
AB
PI t
o se
cure
fund
ing
to le
ad o
n th
is. A
n in
itial
prio
rity
is
canc
er m
odel
s.
Eng
agin
g an
d bu
ildin
g re
latio
nshi
ps w
ith th
e ca
ncer
rese
arch
co
mm
unity
in a
pply
ing
the
3Rs
to th
eir r
esea
rch.
Wor
ksho
p to
brin
g th
e ca
ncer
rese
arch
co
mm
unity
to
geth
er –
Spr
ing
2014
.
1.2
Impr
oved
reso
urce
sh
arin
g in
clud
ing
outc
omes
of r
esea
rch,
re
sour
ces,
ani
mal
s an
d da
ta
(NC
3Rs
with
MR
C a
nd
BB
SRC
)
Exa
mpl
es o
f ong
oing
wor
k in
clud
e:- R
ecen
tly la
unch
ed N
C3R
s in
frast
ruct
ure
for I
mpa
ct (I
fI)
sche
me.
- Sha
red
Age
ing
Res
earc
h M
odel
s (S
hAR
M –
Bio
repo
sito
ry o
f ag
ed m
ouse
tiss
ues)
- Ava
ilabi
lity
of N
on H
uman
Prim
ate
tissu
e fro
m C
entre
for
Mac
aque
s (C
FM).
- Enh
ance
d ar
chiv
ing
of a
nim
al m
odel
s in
aca
dem
ia.
- Coo
rdin
ated
mou
se p
heno
typi
ng o
f gen
etic
ally
alte
red
anim
als
(IMP
C).
- The
NC
3Rs
and
fund
ers
are
cons
ider
ing
way
s to
enh
ance
da
ta s
harin
g an
d pu
blic
atio
n of
neg
ativ
e re
sults
.
Four
Infra
stru
ctur
e fo
r Im
pact
pro
ject
s aw
arde
d to
talli
ng £
1.3M
.O
ngoi
ng.
Stra
tegi
c Pr
iorit
y 1:
Adv
anci
ng th
e us
e of
the
3Rs
by p
uttin
g th
em a
t the
hea
rt o
f sci
ence
-led
prog
ram
mes
32
Da
elivering our Commitment to Replace, Reduce nd Refine the Use of Animals in Research
Title
/lead
org
anis
atio
n(s)
Act
ions
(und
erw
ay o
r pro
pose
d)M
easu
res
of s
ucce
ss a
nd k
ey m
ilest
ones
Tim
elin
es1.
3 Po
stgr
adua
te 3
Rs
trai
ning
(N
C3R
s)P
hD s
tude
ntsh
ip s
chem
e as
par
t of t
he N
C3R
s st
rate
gy to
em
bed
the
3Rs
in th
e tra
inin
g an
d de
velo
pmen
t of s
cien
tists
fro
m th
e st
art o
f the
ir ca
reer
s. T
o da
te 3
7 aw
ards
in to
tal h
ave
been
mad
e.
Impr
oved
trai
ning
on
proj
ect d
esig
n fo
r PhD
st
uden
ts.
Ong
oing
.
1.4
Incr
ease
the
impa
ct o
f Hom
e O
ffice
in
spec
tors
and
oth
er re
gula
tors
in th
e di
ssem
inat
ion
of 3
Rs
adva
nces
and
ad
vise
abo
ut im
plem
enta
tion
(HO
and
MH
RA
)
Enh
ance
d di
ssem
inat
ion
of th
e 3R
s th
roug
h co
ntin
ued
deve
lopm
ent o
f exp
ert k
now
ledg
e ne
twor
ks (i
nter
nal H
O
Insp
ecto
rate
act
iviti
es w
orki
ng w
ith o
ther
s e.
g. N
C3R
s) a
nd
exte
rnal
ly w
ith li
cens
ees
thro
ugh:
- pub
licat
ion
of G
uida
nce
on th
e op
erat
ion
of th
e A
ct w
ith
incr
ease
d em
phas
is o
n 3R
s an
d ha
rm-b
enef
it as
sess
men
t;- o
utre
ach
activ
ities
atte
ndin
g an
d sp
eaki
ng a
t mee
tings
and
co
nfer
ence
s; a
nd- r
egul
ar d
iscu
ssio
ns w
ith n
ew a
nd e
xist
ing
licen
sees
.
i) G
uida
nce
to n
ew re
gula
tions
pub
lishe
d in
clud
ing
sign
ifica
nt m
ater
ial o
n 3R
s an
d ha
rm-b
enef
it as
sess
men
t.ii)
Insp
ecto
rate
hav
e fo
rmal
ised
a s
trate
gy
for i
nter
nal k
now
ledg
e tra
nsfe
r.iii
) Ins
pect
orat
e ha
ve fo
rmal
ised
a s
trate
gy
for d
isse
min
atio
n of
3R
s in
form
atio
n an
d im
plem
enta
tion
with
lice
nsee
s.iv
) Con
tinua
tion
of C
ontin
uous
Pro
fess
iona
l D
evel
opm
ent a
ctiv
ities
and
net
wor
king
with
re
leva
nt s
take
hold
ers.
i) D
ecem
ber 2
013.
ii) J
uly
2014
.
iii) J
uly
2014
.
iv) O
ngoi
ng.
Incr
ease
d re
quire
men
t to
appl
ican
ts fo
r new
Mar
ketin
g A
utho
risat
ions
to d
emon
stra
te a
bsen
ce o
f a s
uita
ble
non-
anim
al te
st b
efor
e an
aut
horis
atio
n ba
sed
on a
n an
imal
te
st w
ill b
e ap
prov
ed.
Wor
king
with
the
Hom
e O
ffice
, M
HR
A to
pur
sue
man
ufac
ture
rs w
ith e
xist
ing
Mar
ketin
g A
utho
risat
ions
to v
alid
ate
non-
anim
al te
sts
for t
heir
prod
uct,
parti
cula
rly w
here
the
anim
al te
st is
sev
ere,
or w
here
ano
ther
m
anuf
actu
rer o
f a s
imila
r pro
duct
has
val
idat
ed a
non
-ani
mal
te
st.
i) N
ew M
arke
ting
Aut
horis
atio
ns b
ased
on
non-
anim
al te
sts
bein
g ap
prov
ed.
ii)W
aivi
ng o
f app
licat
ion
fee
by c
lass
ifyin
g su
ch a
cha
nge
as a
Typ
e 1
varia
tion
to th
e M
arke
ting
Aut
horis
atio
n.
iii) N
on-a
nim
al te
sts
for e
xist
ing
Mar
ketin
g A
utho
risat
ions
bei
ng s
ubm
itted
.
Com
men
ced
in e
arne
st
in 2
010
and
on-g
oing
.
33
Delivering our Commitment to Replace, Reduce and Refine the Use of Animals in Research
Title
/lead
org
anis
atio
n(s)
Act
ions
(und
erw
ay o
r pro
pose
d)M
easu
res
of s
ucce
ss a
nd k
ey
mile
ston
esTi
mel
ines
1.5
Ref
inem
ent o
f mod
els
(RSP
CA
with
HO
)
(Cef
as w
ith N
C3R
s)
Wor
k to
refin
e th
e m
ost s
ever
e m
odel
s to
avo
id o
r red
uce
anim
al s
uffe
ring.
Mod
els
to b
e co
nsid
ered
incl
ude:
- Exp
erim
enta
l Aut
oim
mun
e E
ncep
halo
mye
litis
(EA
E);
- Sei
zure
s;- R
heum
atoi
d ar
thrit
is; a
nd
- Sep
sis.
