Submission to the House of Lords Committee on animals in scientific procedures 

Evidence from the Association of the British Pharmaceutical Industry    

What have been the strengths and weaknesses in the operation of the Animals (Scientific Procedures) Act since 1986; how do you consider that legislation on animal procedures needs to be changed?

The strengths of the animals (Scientific Procedures) 1986 Act  

1.      The 1986 Act provides what is considered to be one of the strongest and most comprehensive regulatory frameworks in the world for the control of animal research. The Act created a climate where optional animal welfare was recognised and valued.  

2.      The Act was designed to provide a flexible approach to the regulation and improvement of animal welfare which also ensures that the needs of researchers, in academia and government laboratories and in industry, who are required to carry out essential research using animals, are met. The 1986 Act sought to seek a balance between these needs of science, industry and the public against the need to limit animal suffering.  

3.      It has ensured that all of those involved in the use of animals in scientific procedures give attention to risk i.e. the costs to the animal, to the potential benefits, to the nature of the procedures and to the development of alternative approaches.  

4.      It provides strict criteria for the approval of Personal and Project Licences and for Certificates of Designation – a system which has helped to improve animal welfare. The Project Licence systems requires a detailed consideration of the balance between the benefits i.e. the justification for using the animals, against the costs to the animals in terms of the severity of the procedures to be used.  

5.      The Act led to the creation of Named Persons with specific legal responsibilities, and provided those Named with the authority to act or recommend change on behalf of the laboratory animals, within any corporate or university management structure, irrespective of management seniority. The requirement for review of Project Licence applications by the Named Animal Care and Welfare Officer (NACWO) and the Named Veterinary Surgeon (NVS) of the Establishment ensured that at least two people within every organisation acted as the “animals representative” in any discussion about housing, welfare and use.  

6.      From its inception, the Act positively modified the thinking and behaviour of researchers. Those with ambitions to improve animal welfare and use standards were provided with an important legal impetus, as were those who did not hold similar welfare-related ambitions, but who were obliged to recognise and install A(SP) Act-initiated improvements in animal use and welfare.  

7.      Through the development and use of Codes of Practice, it has established what the minimum expected standards are for housing and care, helping to harmonise and install “best practice” across all establishments.  

8.      It has enabled comprehensive and structured training programmes to be developed.  

9.      It enabled ongoing dialogue with the Home Office Inspectorate on the design of animal procedures and on developments on reduction, refinement and replacement.  

10.  It has allowed the UK to remain compliant with (and in many cases exceed) European legislation on animal research, including EU Directive 86/609, and the European Convention on the Protection of Vertebrate Animals (ETS 123).  

What are the weaknesses in the operation of the animals (Scientific Procedures) Act since 1986, and how do you consider that legislation on animal procedures needs to be changed?  

11.  It is considered that an escalation in the bureaucracy of the operation of the Act has led to increasing complexity of the system, a certain inflexibility of approach and a resultant delay in the approval system. This increase in time-consuming administrative processes and the demand, by the Home Office, for the provision of greater detail in the project and personal licence system has caused logistical difficulties in many organisations (large and small). This increasing complexity has led to delays in the time taken before research could be initiated. Of concern to the Association is the belief that this approach and the increased regulatory burden has not necessarily resulted in any benefits to animal welfare.  

12.  The Association recognises that one of the factors contributing to the delays in the granting of licences has been the occasional pressure on the support provided by the Animals, Bylaws and Coroners Unit. The Association is pleased that there have been moves for the provision of additional administrative support by the Home Office in this area, a recent increase in the Inspectorate and a move towards greater use of IT.  

13.  The Association does not consider that any changes to the legislation per se are required at present. Although there have already  been a number of recent changes to the implementation of the Act, including the introduction of a formal Ethical Review Process at each Establishment, we consider that the major weaknesses in the current operation of the Act can be addressed through amendments to its implementation. What is needed is a continued effort by the Home Office to identify ways of simplifying what has become a very complicated project licensing system and, whilst maintaining animal welfare, to reduce the administrative burden currently associated with the operation of the Act.  

