Nuffield Council on Bioethics / Home

Ethics of Research involving animals

Use of animals

8.34 Limited animal use may be required for new indications, new formulations or in studies of possible adverse effects in patients. However, there is much reliance on archived animal and human testing data.

Vaccines

8.35 An exception to limited use of animals at this stage occurs in vaccine testing. Immunisation is a very cost-effective public health intervention and billions of doses of vaccine are administered each year for the prevention of a range of diseases.40 Relatively large numbers of animals are used for toxicity testing of batches of these vaccines. This is because the exact composition and properties of many biological products are very difficult to control and may alter after production.41 Continuous safety and efficacy testing of production batches of vaccines is therefore carried out.42

8.36 Depending on the type of test, there may be serious welfare implications. For example, if death is the required endpoint, or if it is the most convenient stage for reliable observation, then it may be used, subject to regulatory approval. While the terminal stages of a lethal endpoint may not involve much, if any, suffering as the animal may be comatose, the suffering that may have taken place beforehand can be substantial and may have involved symptoms such as inappetence (lack of appetite), malaise, convulsions or paralysis (see also Box 8.5).

Box 8.5: Examples of animal suffering in the context of quality control of vaccines for human use* Tetanus potency test Batches of tetanus vaccine are tested for potency in mice or guinea pigs. The standard method involves testing a new vaccine against a reference vaccine at three different concentrations. It has been estimated that 66–108 animals are usually used for each test. The animals are administered with the vaccine under the skin and four weeks later with a single dose of tetanus toxin. This dose could be lethal or paralytic. Control animals (that receive no vaccine) and those animals that are unprotected because the test vaccine they receive is unsuitable or is at an ineffective concentration suffer paralysis and death. Diptheria (absorbed) potency test Guinea pigs are immunised with test samples of diphtheria vaccine, and are subsequently infected with diphtheria bacteria four weeks later. In the EU, both lethal and non-lethal amounts of the bacterial toxin are permitted for this test and the endpoints are death or skin inflammation respectively. At least three dilutions each of the test vaccine and a reference vaccine are used, together with one untreated control group. A minimum of 70 animals is used to test each vaccine batch and both methods cause severe pain and distress for those animals that are unprotected (see above). There is no agreement on whether the lethal or nonlethal methods cause greater suffering. * See The Associate Parliamentary Group for Animal Welfare (2005) The Use of Animals in Vaccine Testing for Humans, available at: http://apgaw.org/userimages/Vaccinetesting.pdf Accessed on: 26 Apr 2005.

Footnotes

40 See World Health Organization (2003) Vaccines, Immunization and Biologicals – Statistics and Graphics, available at:
http://www.who.int/vaccines-surveillance/StatsAndGraphs.htm. Accessed on: 26 Apr 2005.
41 For example, the reactivation by mutation of inactivated viruses needs to be monitored and assessed.
42 The recent report by the Associate Parliamentary Group for Animal Welfare on vaccine testing describes why such quality control is required, the animals that are used, the pain and distress that they experience and the current use, and prospects for,
Replacement, Reduction and Refinement. See The Associate Parliamentary Group for Animal Welfare (2005) The Use of Animals in Vaccine Testing for Humans, available at: http://apgaw.org/userimages/Vaccinetesting.pdf. Accessed on: 26 Apr 2005.