- Rep
orts
on
each
of t
he s
elec
ted
topi
cs
prep
ared
and
pub
lishe
d.- R
ecom
men
datio
ns p
rom
ulga
ted.
i) E
AE
repo
rt pu
blis
hed
late
201
2.ii)
Sei
zure
s re
port
publ
ishe
d 20
13.
iii) R
hem
atoi
d ar
thrit
is
repo
rt to
be
publ
ishe
d ea
rly 2
014.
iv) S
epsi
s m
odel
s re
port
to b
e pu
blis
hed
Spr
ing
2014
.v)
Insp
ecto
rs re
port
activ
e im
plem
enta
tion
by
licen
ce a
pplic
ants
.
i) M
easu
res
take
n to
elim
inat
e de
ath
as a
n en
dpoi
nt in
fish
di
seas
e st
udie
s to
redu
ce s
uffe
ring.
Thi
s re
pres
ents
bet
wee
n 76
% a
nd 9
4% o
f the
fish
wor
k of
the
Nat
iona
l Ref
eren
ce
Labo
rato
ry.
ii) R
efin
emen
t of t
he F
ish
Sex
ual D
evel
opm
ent T
est (
FSD
T)
for d
etec
ting
early
life
-sta
ge e
ffect
s an
d po
tent
ial a
dver
se
cons
eque
nces
of p
utat
ive
endo
crin
e di
srup
ting
com
poun
ds
on s
exua
l dev
elop
men
t (C
efas
- fu
ndin
g fro
m N
C3R
s). T
he
deve
lopm
ent o
f mol
ecul
ar m
arke
rs fo
r stic
kleb
ack
endo
crin
e fu
nctio
n an
d pr
otoc
ols
for s
tudy
ing
beha
viou
r of t
he a
nim
als
to
faci
litat
e a
decr
ease
in u
se o
f stic
kleb
acks
iii) N
C3R
s fu
ndin
g to
exa
min
e in
dica
tors
of f
ish
wel
lbei
ng.
i) A
ctiv
e ev
alua
tion
of d
iffer
ent w
ays
to re
duce
ani
mal
suf
ferin
g an
d an
imal
nu
mbe
rs u
sed.
The
new
pro
ject
lice
nce
for t
his
wor
k do
es n
ot in
clud
e de
ath
as a
n en
d-po
int.
ii) H
as re
sulte
d in
a 2
5% to
50%
redu
ctio
n in
the
num
ber o
f fis
h ne
eded
for t
his
test
. A
calc
ulat
ion
of th
e nu
mbe
r of c
hem
ical
s re
quiri
ng F
SD
T te
stin
g in
Eur
ope
alon
e sh
ows
that
use
of s
tickl
ebac
ks in
this
test
w
ill re
sult
in a
bout
90,
000
few
er fi
sh b
eing
sa
crifi
ced.
iii) P
roje
ct re
port
dem
onst
ratin
g be
tter f
ish
wel
fare
in e
xper
imen
tal s
yste
ms,
but
als
o m
ore
wid
ely
in fa
rmed
fish
in a
quac
ultu
re.
i) N
ew li
cenc
e al
read
y is
sued
; ref
inem
ent w
ork
ongo
ing.
ii) A
lread
y ac
hiev
ed
redu
ctio
n; fu
rther
im
prov
emen
t ong
oing
.
iii) O
ngoi
ng. R
epor
t in
2015
.
1.6
“Act
ual S
ever
ity”
Rep
ortin
g in
A
nnua
l Sta
tistic
s on
Use
of A
nim
als
in
Scie
nce
(HO
)
Impl
emen
t ret
rosp
ectiv
e re
porti
ng o
f the
“Act
ual S
ever
ity”
of a
ll sc
ient
ific
proc
edur
eson
pro
tect
ed a
nim
als
in li
ne w
ith
the
Dire
ctiv
e (2
010/
63/E
U).
This
will
ena
ble
us to
bet
ter
unde
rsta
nd:
- lev
els
of o
vera
ll an
imal
suf
ferin
g in
term
s of
num
bers
of
anim
als
expe
rienc
ing
each
cat
egor
y of
sev
erity
– s
ub-
thre
shol
d, m
ild, m
oder
ate
or s
ever
e;
- whi
ch p
roce
dure
s ar
e m
ost s
ever
e an
d in
whi
ch s
peci
es;
and
- whe
ther
3R
s im
plem
enta
tion
is h
avin
g an
impa
ct o
n re
duci
ng
over
all s
ever
ity.
i) C
ompl
etio
n an
d re
view
of p
ilot t
rial f
or
retro
spec
tive
(act
ual)
seve
rity
repo
rting
.ii)
Dev
elop
men
t of G
uida
nce
on re
cord
ing
Act
ual S
ever
ity.
iii) C
omm
ence
pro
ject
to m
ap p
heno
typi
ng
of G
A m
ouse
stra
ins
to a
ctua
l sev
erity
ca
tego
ries
com
men
ced
(with
ext
erna
l st
akeh
olde
rs e
.g. M
RC
Har
wel
l).iv
) Com
plet
ion
of a
naly
sis
of p
ilot d
ata
for
limite
d pu
blic
atio
n.v)
Pub
licat
ion
of fi
rst c
ompl
ete
year
of
retro
spec
tive
actu
al s
ever
ity d
ata.
vi
) Pro
visi
on o
f com
plet
e ye
ar d
ata
to th
e E
U C
omm
issi
on.
i) D
ecem
ber 2
013.
ii) J
anua
ry 2
014.
iii) M
arch
201
4.
iv) J
uly
2014
.
v) J
uly
2015
.
vi) B
y N
ovem
ber 2
015.
34
Da
elivering our Commitment to Replace, Reduce nd Refine the Use of Animals in Research
Title
/lead
org
anis
atio
n(s)
Act
ions
(und
erw
ay o
r pro
pose
d)M
easu
res
of s
ucce
ss a
nd k
ey
mile
ston
esTi
mel
ines
1.7
Cap
ture
of i
nfor
mat
ion
on s
cien
tific
ou
tput
s re
leva
nt to
3R
s an
d th
e im
plem
enta
tion
of 3
Rs
adva
nces
(MR
C a
nd B
BSR
C)
Res
earc
h C
ounc
ils to
impr
ove
the
capt
ure
of in
form
atio
n on
sc
ient
ific
outp
uts
rele
vant
to 3
Rs
and
the
impl
emen
tatio
n of
3R
s ad
vanc
es in
fund
ed p
roje
cts.
Dat
a on
3R
s im
plem
enta
tion
and
rele
vant
out
puts
cap
ture
d vi
a th
e in
trodu
ctio
n of
new
que
stio
ns in
the
Res
earc
h C
ounc
ils’
com
pute
rised
dat
a ga
ther
ing
syst
ems.
Enc
oura
gem
ent o
f oth
er c
harit
able
fund
ers
to d
o lik
ewis
e.
i) S
ucce
ssfu
l col
lect
ion
of c
aptu
red
data
.
ii) P
ublic
atio
n of
ana
lysi
s of
dat
a co
llect
ed.
iii) O
ther
maj
or c
harit
able
fund
ers
of a
nim
al
rese
arch
abl
e to
col
lect
com
para
ble
data
.
i) Fi
rst d
ata
colle
cted
aut
umn
2014
.ii)
Firs
t ana
lysi
s pu
blis
hed
sum
mer
20
15.
iii) O
ngoi
ng.
1.8
Upd
ated
requ
irem
ents
for
ap
plic
atio
ns w
hich
incl
ude
anim
al
rese
arch
(M
RC
and
BB
SRC
)
Res
earc
h C
ounc
ils to
issu
e up
date
d re
quire
men
ts a
nd g
uida
nce
for a
pplic
atio
ns w
hich
incl
ude
rese
arch
invo
lvin
g th
e us
e of
an
imal
s.E
nsur
e th
at e
very
rese
arch
pro
gram
me
and
proj
ect p
ropo
sal
rece
ives
effe
ctiv
e sc
rutin
y be
fore
it is
fund
ed a
nd th
at o
ppor
tuni
ties
to im
plem
ent s
cien
tific
adv
ance
s to
repl
ace,
redu
ce o
r ref
ine
anim
al
use
are
not m
isse
d.
i) D
rafti
ng a
nd is
suin
g of
new
gui
danc
e.
ii) E
valu
atio
n of
impa
ct o
f new
gui
danc
e.
i) N
ew g
uida
nce
in
plac
e by
Jan
201
4.ii)
Eva
luat
e th
e ef
fect
in th
e au
tum
n of
201
4.