14.  The proposed introduction of Freedom of Information (FOI) legislation by the Government has clearly identified what may be considered a weakness in the operation of the Act. The UK is unique in having an animal research licensing system which requires extremely detailed accounts of research plans to be provided to government. No other country requires such detailed information to be given. At the time that the Animal (Scientific Procedures) 1986 Act was framed, the pharmaceutical industry was asked to provide such detailed information in licence applications on the legally binding understanding that it would be held in confidence. The inclusion of Section 24 assured this. Irrespective of the potential impact on commercial confidentiality, the industry has not been reassured that the proposed exemptions provided in the FOI legislation will provide an equivalent level of protection to the personal safety of researchers in the current climate. We have therefore called upon the Government to maintain Section 24 for the time being as the implementation of FOI goes forward.  

15.  We do recognise, however, that it is important for the public to have a greater understanding of the nature of, and need for, animal research conducted in the UK . The industry has therefore discussed with the Home Office the possibility of companies providing with each project licence application an account, specifically for disclosure, that could help inform interested parties about the nature of the research to be conducted under the licence and the standards of animal care and welfare that will be employed. We believe that this will facilitate openness in a more meaningful way than would be the case if complex information in project licences were disclosed.  

16.  A number of the issues above have been discussed within Working Group 3 of the Prime Minister’s Pharmaceutical Industry Competitiveness Task Force (PICTF) which sought to identify how the animal scientific procedures licensing processes could be made more efficient without any negative effects on animal welfare standards. The review was initiated in response to concerns raised by the research community (industry and academia) that the increasing complexity of the licensing system was forcing researchers to place specific projects outside the UK in order to have them conducted in a timely and cost-effective manner, a situation likely to threaten future inward investment. Discussions with the Home Office on the outcome of PICTF have assisted in its ongoing review of how resources can be used to best effect. A summary of the initial outcomes of the PICTF initiative is appended. (Attachment 1).  

What scientific developments and changes in public attitudes have occurred relevant to animal procedures since 1986; how have researchers and regulators responded to such changes; and do you consider that their response has been appropriate?  

What scientific developments have occurred relevant to animal procedures since 1986?  

17. There have been major scientific developments in molecular biology since 1986 which have had, and will continue to have, a significant impact on the use of animals in scientific procedures. The sequencing of the human and mouse genomes and the opportunity to identify genes involved in the disease process has led to the possibility of new areas of research which, however, has resulted in an increased use of animal procedures. The development of genetically modified and transgenic animal strains have led to the establishment of new models of diseases, and the possibility of new tests for the safety assessment of chemicals and potential new medicines.  

18.  At the same time, there has been a significant increase in the use of cell culture and in vitro techniques over the last 15 years including the use of human tissue (where available), together with a considerable increase in the use of high throughput robotic techniques. These techniques, based on a greater understanding of the disease processes at cellular level and the use of cloned human receptors, has enabled the pharmaceutical industry to screen very large numbers of compounds very rapidly, allowing a better and quicker selection of potential medicines to take place before any further development (which may involve subsequent testing in animals) occurs.  

19.  This has led to a considerable reduction in the numbers of animals used per new candidate medicine going into development, which is likely to be less than 20-30% of the number used in 1986.  

20.  There have been major technological developments since 1986 to introduce refinement into experimental work e.g. the use of telemetry for permanent monitoring of an animal and sophisticated surgical techniques which allow repeated blood sampling to take place without disturbing the animal.  

21.  Other scientific developments have also led to improvements to housing and husbandry, in the identification of alternatives to animal use, or in the use of other species. There have also been major developments since 1986 in experimental design, in the application of statistics and in the refinement of procedures in general. Developments in the science of animal welfare and veterinary medicine since 1986 have also led to changes in animal procedures.  

