The ethics of research involving animals - Nuffield Council on ...
The ethics of research involving animals - Nuffield Council on ...
The ethics of research involving animals - Nuffield Council on ...
You also want an ePaper? Increase the reach of your titles
YUMPU automatically turns print PDFs into web optimized ePapers that Google loves.
T h e e t h i c s o f r e s e a r c h i n v o l v i n g a n i m a l s<br />
Stage 6: c<strong>on</strong>cept testing<br />
8.26 Typically, no more than a few candidate medicines for any given disease enter this stage. In<br />
Phase I <str<strong>on</strong>g>of</str<strong>on</strong>g> clinical trials, they are first tested in a limited number <str<strong>on</strong>g>of</str<strong>on</strong>g> healthy volunteers (see Figure<br />
8.3). <str<strong>on</strong>g>The</str<strong>on</strong>g> purpose is to determine how well the active ingredient is actually tolerated in humans<br />
and whether it has the desired effect, to obtain informati<strong>on</strong> about suitable dosage and to<br />
determine whether it has characteristics that would allow it to be developed into a medicine.<br />
Use <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>animals</str<strong>on</strong>g><br />
8.27 During the subsequent Phases II–IV, additi<strong>on</strong>al animal studies that aim to ensure the safety<br />
<str<strong>on</strong>g>of</str<strong>on</strong>g> the particular medicine and its applicati<strong>on</strong> are undertaken. For example, if a medicine is<br />
intended to be given to women <str<strong>on</strong>g>of</str<strong>on</strong>g> childbearing age, reproductive toxicology would be<br />
assessed in <str<strong>on</strong>g>animals</str<strong>on</strong>g> prior to Phase II studies (see paragraphs 9.22–9.23 and Box 8.4).<br />
Stage 7: development for launch<br />
8.28 If testing in healthy volunteers (Phase I) and a limited number <str<strong>on</strong>g>of</str<strong>on</strong>g> patients (Phase II) is<br />
successful then large-scale trials <str<strong>on</strong>g>involving</str<strong>on</strong>g> human volunteers are carried out (Phase III). Phase<br />
III trials involve between 1,000 and 5,000 patients, and provide the basis for the final decisi<strong>on</strong><br />
as to whether to c<strong>on</strong>tinue or aband<strong>on</strong> the project. <str<strong>on</strong>g>The</str<strong>on</strong>g> size and scale <str<strong>on</strong>g>of</str<strong>on</strong>g> Phase II and III<br />
studies make this stage the most expensive part <str<strong>on</strong>g>of</str<strong>on</strong>g> drug development (see Figure 8.3). 35<br />
Use <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>animals</str<strong>on</strong>g><br />
8.29 During clinical studies <strong>on</strong> humans, Phases I–III, a comprehensive set <str<strong>on</strong>g>of</str<strong>on</strong>g> safety tests in <str<strong>on</strong>g>animals</str<strong>on</strong>g><br />
c<strong>on</strong>tinues to be carried out. <str<strong>on</strong>g>The</str<strong>on</strong>g> project team that is developing the medicine liaises with the<br />
internal <str<strong>on</strong>g>ethics</str<strong>on</strong>g> committee and regulatory authorities, to define the tests that are required to<br />
ensure safety (see paragraphs 9.4–9.25).<br />
Vaccines and veterinary medicines<br />
8.30 <str<strong>on</strong>g>The</str<strong>on</strong>g> clinical development <str<strong>on</strong>g>of</str<strong>on</strong>g> vaccines may require further safety tests in <str<strong>on</strong>g>animals</str<strong>on</strong>g>, which are<br />
broadly similar to those required for human medicines. 36 <str<strong>on</strong>g>The</str<strong>on</strong>g> exact nature <str<strong>on</strong>g>of</str<strong>on</strong>g> these tests<br />
depends <strong>on</strong> the results <str<strong>on</strong>g>of</str<strong>on</strong>g> clinical trials. 37 <str<strong>on</strong>g>The</str<strong>on</strong>g> data required for a marketing authorisati<strong>on</strong> for<br />
a veterinary medicine c<strong>on</strong>cern pro<str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>of</str<strong>on</strong>g> efficacy and bioavailability <str<strong>on</strong>g>of</str<strong>on</strong>g> a product. 38 <str<strong>on</strong>g>The</str<strong>on</strong>g> scale<br />
and scope <str<strong>on</strong>g>of</str<strong>on</strong>g> the data provided are generally less comprehensive than for human medicines,<br />
although in some cases specific emphasis is given to certain areas. For example, in the case<br />
<str<strong>on</strong>g>of</str<strong>on</strong>g> food-producing <str<strong>on</strong>g>animals</str<strong>on</strong>g>, evidence is required <strong>on</strong> the potential for residues <str<strong>on</strong>g>of</str<strong>on</strong>g> new<br />
medicines to accumulate in food. 39 Bioavailability studies are similar to those undertaken for<br />
human medicines (see paragraph 9.24), although more-invasive muscle tissue samples may<br />
be taken in order to test for residues.<br />
35 <str<strong>on</strong>g>The</str<strong>on</strong>g> average length <str<strong>on</strong>g>of</str<strong>on</strong>g> clinical phases (c<strong>on</strong>cept testing and development for launch) is eight to twelve years and the average<br />
cost <str<strong>on</strong>g>of</str<strong>on</strong>g> clinical phases is £350 milli<strong>on</strong>, see <str<strong>on</strong>g>The</str<strong>on</strong>g> Associati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> the British Pharmaceutical Industry <str<strong>on</strong>g>The</str<strong>on</strong>g> Development <str<strong>on</strong>g>of</str<strong>on</strong>g><br />
Medicines, available at: http://www.abpi.org.uk//publicati<strong>on</strong>s/briefings/Dev_Medicines.pdf. Accessed <strong>on</strong>: 26 Apr 2005.<br />
36 <str<strong>on</strong>g>The</str<strong>on</strong>g> tests described in Chapter 9 may also apply to vaccines.<br />
CHAPTER 8 THE USE OF ANIMALS FOR RESEARCH IN THE PHARMACEUTICAL INDUSTRY<br />
37 <str<strong>on</strong>g>The</str<strong>on</strong>g> European Agency for the Evaluati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> Medicinal Products (1997) Note for Guidance <strong>on</strong> Preclinical Pharmacological and<br />
Toxicological Testing <str<strong>on</strong>g>of</str<strong>on</strong>g> Vaccines, available at: http://www.emea.eu.int/pdfs/human/swp/046595en.pdf. Accessed <strong>on</strong>: 26 Apr 2005.<br />
38 Veterinary Medicines Directorate (2002) Applicati<strong>on</strong> Form for a Marketing Authorisati<strong>on</strong>, available at:<br />
http://www.vmd.gov.uk/lu/forms/appform1a.pdf. Accessed <strong>on</strong>: 2 May 2005.<br />
39 See Veterinary Residues Committee Fact Sheet, available at: http://www.vet-residues-committee.gov.uk. Accessed <strong>on</strong>: 2 May 2005.<br />
143