1.9
Hig
hlig
ht o
n ‘A
nim
al W
elfa
re:
Mea
sure
s an
d as
sess
men
t’ (B
BSR
C a
nd N
C3R
s)
Dis
sem
inat
ion
even
t: B
BS
RC
join
t hig
hlig
ht w
ith N
C3R
s on
‘Ani
mal
W
elfa
re: M
easu
res
and
asse
ssm
ent’.
16 p
roje
cts
fund
ed to
talli
ng n
early
£5.
8M.
BB
SR
C w
orki
ng w
ith N
C3R
s to
ens
ure
that
ou
tput
s ar
e ca
ptur
ed a
nd d
isse
min
ated
to
ensu
re b
ette
r mon
itorin
g an
d as
sess
men
t of
wel
fare
in th
e fu
ture
.D
isse
min
atio
n ev
ents
dur
ing
the
cour
se o
f th
e pr
ogra
mm
e.
i) N
etw
orki
ng
wor
ksho
p fo
r gra
nt
hold
ers
Aut
umn
2013
.
ii) F
urth
er
diss
emin
atio
n ev
ents
pla
nned
w
ith o
ne a
gree
d fo
r S
prin
g 20
15.
1.10
Vet
erin
ary
vacc
ine
test
ing
(VM
D a
nd D
efra
)R
evie
w o
f bat
ch te
stin
g of
bio
logi
cals
suc
h as
vet
erin
ary
vacc
ines
.Id
entif
icat
ion
of a
reas
for p
ossi
ble
repl
acem
ent i
n th
e ba
tch
test
ing
of v
acci
nes,
esp
ecia
lly a
reas
of s
uch
test
ing
invo
lvin
g an
imal
s w
here
the
repl
acem
ent o
f the
test
wou
ld h
ave
the
bigg
est i
mpa
ct in
re
duci
ng n
umbe
r of a
nim
als
used
.
A re
port
setti
ng o
ut th
e nu
mbe
r of a
nim
als
used
dur
ing
in-p
roce
ss a
nd fi
nal p
rodu
ct
test
ing
of b
atch
es o
f vac
cine
s re
leas
ed b
y th
e V
MD
.
Rep
ort p
ublis
hed
2014
.
1.11
Hum
an V
acci
ne te
stin
g (P
HE)
.D
evel
opm
ent o
f 3R
s te
chni
ques
for u
se in
hum
an v
acci
ne
deve
lopm
ent.
i) W
orki
ng w
ith a
cade
mic
and
clin
ical
par
tner
s to
dev
elop
a B
CG
m
odel
that
allo
ws
asse
ssm
ent o
f effi
cacy
of n
ovel
TB
vac
cine
s w
hich
refin
e th
e us
e of
ani
mal
mod
els.
ii) A
ctiv
ely
deve
lopi
ng c
ell-b
ased
ass
ays
for t
he c
hara
cter
isat
ion
of
the
man
ufac
turin
g pr
oces
s an
d th
e ba
tch
rele
ase
of th
e pr
oduc
t, ev
alua
ting
the
pote
ntia
l to
repl
ace
toxi
city
rele
ase
test
s.
i) Th
is m
odel
has
the
pote
ntia
l to
refin
e th
e cu
rren
t tes
t to
allo
w fu
rther
dev
elop
men
t to
take
pla
ce a
t hum
an c
linic
al tr
ials
sta
ge.
ii) If
dev
elop
ed, t
he T
oxin
Neu
tralis
atio
n A
ssay
test
will
repl
ace
the
curr
ent p
oten
cy
test
res
ultin
g in
a re
duct
ion
in th
e nu
mbe
rs
of a
nim
als
used
and
the
seve
rity
of th
e te
stin
g.
i) O
ngoi
ng.
ii) O
ngoi
ng.
35
Delivering our Commitment to Replace, Reduce and Refine the Use of Animals in Research
Title
/lead
org
anis
atio
n(s)
Act
ions
(und
erw
ay o
r pro
pose
d)M
easu
res
of s
ucce
ss a
nd k
ey
mile
ston
esTi
mel
ines
1.12
Dev
elop
men
t of n
on-a
nim
al
tech
nolo
gies
(T
SB a
nd N
C3R
s)
Tech
nolo
gy S
trate
gy B
oard
(TS
B) d
evel
opm
ent o
f non
-ani
mal
te
chno
logi
es.
Com
petit
ion
to fu
nd e
arly
sta
ge fe
asib
ility
stu
dies
inve
stig
atin
g no
vel n
on-a
nim
al te
chno
logi
es to
impr
ove
prod
uct d
evel
opm
ent
acro
ss a
rang
e of
indu
strie
s. U
p to
£4
mill
ion
fund
ing
avai
labl
e.
Indu
stry
and
sec
tor i
nfom
ed o
f com
petit
ion
in a
utum
n 20
13 a
nd a
war
ds m
ade
in 2
014.
Out
put f
rom
the
fund
ed s
tudi
es w
ill b
e no
vel n
on-a
nim
al te
chno
logi
es th
at p
rodu
ce
appr
oach
es th
at a
re ‘f
it fo
r pur
pose
’.
i) C
ompe
titio
n op
ens
Febr
uary
20
14, c
lose
s A
pril
2014
.
ii) F
unde
d st
udie
s to
beg
in 2
014.
1.13
Ens
ure
gove
rnm
ent d
epar
tmen
ts
and
agen
cies
con
side
r the
3R
s w
hen
com
mis
sion
ing
or fu
ndin
g re
sear
ch
invo
lvin
g an
imal
s(G
CS
and
CSA
s)
Gov
ernm
ent C
hief
Sci
entis
t and
Dep
artm
enta
l Chi
ef S
cien
tific
A
dvis
ers
(CS
As)
to e
nsur
e th
at g
over
nmen
t dep
artm
ents
and
ag
enci
es c
onsi
der t
he 3
Rs
whe
n co
mm
issi
onin
g or
fund
ing
rese
arch
invo
lvin
g an
imal
s.C
omm
itmen
t fro
m d
epar
tmen
ts a
nd th
eir a
genc
ies
on th
e 3R
s in
clud
ing
polic
y st
atem
ents
ove
rsee
n by
the
CS
As.
i) A
ll go
vern
men
t dep
artm
ents
incl
udin
g
DH
, MoD
, Def
ra, H
O, B
IS a
nd a
genc
ies
have
sta
tem
ents
on
thei
r web
site
s.
i) O
ngoi
ng.
1.14
“M
inim
isat
ion
of a
nim
al te
stin
g”
leaf
let
(Def
ra a
nd H
SE)
As
UK
Com
pete
nt A
utho
rity
for R
EA
CH
, Def
ra a
nd H
SE
alre
ady
prod
uce
a le
afle
t ent
itled
“Min
imis
atio
n of
ani
mal
test
ing”
. Th
is
is a
pop
ular
pub
licat
ion
and
prov
ides
a b
rief s
umm
ary
of th
e op
portu
nitie
s th
at a
re a
vaila
ble
to R
EA
CH
regi
stra
nts
to m
inim
ise
the
amou
nt o
f ani
mal
test
ing
need
ed to
com
ply
with
RE
AC
H
regi
stra
tion.