22.  We consider that the existing regulatory controls on animal procedures apply as well to the current scientific environment and to the scientific developments described above as it did to the environment at the time of the Act’s implementation in 1986. The requirements for a cost benefit analysis to be carried out and the need for an assessment of what alternatives might exist before research is permitted remain in place. The regulatory systems in place within the Act are appropriate for all aspects of animal research. Nevertheless, researchers in the UK have responded positively to all proposals put forward by the Home Office which seek to improve the legislation.  

23.  The general public in the UK have long been concerned for the welfare of all animals used by humans. We acknowledge that there has been some public concern over the use of animals in research, over welfare standards and over animal suffering.  The research community has responded to these concerns through its increased focus on animal welfare before and during animal procedures. Many opinion polls have shown that the public’s understanding of the regulatory procedures in place for animal research is somewhat limited and the Association believes more does need to be done to explain to the public why the research is needed and that we have in place in the UK the most comprehensive legislative system in the world. The recent increase in the number of Inspectors (strongly advocated by the industry for some time) was a positive development by the Home Office, which we believe could help maintain public confidence in the system.  

24.  Opinion polls have also tended to suggest that the public recognises the need for animal research in the development of new medicines and vaccines and in the search for novel therapeutic approaches to untreated diseases and disorders. Although they may prefer the research not to be done, there is an acceptance of its necessity. It is acknowledged that, with a few notable exceptions, the research community has not been proactive in seeking to communicate with the public on the need for such animal research. As many of those giving evidence to this inquiry will have commented, the increasing extremism of animal rights activist organisations has created an environment in the UK that inhibits researchers talking publicly about their studies. There have been organised campaigns of harassment and intimidation of individual researchers and organisations involved, either directly or indirectly, in animal research. The ABPI is pleased that the Government has responded to these threats to scientists and suppliers and has sought to establish an effective legislative framework to protect researchers. With the right environment being developed with the support of government and the marginalisation of the more extreme animal rights organisations, it is anticipated that the research community will attempt to play a greater role in influencing public attitudes.  

What are the current effective alternatives to animal procedures; and hat alternatives to animal procedures might be developed?  

25.  Under the Animals (Scientific Procedures) 1986 Act, an animal can only be used in a scientific procedure if it can be shown that there are no valid alternatives. The pharmaceutical industry has invested considerably in the development of alternative, non-animal procedures in the discovery and safety assessment of potential new medicines. The use of animals is costly and time-consuming.  

26.  The term “effective alternative” does, however, have different meanings within the early discovery screening phase and the regulatory toxicology/ safety assessment phase of medicines development.  

27.  In the context of regulatory toxicology and the safety assessment of pharmaceuticals, the term “effective alternative” is taken to mean a procedure accepted by regulatory authorities as producing reliable and meaningful data without using animals. Currently, the only such alternatives are in vitro tests for the genotoxic potential of drugs, for skin corrosive potential and for eye irritant potential. For the myriad of other assessments of toxic potential, metabolic fate and the pharmacokinetics that are required for the approval of a new drug, there are no current “effective alternatives”. The reasons for this are well known – as yet it is impossible to model adequately in the test tube or in a computer, the many and complex factors that operate in the whole animal to determine whether, and at what dose, a drug may exert adverse effects in vivo and what such effects may be.  

28.  All medicines have to be tested for their safety before patients are exposed to them. This is a regulatory requirement of all governments. There are comprehensive regulatory controls on the use of human volunteers in early stage clinical trials and their use is only allowed after there has been a detailed review by the regulatory authorities of all available data, including safety data from animal test studies.  

29.  In this field of regulatory toxicology, any alternative to animal use has to be validated before the regulatory authorities can accept them instead of animal-based studies. It is probable therefore that alternatives will not be acceptable for some time in regulatory toxicity testing.  

30.  In contrast to the situation in regulatory toxicology, the use of alternative procedures for early screening in drug discovery has expanded greatly, and in the majority of cases, in vitro systems have virtually replaced animal procedures in screening new compounds for receptor-based biological activity, predicted to give rise to useful pharmacological actions. This has been largely due to advances in molecular biology and an understanding of drug action at the level of individual protein targets. There have been major advances in the use of high throughput in vitro assays, coupled with the use of cell and tissue culture systems and computational chemistry in the early evaluation of potentially useful compounds.  

