Working to reduce the use of animals in research to reduce the use of . animals in scientific...

Working to reduce the use of animals in scientific research

2

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,

under the terms of the Open Government Licence. To view this licence, visit www.nationalarchives.gov.uk/doc/open-

government-licence/ or write to the Information Policy Team, The National Archives, Kew, London TW9 4DU, or

email: [email protected]


3

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


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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


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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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elivering our Commitment to Replace, Reduce nd Refine the Use of Animals in Research

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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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.

http://wellcomeimages.org/indexplus/result.html?wi_credit_line%3atext=%22Yirui%20Sun%22&%24%3dsort=sort%20sortexpr%20image_sort&%2asform=wellcome-images&_IXACTION_=query&_IXFIRST_=1&_IXSPFX_=templates%2fb&_IXFPFX_=templates%2ft&%24%20with%20image_sort=.

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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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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

1.0

2.0

3.0

4.0

5.0

Total

All other

Breeding

2012201120102009200820072006200520042003200220012000199919981997199619951994199319921991199019891988

0.5

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2.5

3.5

4.5

0

1.0

2.0

3.0

4.0

5.0

0.5

1.5

2.5

3.5

4.5

Millions of procedures

0

1.0

2.0

3.0

4.0

5.0

6.0

Procedures

Experiments

20122010

2005

2000

1995

1990

1985

1980

1975

1970

1965

1960

1955

1950

1945

0.5

1.5

2.5

3.5

4.5

5.5

0

1.0

2.0

3.0

4.0

5.0

6.0

0.5

1.5

2.5

3.5

4.5

5.5

Millions of procedures

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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

2000

1999

1998

1997

1996

1995

1,000

3,000

5,000

7,000

9,000

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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

17


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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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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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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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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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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(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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● 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


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

http://www.understandinganimalresearch.org.uk/policy/concordat-on-openness-on-animal-research

30


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


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


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


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


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


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


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


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


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


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


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


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


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

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