Th
is in
itiat
ive
will
ens
ure
new
info
rmat
ion
abou
t adv
ance
s in
in v
itro
test
ing,
par
ticul
arly
of i
rrita
nts,
is c
omm
unic
ated
to U
K-b
ased
dut
y ho
lder
s.
i) U
pdat
e th
e pu
blic
atio
n “M
inim
isat
ion
of a
nim
al te
stin
g” w
hich
is p
opul
ar a
nd
effe
ctiv
e in
pro
mot
ing
the
3Rs
in th
is a
rea.
ii) E
ncou
rage
the
Eur
opea
n C
hem
ical
s A
genc
y (E
CH
A) t
o si
mila
rly u
pdat
e its
gu
idan
ce in
this
are
a fo
r tho
se w
ith
regi
stra
tion
dutie
s in
201
8.
i) P
ublis
h by
end
of
2014
.
ii) D
urin
g 20
14.
36
Da
elivering our Commitment to Replace, Reduce nd Refine the Use of Animals in Research
Title
/ lea
d or
gani
satio
n(s)
Act
ions
(und
erw
ay o
r pro
pose
d)M
easu
res
of s
ucce
ss a
nd k
ey m
ilest
ones
Tim
elin
es2.
1 N
C3R
s in
tern
atio
nal
scie
nce-
led
prog
ram
mes
2.1.
1 H
uman
tiss
ues
and
phar
mac
eutic
al d
evel
opm
ent
prog
ram
mes
(NC
3Rs
and
MH
RA
)
NC
3Rs/
MH
RA
join
t wor
king
gro
up o
n hu
man
tiss
ue fo
r sa
fety
pha
rmac
olog
y –
Join
t wor
king
gro
up to
gen
erat
e an
evi
denc
e ba
se to
sup
port
the
use
of h
uman
tiss
ue to
re
duce
ani
mal
s in
saf
ety
phar
mac
olog
y st
udie
s. T
he g
roup
co
nsis
ts o
f 25
phar
mac
eutic
al c
ompa
nies
, con
tract
rese
arch
or
gani
satio
ns, a
cade
mic
s an
d re
gula
tors
from
the
UK
, Eur
ope
and
US
A. T
his
form
s th
e ba
sis
of a
wid
er p
rogr
amm
e of
wor
k on
the
use
of h
uman
tiss
ue fo
r bas
ic a
nd a
pplie
d re
sear
ch,
incl
udin
g in
the
area
s of
ast
hma
and
pain
.
An
evid
ence
bas
e is
dev
elop
ed to
sup
port
the
use
of h
uman
tis
sue
to re
duce
the
use
of a
nim
als
in s
afet
y ph
arm
acol
ogy
stud
ies.
The
initi
al o
utpu
t of
the
wor
king
gr
oup
will
be
repo
rted
in s
prin
g 20
14.
NC
3Rs/
MH
RA
join
t wor
king
gro
up o
n re
cove
ry a
nim
als
in p
harm
aceu
tical
dev
elop
men
t – J
oint
wor
king
gro
up
to c
onsi
der p
oten
tial o
ppor
tuni
ties
for m
inim
isin
g th
e us
e of
reco
very
ani
mal
s (r
ats,
dog
s or
non
-hum
an p
rimat
es)
in p
harm
aceu
tical
dev
elop
men
t. Th
e gr
oup
cons
ists
of 3
2 ph
arm
aceu
tical
com
pani
es, c
ontra
ct re
sear
ch o
rgan
isat
ions
an
d re
gula
tors
from
the
UK
, Eur
ope
and
US
A, i
nclu
ding
the
FDA
.
Pot
entia
l opp
ortu
nitie
s ar
e id
entif
ied
to m
inim
ise
the
use
of
reco
very
ani
mal
s in
pha
rmac
eutic
al s
tudi
es.
The
initi
al o
utpu
t of
the
wor
king
gr
oup
will
be
repo
rted
in s
prin
g 20
14.
2.1.
2 C
hem
ical
saf
ety
prog
ram
me
(NC
3Rs,
HSE
and
PH
E)
NC
3Rs
wor
king
gro
up o
n th
e fix
ed c
once
ntra
tion
proc
edur
e (c
hem
ical
saf
ety)
– T
his
wor
king
gro
up s
uppo
rts
the
inte
rnat
iona
l ado
ptio
n of
the
fixed
con
cent
ratio
n pr
oced
ure
(FC
P) f
or a
cute
inha
latio
n to
xici
ty te
stin
g. T
he N
C3R
s is
w
orki
ng w
ith in
hala
tion
toxi
city
exp
erts
from
con
tract
rese
arch
or
gani
satio
ns, a
cade
mia
, and
oth
er g
over
nmen
t bod
ies,
to
mak
e th
e FC
P m
ore
obje
ctiv
e to
enc
oura
ge w
ider
ado
ptio
n of
th
e ap
proa
ch a
cros
s O
EC
D M
embe
r Sta
tes.
Obj
ectiv
e sc
orin
g sy
stem
to e
ncou
rage
wid
er a
dopt
ion
of F
CP
ac
ross
OE
CD
mem
ber s
tate
s.Th
e ou
tput
of
this
wor
k w
ill
be p
ublis
hed
in
sprin
g 20
14.
Stra
tegi
c Pr
iorit
y 2
– In
fluen
cing
the
upta
ke a
nd a
dopt
ion
of 3
Rs
appr
oach
es g
loba
lly
37
Delivering our Commitment to Replace, Reduce and Refine the Use of Animals in Research
Title
/ lea
d or
gani
satio
n(s)
Act
ions
(und
erw
ay o
r pro
pose
d)M
easu
res
of s
ucce
ss a
nd k
ey m
ilest
ones
Tim
elin
es2.
2 R
evie
w o
f OEC
D T
est
Gui
delin
es
2.2.
1 Sy
stem
atic
revi
ew o
f O
ECD
Tes
t Gui
delin
es to
ad
dres
s 3R
s
(Def
ra a
nd P
HE)
2.2.
2 R
epro
duct
ive
toxi
colo
gy (E
OG
RTS
)
(Def
ra a
nd H
SE)
Sys
tem
atic
revi
ew o
f Org
anis
atio
n fo
r Eco
nom
ic C
o-op
erat
ion
and
Dev
elop
men
t (O
EC
D) T
est G
uide
lines
(TG
s) to
add
ress
3R
s.
In li
aiso
n w
ith in
dust
ry p
artn
ers
as w
ell a
s re
gula
tory
au
thor
ities
, we
will
revi
ew T
Gs
whe
re a
pot
entia
l to
repl
ace,
re
duce
or r
efin
e an
imal
stu
dies
is id
entif
ied.
Cur
rent
wor
k is
on
skin
and
eye
sen
sitis
atio
n an
d irr
itatio
n (s
ee a
lso
Act
ion
1.14
). P
ropo
sed
addi
tiona
l wor
k is
on
the
acut
e de
rmal
toxi
city
. All
are
area
s w
here
the
a re
view
of t
he p
roto
cols
wou
ld n
ot o
nly
addr
ess
3Rs
but p
rovi
de a
n ad
vanc
e in
sci
ence
.
i) A
dopt
ion
of T
G u
nder
revi
ew T
G43
0 an
d TG
431
S
kin
irrita
tion
and
corr
osio
n.
ii) S
ubm
it pr
opos
al to
OE
CD
for r
evie
w o
f the
use
of b
oth
gend
ers
in th
e ac
ute
derm
al to
xici
ty a
ssay
(TG
402)
.
iii) C
omm
ence
revi
ew o
f dat
a fo
r the
use
of b
oth
gend
ers
in
the
acut
e de
rmal
toxi
city
ass
ay (T
G40
2).
i) A
pril
2014
.
ii) J
anua
ry 2
014.
iii) J
une
2014
.
The
Ext
ende
d O
ne-G
ener
atio
n R
epro
duct
ive
Toxi
city
Stu
dy
(EO
GR
TS) o
ffers
a m
uch
mor
e fle
xibl
e st
udy
desi
gn th
an
the
tradi
tiona
l tw
o-ge
nera
tion
appr
oach
(OE
CD
TG
416)
. The
E
OG
RTS
has
bee
n sh
own
to g
ener
ate
suffi
cien
t inf
orm
atio
n fo
r reg
ulat
ory
purp
oses
with
out t
he m
anda
tory
pro
duct
ion
of a
se
cond
gen
erat
ion.