31.  Nevertheless, in many, if not most cases, confirmation of the expected pharmacological effect still requires the use of an animal model. For early toxicology and metabolism screening, in vitro systems which could not be used for definitive toxicity assessment are used in early screening to help “weed out” the most potentially toxic from a group of related candidates for drug development. In the same way, these in vitro techniques are now widely used in the industry to gain an early assessment of likely absorption and the metabolic fate of the potential drug. Overall, these developments have benefited animal welfare by reducing the overall number of animal procedures required for each potential new medicine.  

32.  In the future, the development of alternatives in pharmaceutical toxicology will focus increasingly on systems for assessing drug effects at the level of individual gene and protein expression. The industry is also seeking to develop “humanised” cell systems, cloning into cell lines genes for key enzymes and other important determinants of toxicology. Research will also continue into understanding the molecular mechanisms by which drugs exert their toxicity. This will be essential for any future assessment of the significance of in vitro data in terms of in vivo responses, no matter how sophisticated the in vitro system may be.  

How do you consider that demand for animal procedures will develop in the future; and how should the regulatory system respond?  

33.  It is impossible to predict how the demand for animal procedures will develop in the future. On the one hand, there has been a general downward reduction in the number of animal procedures as new techniques in experimental design are developed leading to the need for fewer animals. This trend may continue as scientific developments are taken forward which could lead to the introduction of further non-animal methods. At the same time, there are many factors that are likely to lead, in the short to medium term, to an increase in animal numbers used. Within the pharmaceutical industry, following the completion of the human genome there may be an increase in animal use as researchers try to understand the specific functions of genes and how these genes are linked to specific diseases and disorders.  

34.  This research will lead to the identification of new targets which will be used in the identification of potential new medicines. Such research, using genetically modified and transgenic animal modes of human disease, has already led to major developments in the understanding of a number of medical conditions in which research has previously been very difficult. It should also be noted that these genetically modified animal models of disease may lead to other improvements in animal welfare, as they are able, in some circumstances, to reduce the possible animal suffering associated with other experimental approaches such as the use of surgical techniques.  

35.  Through the development of in vitro methods by the pharmaceutical industry, far fewer animal procedures are used today in the identification of each possible new medicine than ever before. However, there are still numerous unmet medical needs for which further research is essential. The UK ’s strengths in biomedical research are recognised internationally and it is one of the main reasons why the pharmaceutical and biotechnology industry sectors choose to carry out its research in the UK . As both academic and industrial biomedical research increases in the UK , and research is conducted in new areas of disease, it is inevitable that the number of regulated animal procedures will increase.  

36.  There are many other factors that may impact upon the demand for animal procedures in the future:  

Human health and safety expectations  

37.  As a result of public demand for increased safety testing of, for example, GMO-based products, chemicals in the environment and for a greater understanding of disease outbreaks such as Foot and Mouth Disease, animal procedures are likely to increase. Responding to European legislation (through the EU White Paper on Chemicals for example) may lead to the increase in animal use in the testing of chemicals in the environment and workplace.  

Regulatory safety assessment of medicines  

38.  The detailed discussions that have taken place between industry and the regulatory authorities (of Europe, USA and Japan) through the 1990s (and which are continuing) through the International Conference on Harmonisation (on technical requirements for production registration) led to an initial and substantial reduction in animal procedures as obvious areas of unnecessary and duplicative testing were identified. However, as the regulatory authorities strive to ensure that patient safety is paramount, the regulatory processes are likely to demand, for the foreseeable future.

Attachment 1  

Pharmaceutical Industry Competitiveness Task Force (PICTF)  

Outcomes of discussions on the operation of the Animals (Scientific Procedures) Act, 1986  

Introduction
Working Group 3 (Science Base and Biopharmaceuticals) of the PICTF conducted a review of the Animal Scientific Procedures licensing processes with the aim of promoting animal welfare by using existing resources to best effect.  

