Ethics of Research involving animals
Use of animals in current pharmaceutical research and development - continuation III
8.25 Potential new medicines are first tested on small groups of healthy human volunteers, and then on progressively larger groups of patients.34 These tests are organised into four consecutive trials, Phases I–IV (see Figure 8.3). Experimental medicine has enlarged the application of existing clinical tests that are used in these studies. They include advanced blood and tissue diagnostics, and imaging techniques, such as MRI or PET scanning (see paragraph 5.12 and Box 11.1).
Figure 8.3
Stage 6: concept testing
8.26 Typically, no more than a few candidate medicines for any given disease enter this stage. In Phase I of clinical trials, they are first tested in a limited number of healthy volunteers (see Figure 8.3). The purpose is to determine how well the active ingredient is actually tolerated in humans and whether it has the desired effect, to obtain information about suitable dosage and to determine whether it has characteristics that would allow it to be developed into a medicine.
Use of animals
8.27 During the subsequent Phases II–IV, additional animal studies that aim to ensure the safety of the particular medicine and its application are undertaken. For example, if a medicine is intended to be given to women of childbearing age, reproductive toxicology would be assessed in animals prior to Phase II studies (see paragraphs 9.22–9.23 and Box 8.4).
Stage 7: development for launch
8.28 If testing in healthy volunteers (Phase I) and a limited number of patients (Phase II) is successful then large-scale trials involving human volunteers are carried out (Phase III). Phase III trials involve between 1,000 and 5,000 patients, and provide the basis for the final decision as to whether to continue or abandon the project. The size and scale of Phase II and III studies make this stage the most expensive part of drug development (see Figure 8.3).35
Use of animals
8.29 During clinical studies on humans, Phases I–III, a comprehensive set of safety tests in animals continues to be carried out. The project team that is developing the medicine liaises with the internal ethics committee and regulatory authorities, to define the tests that are required to ensure safety (see paragraphs 9.4–9.25).
Vaccines and veterinary medicines
8.30 The clinical development of vaccines may require further safety tests in animals, which are broadly similar to those required for human medicines.36 The exact nature of these tests depends on the results of clinical trials.37 The data required for a marketing authorisation for a veterinary medicine concern proof of efficacy and bioavailability of a product.38 The scale and scope of the data provided are generally less comprehensive than for human medicines, although in some cases specific emphasis is given to certain areas. For example, in the case of food-producing animals, evidence is required on the potential for residues of new medicines to accumulate in food.39 Bioavailability studies are similar to those undertaken for human medicines (see paragraph 9.24), although more-invasive muscle tissue samples may be taken in order to test for residues.
Stage 8: launch phase
8.31 At this stage, the data from all of the pre-clinical and clinical studies are collated and sent to the regulatory agencies (see paragraphs 9.4 and 13.49–51). The average time for regulatory approval is 1.5 years.
Use of animals
8.32 There is usually no animal use at this stage.
Footnotes33 The European Agency for the Evaluation of Medicinal Products (1997) Note for Guidance on Preclinical Pharmacological and
Toxicological Testing of Vaccines, available at: http://www.emea.eu.int/pdfs/human/swp/046595en.pdf. Accessed on: 26 Apr 2005.
34 See ABPI (2003) Clinical Trials - Developing New Medicines, available at:
http://www.abpi.org.uk/publications/briefings/clinical_brief.pdf. Accessed on: 26 Apr 2005.