The
EO
GR
TS u
ses
abou
t hal
f the
num
ber
of a
nim
als
– re
duci
ng fr
om 2
,600
to 1
,400
rats
per
test
. It w
as
adop
ted
by th
e O
EC
D in
to it
s te
st g
uide
lines
in 2
009.
i) In
ass
ocia
tion
with
com
pete
nt a
utho
ritie
s fro
m o
ther
key
EU
M
embe
r Sta
tes,
to p
rom
ote
the
adop
tion
of th
e E
OG
RTS
in
the
EU
.
ii) T
o co
mpl
ete
the
proc
ess
by a
chie
ving
ado
ptio
n of
the
EO
GR
TS in
the
RE
AC
H T
est M
etho
ds R
egul
atio
n.
i) O
ngoi
ng.
ii) S
umm
er 2
014.
2.3
Influ
ence
regu
lato
ry
fram
ewor
ks w
hich
requ
ire
anim
al te
stin
g:
2.3.
1. A
dver
se O
utco
me
Path
way
s fo
r che
mic
als
(PH
E an
d D
efra
)
Adv
erse
Out
com
e Pa
thw
ays
– In
tern
atio
nal D
evel
opm
ent o
f N
ew A
ppro
ache
s to
Che
mic
als
Test
ing.
His
toric
ally,
iden
tifyi
ng a
dver
se e
ffect
s of
che
mic
als
has
relie
d on
usi
ng la
rge
num
bers
of a
nim
als
to te
st th
eir t
oxic
ity, o
ne
by o
ne. I
f we
coul
d id
entif
y th
e ch
ain
of li
nked
eve
nts
from
an
initi
al c
hem
ical
impa
ct a
t the
mol
ecul
ar le
vel t
o re
spon
ses
at h
ighe
r bio
logi
cal l
evel
s, w
e m
ight
be
able
to u
se in
vitr
o te
chni
ques
suc
h as
gen
omic
s to
pre
dict
impa
cts
up to
the
leve
l of
an
orga
nism
or e
ven
popu
latio
ns. T
his
wou
ld o
ffer w
ays
of
redu
cing
the
need
for t
ests
usi
ng in
tact
ani
mal
s, a
s w
ell a
s sp
eedi
ng u
p th
e as
sess
men
t of c
hem
ical
s. T
he c
once
pt o
f A
dver
se O
utco
me
Pat
hway
s (A
OP
s) o
ffers
a m
echa
nist
ic w
ay
to d
escr
ibe
such
a s
eque
ntia
l cha
in o
f cau
sally
link
ed e
vent
s.
In 2
012,
the
OE
CD
laun
ched
a n
ew p
rogr
amm
e to
dev
elop
A
OP
s, in
whi
ch th
e U
K is
col
labo
ratin
g.
App
ropr
iate
AO
Ps
to b
e va
lidat
ed a
nd in
corp
orat
ed in
to O
EC
D
Test
Met
hods
tool
kit a
s qu
ickl
y as
pos
sibl
e, v
ia o
utpu
ts o
f UK
-fu
nded
rese
arch
mad
e av
aila
ble
to th
e O
EC
D p
rogr
amm
e.
Thre
e re
leva
nt p
roje
cts
are
unde
rway
:
i) U
K-J
apan
col
labo
rativ
e pr
ojec
t – C
ritic
al re
view
of k
ey
know
ledg
e ga
ps to
sup
port
AO
Ps
for O
EC
D te
st g
uide
lines
for
aqua
tic o
rgan
ism
s. D
eliv
ery
of c
ritic
al re
view
of k
ey k
now
ledg
e ga
ps to
sup
port
AO
Ps
for O
EC
D te
st g
uide
lines
for a
quat
ic
orga
nism
s de
liver
ed b
y U
K a
nd J
apan
.
ii) D
efra
-fund
ed p
roje
ct (C
ranf
ield
Uni
vers
ity) –
In S
ilico
P
redi
ctio
ns o
f In
vivo
Tox
icity
: Are
inte
rspe
cies
ext
rapo
latio
ns
off t
ange
nt.
Fina
l rep
ort p
ublis
hed
on a
ccur
acy
of in
ter-
spec
ies
extra
pola
tions
of i
n si
lico
pred
ictio
ns o
f in
vivo
toxi
city
.
iii) D
efra
-fund
ed p
roje
ct (C
efas
, Uni
vers
ities
of B
irmin
gham
an
d Li
verp
ool)
- The
use
of s
yste
ms
toxi
colo
gy to
re-c
onst
ruct
m
olec
ular
AO
Ps
– ca
n ch
emic
al m
ixtu
re to
xici
ty b
e pr
edic
ted
to a
id e
nviro
nmen
tal r
isk
asse
ssm
ent a
nd re
gula
tion?
Fin
al
repo
rt pu
blis
hed
on th
e us
e of
sys
tem
s to
xico
logy
to re
-co
nstru
ct m
olec
ular
AO
Ps.
i) Ju
ne 2
014.
ii) S
epte
mbe
r 20
14.
iii) M
arch
201
5.
38
Da
elivering our Commitment to Replace, Reduce nd Refine the Use of Animals in Research
Title
/ lea
d or
gani
satio
n(s)
Act
ions
(und
erw
ay o
r pro
pose
d)M
easu
res
of s
ucce
ss a
nd k
ey m
ilest
ones
Tim
elin
es2.
3.2
App
roac
hes
for
phar
mac
eutic
als
(MH
RA
and
VMD
)
Har
mon
isat
ion
of a
ppro
ache
s w
ithin
regu
lato
ry
fram
ewor
ks:
- Har
mon
ise
appr
oach
es w
ith re
spec
t to
the
3Rs,
and
pro
mot
e th
eir u
ptak
e in
pha
rmac
eutic
al d
evel
opm
ent.
- Con
tribu
te to
ong
oing
exp
lora
tion
of a
ltern
ativ
es to
usi
ng
anim
als
in te
stin
g of
haz
ardo
us m
ater
ials
.
Sup
port
the
harm
onis
atio
n of
glo
bal r
egul
ator
y st
anda
rds.
U
nles
s al
l reg
ulat
ors
acce
pt a
n al
tern
ativ
e to
an
anim
al te
st,
the
anim
al te
st w
ould
stil
l be
carr
ied
out b
y in
dust
ry to
ens
ure
wid
espr
ead
mar
ketin
g –
esse
ntia
lly p
erfo
rmin
g to
the
‘low
est
com
mon
dom
inat
or’ (
and
high
est a
nim
al u
se) d
espi
te b
ette
r an
d m
ore
econ
omic
test
s be
ing
avai
labl
e.
Con
tinue
to w
ork
with
oth
er re
gula
tory
age
ncie
s to
inte
rpre
t IC
H a
nd V
ICH
flex
ibly,
esp
ecia
lly in
ligh
t of e
mer
ging
mar
kets
w
hich
are
kno
wn
to b
e le
ss fl
exib
le.
Con
tinue
to in
sist
of a
dher
ence
of O
EC
D G
ood
Labo
rato
ry
Pra
ctic
e (G
LP) r
equi
rem
ents
to a
void
dup
licat
ion
of s
tudi
es,
espe
cial
ly im
porta
nt fo
r em
ergi
ng m
arke
ts w
hich
are
not
par
ty
to th
e M
utua
l Acc
epta
nce
of D
ata
proc
edur
es.