The review was prompted by concerns raised by both the pharmaceutical industry and the academic scientific community about the time taken over administration of the licensing system. Not only did this cause delays to research projects, but it was threatening to affect laboratory animal welfare.   It was recognized that the recent increase in bureaucracy was adding significantly to the administrative burden placed on animal care and welfare staff, so that increases in the efficiency of the regulatory process would permit them to devote more time to animal welfare duties.  

A subgroup comprising members from industry, academia, the Department of Trade & Industry, the Home Office and the Research Defense Society was set up under the Chairmanship of Lord Sainsbury, Minister for Science and Innovation, to identify ways in which the regulatory system could be made more efficient without any negative effects on animal welfare standards.  

Initial outcomes
·        The Home Office will seek an increase in the Animal Scientific Procedures Inspectorate, a
     boost to existing resources which industry considers will impact beneficially on
     the efficiency of the current licensing system.  

·        The Chief Home Office Inspector has provided a redefinition of the aims of the Ethical Review Process (ERP), through presentations, a circular to Certificate Holders and publication on the Internet. The objective is to minimise the bureaucracy inherent in ERP and to refocus efforts on effective implementation of the 3Rs throughout the duration of a licence and its associated protocols. It is considered that an efficient local ERP should in each case be able to complete its task within two weeks of receiving a written application for consideration.  Further advice will be made available following the current HO review of ERPs (completion date planned for 3Q, 2001). The Association of the British Pharmaceutical Industry (ABPI) has offered to hold a forum for this communication.  

·        The Home Office has agreed to operate to a target time of seven 7 weeks for the processing of project licence applications including the time taken for consideration by the inspectorate. This will operate on a “stop the clock” basis so that time taken to seek responses from the applicant will not be included. Some flexibility will be needed as complex applications may take longer to allow for Home Office internal consultations.  

·        In order to facilitate the administrative aspects of licensing, the Home Office is finalising an IT strategy for implementation in the short term. The electronic submission of project licences will be a medium term aim.  

·        The revised project licence form and associated guidelines for completing the form are now available on the Home Office website and should be used.  

·        HO have communicated that Certificate Holders may nominate a deputy so that applications can be signed when the Certificate Holder is unavailable.  

·        The Home Office has clarified that a movement document is not needed if the movement of animals is already authorised by the Home Office.  

·        The Home Office will consider proposals when available (end 3Q, 2001) from the Expert Group on Efficient regulation on  revisions to the project licence application form designed to focus more in animal welfare and less on unnecessary administration and bureaucracy.

·        The Home Office will note and seek to collate information on the most common difficulties and mistakes encountered by applicants when applying for a project licence. From this it will seek to advise on what further training, or advice for project licence holders, might be of assistance. At the same time project licence holders applying to the Home Office will seek to ensure in future that applications are correctly and fully completed at the onset.

·        The Home Office will consult the Accrediting Bodies to review the content of Module 5 in the light of the above findings.  

·        The Home Office will consult the Accrediting Bodies on the Home Office requirement for original training certificates to be provided before a licence is issued.  

·        The next Certificate Holders’ circular will canvass views on electronic circulation of these letters. This will enable Certificate Holders to provide those working under the Act with the circulars more efficiently.  

·        The Home Office will publish the advice that European-accepted accredited training  (ie to FELASA standard) will be accepted when combined with Module 1 of an UK Accredited course for experienced European researchers applying for a personal licence.  

·      The research community will identify ways of streamlining the ERPs for secondary availability.  

·        The Home Office will review the processes for handling secondary availabilities in order to identify ways of streamlining the processes especially in situations where 2 inspectors are involved.  

§         The Home Office has asked the APC to conduct a review of Schedule 1 euthanasia. It is hoped that this will mean that projects requiring the use of ex-vivo tissue from neonates will not need a project licence if no other animal work is involved.  

·        The rationale for the timescale of  HO consultations will be explained and whenever possible a 60 day period will be allowed for responses. Consultations around new policies will include a call for comments on the resource implications of implementation.

Association of the British Pharmaceutical Industry (ABPI)