Ethics of Research involving animals
Regulations requiring the use of animals
13.48 So far, we have concentrated on regulation that authorises and prescribes the ways in which animals can be used in research, seeking to minimise possible harm. As we have said (see paragraphs 8.22 and 9.4), animal research is also undertaken because regulations at both the national and international levels stipulate that medicines, vaccines and chemicals for use in agriculture, industry, food and household products must be tested for efficacy and safety. Some regulations require that animals must be used, whereas others merely require that tests must be undertaken according to best practice, which is often interpreted as requiring the use of animals. Companies and institutions within countries such as the UK, which are members of many different international organisations and operate in international markets, are also subject to overlapping legislation and guidelines.
Testing of medicines
13.49 In the UK, new medicines must meet the requirements of the Medicines Act 1968 in order to be licensed. The Act states that a medicine must demonstrate that it is safe, effective and of high quality and this is usually interpreted as requiring testing on animals.43 EU legislation, particularly Directive EC 2001/83 on the Community code relating to medicinal products for human use, now takes precedence over the Medicines Act, which has been amended several times to align with new requirements. The Directive requires that all new prescription medicines are studied in animals before they are tested in humans. It states that before a new medicinal product can be marketed in the EU, the producer shall obtain authorisation by the appropriate competent authority (either the national regulatory agency or the EMEA). Article 8 (3) stipulates that an application to one of these agencies shall include: ‘Results of: physico-chemical, biological or microbiological tests, toxicological and pharmacological tests, [and] clinical trials’. The exact requirements, standards and protocols for both animal and non-animal tests are described in detail. For example, singledose toxicity shall be assessed by the following protocol:
‘The acute toxicity test must be carried out in two or more mammalian species of known strain unless a single species can be justified. At least two different routes of administration shall normally be used…’44
13.50 In other countries, medicines are licensed through equivalent regulatory authorities such as the Food and Drug Administration (FDA) in the US and the Ministry of Health, Labour and Welfare in Japan. The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) coordinates the pharmaceutical regulatory authorities of Europe, Japan and the USA (see paragraph 12.8). It aims to harmonise guidelines on quality, safety and efficacy in its member countries. Certain of its safety guidelines specify that animal research should be performed.45
Testing of chemicals
13.51 Primary UK legislation requiring the testing of chemicals includes the following: the Health and Safety at Work Act 1974, the Consumer Protection Act 1987 and the Food Safety Act 1990. These acts mostly implement the provisions of corresponding EU directives. The OECD has harmonised the testing of new chemical compounds across member countries, including the UK, USA, Japan, France and Germany. Certain OECD testing guidelines require the use of animals.46 These are a collection of methods developed by OECD member countries for identifying the hazards of chemical substances (see paragraphs 9.5 and 12.8).
Differences in international test guidelines
13.52 There is some variation in the data and methods that different national regulatory authorities are willing to accept, when assessing, for example, the safety or efficacy of new medicinal or agrochemical products. Although organisations such as ICH and OECD aim to achieve a certain degree of harmonisation, it is often the case that a single chemical that is marketed in a number of countries might need to be tested several times for toxic effects, in order to satisfy national standards. For example, during the Working Party’s fact finding meeting with experts from the Home Office, reference was made to a licence that had been granted for vaccine trials on primates involving procedures of substantial severity. This type of animal use typically involves the immunisation of animals with a candidate vaccine, and subsequent exposure to the infective organism. A range of different doses of the vaccine are then administered, to assess its efficacy and safety. The test requirements and methods are generally set at European or higher supra-national levels and usually require that the test be continued until it becomes clear that the animals have not survived the disease. The Home Office took the view that trials should be stopped at an earlier stage if the scientific objective can be achieved. At the time of writing, the matter was being discussed with relevant stakeholders and regulators to encourage the development and adoption of such measures, and to identify earlier endpoints for studies.47 However, different conceptions of what qualifies as sufficient scientific evidence for the safety and efficacy of new chemicals, different frameworks for liability and compensation, as well as general political disagreements between nations, all contribute to complications in the harmonisation of laws and guidelines on animal testing. We continue the discussion on the international context of animal research in paragraphs 15.84–15.87.
Footnotes43 See Animals in Medicines Research Information Centre, available at: http://www.abpi.org.uk/amric/basic5.asp. Accessed on 5
May 2005.
44 EU Directive EC 2001/83, Annex 1, Part 3 Performance of Tests: Toxicity.
45 See The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for
Human Use (ICH): Safety Guidelines, available at: http://www.ich.org/UrlGrpServer.jser?@_ID=276&@_TEMPLATE=254.
Accessed on: 5 May 2005.
46 See OECD (1993) Chemicals Testing: OECD Guidelines for the Testing of Chemicals – Sections 1–5, available
http://www.oecd.org/document/22/0,2340,en_2649_34377_1916054_1_1_1_1,00.html. Accessed on: 4 Apr
47 This is consistent with the current general approach of the Home Office, which requests that a trial should
signs occur that reliably predict the death of the animal. If such signs manifest themselves, the animal is
killed, instead of dying from the disease, see Home Office (2003) Animals (Scientific Procedures) Act 1986:
Conduct of Regulatory Toxicology and Safety Evaluation Studies, revised June 2003, available at:
http://www.homeoffice.gov.uk/docs2/regtoxicologydraftrevision4_03.html. Accessed on: 5 May 2005.