Pro
vide
a c
halle
nge
to in
dust
ry fo
r alre
ady
auth
oris
ed p
roje
cts
and
high
light
whe
re th
ey a
re p
erfo
rmin
g un
nece
ssar
y an
imal
te
stin
g an
d se
t out
our
exp
ecta
tions
for c
hang
e.
i) M
HR
A en
gage
d at
Eur
opea
n an
d w
ider
inte
rnat
iona
l le
vels
with
pha
rmac
eutic
al re
gula
tors
to p
rom
ote
the
upta
ke
of th
e 3R
s an
d ha
rmon
ise
appr
oach
es a
t all
stag
es o
f ph
arm
aceu
tical
dev
elop
men
t.ii)
MH
RA
enco
urag
ing
the
use
of m
ultip
le e
nd-p
oint
s in
one
st
udy
to w
ork
to re
duce
the
use
of a
nim
als
– an
exa
mpl
e w
ould
be
incl
udin
g ge
noto
xici
ty te
stin
g in
ani
mal
s in
oth
er
toxi
city
stu
dies
. iii
) VM
D a
nd M
HR
A in
fluen
cing
the
deve
lopm
ent a
nd re
visi
on
of E
urop
ean
Pha
rmac
opoe
ia m
onog
raph
s su
ch th
at, w
here
ver
feas
ible
, tes
ting
in a
nim
als
is re
plac
ed o
r rem
oved
or r
efin
ed.
(Thi
s cr
eate
s a
wid
er o
utre
ach
than
sim
ply
the
EU
as
mor
e co
untri
es a
re s
igne
d up
to th
e ph
arm
acop
eia.
)iv
) VM
D p
artic
ipat
ing
in th
e C
XM
P 3R
s gr
oup
whi
ch is
in
tend
ed to
iden
tify
and
prog
ress
are
as fo
r reg
ulat
ory
chan
ge
whi
ch c
an e
nabl
e re
duce
d te
stin
g in
ani
mal
s.v)
VM
D a
nd M
HR
A ac
tivel
y ch
alle
ngin
g in
dust
ry fo
r alre
ady
auth
oris
ed p
roje
cts
and
high
light
ing
whe
re th
ey m
ay b
e pe
rform
ing
unne
cess
ary
anim
al te
stin
g. S
ettin
g ou
t our
ex
pect
atio
ns fo
r cha
nge.
vi
) Def
ra p
roje
ct to
revi
ew o
f acc
urac
y of
inte
r-sp
ecie
s ex
trapo
latio
ns o
f in
silic
o pr
edic
tions
of i
n vi
vo to
xici
ty.
i) O
ngoi
ng.
ii) O
ngoi
ng.
iii) O
ngoi
ng.
iv) O
ngoi
ng.
v) O
ngoi
ng.
vi) S
epte
mbe
r 20
14 –
fina
l rep
ort
publ
ishe
d.
39
Delivering our Commitment to Replace, Reduce and Refine the Use of Animals in Research
Title
/ lea
d or
gani
satio
n(s)
Act
ions
(und
erw
ay o
r pro
pose
d)M
easu
res
of s
ucce
ss a
nd k
ey m
ilest
ones
Tim
elin
es2.
3.3.
Pro
mot
e 3R
s in
food
sa
fety
regu
latio
n
(FSA
and
Cef
as fo
r Mou
se
bioa
ssay
repl
acem
ent)
(FSA
for o
ther
opp
ortu
nitie
s)
3. U
ptak
e of
3R
s an
d re
sear
ch /
risk
asse
ssm
ent t
o pr
omot
e al
tern
ativ
es.
- Pro
mot
e up
take
of 3
Rs
in fo
od s
afet
y re
gula
tion
and
supp
ort
test
ing
requ
irem
ents
in th
e U
K a
nd E
U.
- Pro
mot
e an
d su
ppor
t res
earc
h an
d ris
k as
sess
men
t to
unde
rpin
ado
ptio
n of
alte
rnat
ives
to a
nim
al-b
ased
test
ing
for f
ood
safe
ty w
here
this
can
be
done
whi
le m
aint
aini
ng a
n ad
equa
te le
vel o
f con
sum
er p
rote
ctio
n.
Key
opp
ortu
nitie
s ex
ist i
n re
latio
n to
:
- To
repl
ace
mou
se b
ioas
say
in te
stin
g fo
r she
llfis
h bi
otox
ins
(i
and
ii).
- To
cont
inue
to e
ncou
rage
the
Eur
opea
n C
omm
issi
on a
nd
othe
r Mem
ber S
tate
s to
con
side
r the
3R
s pr
inci
ple
whe
n de
term
inin
g th
e ne
ed fo
r ani
mal
stu
dies
in th
e ris
k as
sess
men
t of
GM
Os
(iii).
- Eng
agem
ent w
orld
wid
e w
ith fo
od ri
sk a
sses
smen
t and
re
gula
tory
bod
ies
to d
evel
op a
nd h
arm
onis
e ap
proa
ches
an
d to
refle
ct th
ese
and
the
3Rs
in n
ew o
r upd
ated
food
re
gula
tions
and
test
ing
requ
irem
ents
. Unl
ess
all r
egul
ator
s ac
cept
an
alte
rnat
ive
to a
n an
imal
test
, the
ani
mal
test
may
st
ill b
e ca
rrie
d ou
t by
indu
stry
to e
nsur
e w
ides
prea
d ac
cess
to
mar
kets
des
pite
bet
ter a
nd m
ore
econ
omic
test
s be
ing
avai
labl
e (iv
).- C
onsi
derin
g th
e m
ost a
ppro
pria
te m
eans
of g
ener
atin
g da
ta
on a
ppro
ved
food
che
mic
als,
incl
udin
g hu
man
stu
dies
whe
re
thes
e ar
e et
hica
l and
app
ropr
iate
(v).
- Cle
ar g
uida
nce
on th
e re
quire
men
ts fo
r aut
horis
atio
n of
nov
el
food
s an
d pr
oces
ses
(vi).
i) S
ucce
ssfu
l rep
lace
men
t of m
ouse
bio
assa
y in
con
trols
on
shel
lfish
toxi
ns in
UK
. ii)
See
k co
mm
itmen
t fro
m C
omm
issi
on to
ens
ure
othe
r EU
M
embe
r Sta
tes
repl
ace
mou
se b
ioas
say.
iii) K
ey o
ppor
tuni
ties
to in
fluen
ce in
clud
e w
hen
the
EU
FP
7 “G
RA
CE
” pro
ject
com
es to
frui
tion,
and
whe
n th
e C
omm
issi
on’s
two-
year
feed
ing
stud
y w
ith G
M m
aize
is
com
plet
ed.
iv) F
SA
and
its in
depe
nden
t sci
entif
ic a
dvis
ory
com
mitt
ees
are
enga
ged
at E
U a
nd w
ider
inte
rnat
iona
l lev
els,
incl
udin
g st
rong
en
gage
men
t with
the
EFS
A, t
he C
omm
issi
on, J
EC
FA a
nd
Cod
ex A
limen
tariu
s.
v) A
n ex
ampl
e is
com
mis
sion
ing
epid
emio
logi
cal s
tudi
es
to p
rovi
de a
bas
is fo
r adv
ice
on c
affe
ine
inta
kes
durin
g pr
egna
ncy.
vi) F
SA
prov
ide
clea
r gui
danc
e to
indu
stry
on
the
requ
irem
ents
fo
r app
licat
ions
for a
utho
risat
ion
of n
ovel
food
s an
d pr
oces
ses
on w
here
ani
mal
test
ing
is a
nd is
not
nec
essa
ry fo
r app
rova
l.
i) C
ompl
eted
.
ii) D
urin
g 20
14.
iii) D
urin
g E
U F
P7
‘GR
AC
E’ p
roje
ct
and
two-
year
fe
edin
g st
udy
with
G
M m
aize
.iv
) Ong
oing
.
v) O
ngoi
ng.
vi) O
ngoi
ng.
40
Da
elivering our Commitment to Replace, Reduce nd Refine the Use of Animals in Research
Title
/ lea
d or
gani
satio
n(s)
Act
ions
(und
erw
ay o
r pro
pose
d)M
easu
res
of s
ucce
ss a
nd k
ey m
ilest
ones
Tim
elin
es2.
4 C
osm
etic
s al
tern
ativ
es
(BIS
and
indu
stry
with
su
ppor
t fro
m H
O a
nd F
CO
–
see
also
2.5
bel
ow)
- Wor
k pl
an b
eing
dev
elop
ed to
influ
ence
oth
er n
on-E
U
coun
tries
in u
sing
alte
rnat
ives
to a
nim
al te
stin
g in
brin
ging
co
smet
ics
to m
arke
t (se
e al
so 2
.5 b
elow
).- A
cces
s to
dat
a se
t on
wha
t thi
rd c
ount
ries
requ
ire a
s an
imal
te
stin
g an
d w
hat t
hey
requ
ire to
be
test
ed.
- Con
side
r opt
ions
of h
ow th
e E
U s
yste
m (r
elia
nce
on
ingr
edie
nt s
afet
y) c
ould
be
adap
ted
for t
hird
cou
ntrie
s su
ch a
s C
hina
to fa
cilit
ate
trade
.
i) P
aper
dev
elop
ed.
ii) O
utlin
e of
geo
grap
hies
and
type
s of
test
whe
re w
e th
ink
ther
e is
redu
ndan
t ani
mal
test
ing
to ta
rget
focu
s.iii
) Opt
ions
for r
evis
ing
(pos
sibl
y ba
sed
on th
e E
U m
odel
) in
clud
ing
oppo
rtuni
ties
for r
efor
m id
entif
ied
(e.g
. in
Chi
na).
i) F
ebru
ary
2014
.ii)
Dur
ing
2014
.
iii) 2
014
and
ongo
ing.
2.5
Dev
elop
ing
Act
ion
Plan
pr
iorit
ies
into
an
effe
ctiv
e in
tern
atio
nal c
omm
unic
atio
n an
d in
fluen
cing
str
ateg
y
(FC
O, H
O a
nd B
IS-S
IN)
Usi
ng B
IS-S
IN G
loba
l Par
tner
ship
Fun
d, to
sup
port
a U
K
colla
bora
tion
with
Chi
na fo
r a tw
o-da
y se
min
ar, f
unde
d jo
intly
by
UK
Gov
ernm
ent a
nd th
e re
leva
nt p
harm
aceu
tical
an
d co
smet
ics
indu
strie
s, fo
r inv
ited
expe
rts (g
over
nmen
t, ac
adem
ia a
nd in
dust
ry) f
rom
Chi
na a
nd o
vers
eas
(UK
/EU
/US
) to
be
held
in B
eijin
g.
i) O
rgan
ise
sem
inar
in B
eijin
g to
sup
port
deve
lopm
ent o
f st
anda
rds
for a
nim
al c
are,
wel
fare
and
eth
ical
use
in re
sear
ch.
ii) W
ork
tow
ards
end
orse
men
t of s
tand
ards
by
Chi
nese
au
thor
ities
. iii
) Ini
tiate
a d
ialo
gue
on h
arm
onis
ing
phar
mac
eutic
al s
afet
y te
stin
g gu
idel
ines
and
dev
elop
a fo
rwar
d pl
an.
iv) E
xplo
re a
stra
tegy
to c
ease
ani
mal
test
ing
of c
osm
etic
s in
C
hina
whe
reve
r it i
s no
t sci
entif
ical
ly n
eces
sary
.
i) M
arch
201
4.
ii) S
umm
er 2
014.
iii) M
arch
201
4 an
d on
goin
g.iv
) Mar
ch 2
014
and
ongo
ing.
Inte
rnat
iona
l lob
byin
g, in
fluen
cing
and
evi
denc
e ga
ther
ing
com
mun
icat
ions
man
aged
by
FCO
Sci
ence
and
Inno
vatio
n N
etw
ork,
in p
artn
ersh
ip w
ith B
IS a
nd H
ome
Offi
ce le
ads,
th
roug
h th
e FC
O g
loba
l stru
ctur
e.
Inte
rnat
iona
l Act
ion
Pla
n pr
iorit
ies
deliv
ered
: Del
iver
y P
lan
partn
ers
with
an
inte
rnat
iona
l com
pone
nt to
thei
r act
ivity
abl
e to
acc
ess
FCO
net
wor
k ef
ficie
ntly
/effe
ctiv
ely
with
tim
ely
inpu
t of
inte
rnat
iona
l fee
dbac
k an
d ev
iden
ce a
s re
quire
d.
Ong
oing
.
41
Delivering our Commitment to Replace, Reduce and Refine the Use of Animals in Research
Stra
tegi
c Pr
iorit
y 3
– Pr
omot
ing
an u
nder
stan
ding
and
aw
aren
ess
abou
t the
use
of a
nim
als
whe
re n
o al
tern
ativ
es e
xist
Ti
tle/le
ad
orga
nisa
tion(
s)A
ctio
ns (u
nder
way
or p
ropo
sed)
Mea
sure
s of
suc
cess
and
key
mile
ston
esTi
mel
ines
3.1
Impr
ovin
g pu
blic
un
ders
tand
ing
of
anim
al re
sear
ch
(BIS
)
Impr
ovin
g pu
blic
und
erst
andi
ng o
f the
con
text
of a
nim
al re
sear
ch a
nd th
e lic
ensi
ng fr
amew
ork.
- R
evie
w th
e re
spon
ses
to a
nim
al re
sear
ch q
uest
ions
con
tain
ed w
ithin
th
e P
ublic
Atti
tude
s S
urve
y 20
14 m
anag
ed b
y S
cien
ce a
nd S
ocie
ty a
nd
forth
com
ing
attit
udin
al s
urve
y.- O
ffice
of L
ife S
cien
ces
(OLS
) lea
ding
Pol
l on
anim
al re
sear
ch.
Pre
viou
s po
lls (B
IS) s
how
an
enha
nced
pub
lic
unde
rsta
ndin
g of
the
regu
lato
ry fr
amew
ork
with
in
whi
ch a
nim
als
are
used
in th
e U
K.
i) 20
14 p
oll l
aunc
hed
ii) E
vide
nce
of e
nhan
ced
publ
ic u
nder
stan
ding
thro
ugh
new
pol
l res
ults
.
i) M
arch
201
4.ii)
Lat
e 20
14.
3.2
Incr
ease
d tr
ansp
aren
cy a
bout
ac
tual
sev
erity
(HO
)
Dis
aggr
egat
ion
of d
ata
to re
port
proc
edur
es a
ccor
ding
to th
eir a
ctua
l sev
erity
.M
ore
clea
rly s
epar
ate
the
num
ber o
f pro
cedu
res
asso
ciat
ed w
ith th
e br
eedi
ng
of n
on-h
arm
ful G
M a
nim
als
(invo
lvin
g no
suf
ferin
g) fr
om p
ainf
ul p
roce
dure
s in
an
imal
s.[L
ink
to A
ctio
n 1.
6] B
ette
r inf
orm
the
publ
ic a
bout
wha
t ani
mal
rese
arch
co
mpr
ises
(lar
gely
mild
or s
ub-th
resh
old)
as
wel
l as
to id
entif
y th
e m
ost s
ever
e pr
oced
ures
and
dev
elop
way
s to
redu
ce th
at s
ever
ity.
i) C
ompl
etio
n an
d re
view
of p
ilot t
rial f
or re
trosp
ectiv
e (a
ctua
l) se
verit
y re
porti
ng.
ii) D
evel
opm
ent o
f Gui
danc
e on
reco
rdin
g A
ctua
l S
ever
ity.
iii) C
omm
ence
pro
ject
to m
ap p
heno
typi
ng o
f G
A m
ouse
stra
ins
to a
ctua
l sev
erity
cat
egor
ies
com
men
ced
(with
ext
erna
l sta
keho
lder
s e.
.g. M
RC
H
arw
ell).
iv) C
ompl
etio
n of
ana
lysi
s of
pilo
t dat
a fo
r lim
ited
publ
icat
ion.
v) P
ublic
atio
n of
firs
t com
plet
e ye
ar o
f ret
rosp
ectiv
e ac
tual
sev
erity
dat
a.
vi) P
rovi
sion
of c
ompl
ete
year
dat
a to
the
EU
C
omm
issi
on.
i) D
ecem
ber 2
013.
ii) J
anua
ry 2
014.
iii) M
arch
201
4.
iv) J
uly
2014
.
v) J
uly
2015
.
vi) B
y N
ovem
ber
2015
.
3.3
Con
cord
at o
n O
penn
ess
and
Tran
spar
ency
(Aca
dem
ia, i
ndus
try,
he
alth
cha
ritie
s,
fund
ers,
etc
.)
Con
cord
at o
n O
penn
ess
and
Tran
spar
ency
to b
e m
ore
open
abo
ut th
e w
ays
in w
hich
ani
mal
s ar
e us
ed in
sci
entif
ic, m
edic
al a
nd v
eter
inar
y re
sear
ch in
the
UK
.- C
onco
rdat
on
Ope
nnes
s ab
out a
nim
al re
sear
ch a
gree
d be
twee
n m
ajor
fu
nder
s, re
sear
ch o
rgan
isat
ions
and
indu
stry
. - I
PS
OS
MO
RI r
epor
t on
Sci
ence
wis
e su
ppor
ted
publ
ic d
ialo
gue
sess
ions
will
de
term
ine
publ
ic e
xpec
tatio
ns o
f ope
nnes
s, tr
ansp
aren
cy a
nd c
omm
unic
atio
n to
info
rm th
e de
velo
pmen
t of t
he C
onco
rdat
on
the
use
of a
nim
als
in re
sear
ch.
i) P
ublic
atio
n of
dec
lara
tion
on o
penn
ess.
ii) P
ublic
atio
n of
Con
cord
at.
iii) A
nnua
l mon
itorin
g sh
ows
prog
ress
in
impl
emen
tatio
n.
iv) P
olls
sho
w in
crea
sed
publ
ic u
nder
stan
ding
of t
he
role
of a
nim
al re
sear
ch.
i) D
ecla
ratio
n on
ope
nnes
s pu
blis
hed
Oct
ober
20
12.
ii) P
ublic
atio
n of
C
onco
rdat
Spr
ing
2014
.iii
) Ong
oing
.iv
) Nex
t pol
l 201
4.
3.4
Rev
iew
of s
ectio
n 24
of A
SPA
(HO
)
The
Gov
ernm
ent t
o re
view
sec
tion
24 o
f the
Ani
mal
s (S
cien
tific
Pro
cedu
res)
A
ct 1
986
(AS
PA).
Sec
tion
24 p
rovi
des
for t
he p
rote
ctio
n of
info
rmat
ion,
giv
en in
con
fiden
ce,
in c
onne
ctio
n w
ith re
gula
tory
act
iviti
es u
nder
AS
PA. A
bre
ach
of s
ectio
n 24
ca
n re
sult
in c
rimin
al s
anct
ions
. The
infle
xibl
e co
nfid
entia
lity
requ
irem
ents
of
sec
tion
24 a
re n
ow o
ut o
f ste
p w
ith g
over
nmen
t pol
icy
on o
penn
ess
and
trans
pare
ncy
and
with
the
appr
oach
take
n in
oth
er le
gisl
atio
n, s
uch
as th
e Fr
eedo
m o
f Inf
orm
atio
n A
ct (F
OIA
). Th
e in
tent
ion
is to
des
ign
a m
ore
flexi
ble
fram
ewor
k th
at w
ill p
rote
ct p
ropr
ieta
ry ri
ghts
, int
elle
ctua
l pro
perty
and
per
sona
l sa
fety
, pro
vide
gre
ater
tran
spar
ency
to a
ssis
t pub
lic u
nder
stan
ding
, and
not
ha
rm th
e co
mpe
titiv
enes
s of
the
UK
in th
e Li
fe S
cien
ces.
i) P
ublic
con
sulta
tion
on o
ptio
ns fo
r rev
isio
n of
sec
tion
24 c
omm
ence
d.
ii) R
espo
nse
to p
ublic
con
sulta
tion
revi
ewed
and
pr
efer
red
optio
n pr
epar
ed.
iii) P
roce
sses
for l
egis
lativ
e ch
ange
s (a
s ne
eded
) pu
rsue
d le
adin
g to
revi
sion
of s
ectio
n 24
.
i) B
y Ja
nuar
y 20
14.
ii) B
y M
ay 2
014.
iii) T
imin
g de
pend
s on
legi
slat
ive
vehi
cle
need
ed.
42
Delivering our Commitment to Replace, Reduce and Refine the Use of Animals in Research
Glossary
3Rs The principles of replacement, reduction and refinement – an ethical framework for conducting scientific experiments using animals humanely
AHVLA Animal Health & Veterinary Laboratories Agency, an executive agency of Defra
ASPA Animals (Scientific Procedures) Act 1986 (as amended in 2012)
ASRU Animals in Science Regulation Unit, a unit of the Home Office responsible for regulating the use of animals in research under ASPA
AWERB Animal Welfare and Ethical Review Body, a requirement of each research establishment licensed under ASPA
BBSRC Biotechnology & Biological Sciences Research Council, an executive NDPB of BIS investing in bioscience research and training in the UK
BIS Department for Business, Innovation and Skills
Cefas Centre for Environment, Fisheries & Aquaculture Science, an executive agency of Defra
CFDA The Food and Drug Administration responsible for registration, including pharmaceuticals, medical devices and cosmetics, in China
Defra Department for Environment, Food and Rural Affairs
DH Department of HealthECHA European Chemicals Agency responsible for
the REACH RegulationEOGRTS Extended One-Generation Reproductive
Toxicity Study FCO Foreign & Commonwealth Office Fera Food & Environment Research Agency, an
executive agency of DefraFRAME Fund for the Replacement of Animals in
Medical ExperimentsFSA Food Standards Agency, a non-ministerial
department responsible for food safety and food hygiene across the UK
GA Genetically altered (applied to animals)GO-Science The Government Office for Science
which works within BIS and supports the Government Chief Scientific Adviser
HSE Health & Safety Executive, an executive NDPB of the Department for Work & Pensions and the UK competent authority for REACH
ICH International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use
in vitro research using methods in components of an organism (e.g. tissue culture, cells, subcellular extracts or purified molecules)
in vivo research using methods within a whole, living organism, usually an animal
MHRA Medicines and Healthcare Products Regulatory Agency, an executive agency of DH responsible for registration of human medicines, vaccines and other healthcare products in the UK
MRC Medical Research Council, an executive NDPB of BIS which aims to improve human health by supporting research in medical sciences
NC3Rs The National Centre for the Replacement, Refinement & Reduction of Animals in Research
NDPB Non-departmental public bodyOECD Organisation for Economic Co-operation and
DevelopmentPHE Public Health England, an executive agency
of DH which aims to protect and improve human health in the UK
REACH Registration, Evaluation, Authorisation & restriction of Chemicals, an EU regulation which addresses the potential impact of chemicals on human health and the environment
RSPCA Royal Society for the Prevention of Cruelty to Animals, a UK scientific animal welfare charity
TSB Technology Strategy Board, an executive NDPB sponsored and funded by BIS
UFAW Universities Federation for Animal Welfare – an internationally recognised, independent, scientific and educational animal welfare charity which first promoted the concept of the 3Rs
US FDA US Food and Drug Administration, an operating division of the US Department of Health & Human Services responsible for ensuring that human and animal pharmaceuticals, medical devices and cosmetics in the USA are safe and effective
VICH The International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products
VMD Veterinary Medicines Directorate, an executive agency of Defra responsible for registration of veterinary medicines, vaccines and other animal health products in the UK
URN BIS/14/589 ISBN 978-1-78246-264-4 Crown Copyright © 2014