ATLA 41, 325–327, 2013
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Editorial The Labelling of All Medicinal Products as Dependent on Animal Research would be a Minefield to be Avoided At All Costs Michael Balls
The Medicinal Labelling Bill should be rejected by Parliament, as ill-conceived and an unworthy and transparent attempt to promote laboratory animal experimentation
On 24 October 2011, a short debate took place in the House of Lords, on what plans the Government had to change the regulations governing experiments on animals, in compliance with the requirements of the new EU Directive, Directive 2010/63/EU.1 During the debate, Professor Lord Winston said, “There is a case for having legislation to make it clear that a particular drug has only been possible for human consumption because of animal testing”. This, he said, “Could be stamped on the packet, rather like a [notice on a] cigarette packet”. This made me wonder what manufacturers would need to put on the leaflet inside the drug packet, to explain what the label on the outside of the packet actually meant, and I suggested in an editorial2 that transparency and total honesty would require something like this:
On 13 May 2013, the Medicinal Labelling Bill,3 a Private Members Bill introduced by Lord Winston, received its First Reading in the House of Lords. The aim would be to require “a declaration relating to the use of animal research to be placed on medicinal products’ labels”, and the Bill specifies that: 1.1. All medicinal products’ labels shall state that the product has been produced as a result of research on animals. This label will be required on the individual packet of each medicinal product sold within the United Kingdom. 1.2. A pharmaceutical company is guilty of an offence if it fails to label its products. 2.
“Testing on animals: Despite the fact that thousands of animals were used in the discovery and development of this product, no guarantee can be offered that it will work or be sufficiently safe in your case. This is because animals and humans are significantly different in terms of their physiology, pathology and responses to drugs, so laboratory animals can usually provide only poor models of human diseases and responses to possible therapies. In addition, the animal tests conducted took little or no account of human genetic variation, of differences in human geographical, societal, occupational or lifestyle factors, of the simultaneous incidence of other diseases, or of the concurrent use of other drugs. It is for these reasons that it must be admitted that there are insuperable uncertainties about the efficacy of the product and the risk of potentially serious side-effects of many kinds.” Lord Winston was invited to reply to my comments, but chose not to do so.
In this Act, “medicinal products” means any drug, medicine or vaccine as listed in the British National Formulary whether prescribed or bought over the counter, where animals have been used at any stage of the development, production or manufacture of the medicinal product, or where animals have been used to assess its safety or efficacy; and “animals” refers to any animal, other than human, which is a vertebrate.
The procedure is that the First Reading in one of the Houses of Parliament is a formality, followed by a Second Reading debate, a Committee stage, and a Third Reading debate, after which a surviving bill is passed on to the other House of Parliament, in this case the House of Commons, for a similar series of stages. The Second Reading took place on 25 October 2013,4 when Lord Winston opened the debate, to propose that the Bill be read for a second time. This was a somewhat rambling pro-vivisection
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speech, which alone could provide the basis for a long series of editorials. He said, for example (with my observations in parentheses): that animal research in the UK is considerably under threat (but the number of procedures increases every year); that the pharmaceutical industry in this country is under considerable threat, and it is very sad that Pfizer has moved offshore its research establishment at Sandwich (but I have never seen it claimed that this departure was due to opposition to Pfizer’s experiments on animals); that animal experimentation is strictly regulated by the Home Office, and that Imperial College, where he works, has a very large animal facility (but he did not mention the controversy over revelations about unacceptably poor animal practices there); and that cell culture [as an alternative] “does not work because it does not use the intact animal” (but it is the human which is overwhelmingly the object of pharmaceutical research, and much is being achieved, as human in vitro to human in vivo extrapolation is found to be more reliable than animal in vivo to human in vivo extrapolation). One of the purposes of Lord Winston’s proposal is to encourage openness, which is laudable, but that would require much more than a small phrase on the labelling on a packet of medicines. That point was picked up by Lord Willis, chairman of the Association of Medical Research Charities (AMRC), who said that, “Simply having a message on the packet is not enough. You need to know what is behind it”. He was also concerned that, “Since many people do not take the drugs prescribed for them, the proposed labelling might encourage more of them to say, ‘I will not take that, because it has been tested in animals’”. Referring to opinion polls on public attitudes to using animals for research, he said that more and more of those questioned want to know more, before they are willing to give their support for such research. Lord Turnberg, former chairman of the NC3Rs, and an adviser to AMRC, supported Lord Winston’s initiative, but said that “neither the pharmaceutical industry nor basic scientist were at all resistant to the idea of replacing or reducing the numbers of animals”. He also emphasised that it is the regulatory bodies that insist on animal testing. He said that the vast majority of people are somewhere in the middle between the pro- and anti-vivisectionists, and “want to be assured that systems are in place to minimise suffering and that animal use is essential for the discovery and use of new cures for their ills”. Baroness Wheeler, from the Opposition Front Bench, was more cautious. She accepted the need for greater understanding among the general public, but felt that clearer evidence was needed “on what the impact on public opinion and awareness [of drug packet labelling] would be, and how any
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negative impacts on patients and their health would be addressed”. She also stressed the need for taking account of the requirements of Directive 2010/63/EU and their transposition into UK law. Baroness Jolly, the Coalition Government Minister, emphasised the Government’s commitment to reducing the use of animals in research and to the Three Rs, and said that it was pressing ahead with a domestic programme, an international programme, and “a programme to promote understanding and awareness about the use of animals where no alternative exists”. She explained that the labelling of medicines is governed by Directive 2001/83/EC, which does not require a statement of animal research. Also, it is important that the regulations permit a pharmaceutical company to market a product in all EU Member States, so there is no opportunity for specific UK labelling. She argued that the interests of patients were of particular importance, and that there would be a risk that healthcare professionals would need to take time to explain any labelling to patients and “reassure them about the safety of the medicine and the rationale for prescribing a product”. In addition, there would be difficulty in defining “the extent of animal research that would require relevant labelling”, which might require a timescale or threshold to be used, and a decision about proportions of active ingredients and excipients. She concluded that, while she agreed that it is important to explain the need for and value of research on animals, she “could not share the view that the labelling of medicines is the right vehicle to achieve those ends”, and the Government could not support the Bill. The Bill was given a Second Reading, and now proceeds to consideration by a Committee of the Whole House of Lords. It will be interesting to see what happens to the Bill at the Committee stage and Third Reading in the Lords, and, if it survives, what will happen to it in the Commons. This all reminds me of the kinds of situation which have arisen in the past, and the arguments which have been rehearsed, over and over again. The labelling of products is a minefield, into which only the foolish tread. In the animal testing arena, this first arose when cosmetic products began to be labelled “cruelty-free” and “not tested in animals”. This led to all kinds of problems for consumers, retailers and manufacturers, since the meaning of these terms was not clear, and they were often used cleverly, if not dishonestly.5 Similarly, it is not good enough to merely say “tested in animals” — what animals, how many of them, what procedures were applied and why, what steps were taken to minimise numbers and avoid suffering, what was the outcome, and how did it contribute to the decision to accept the marketing of the product for human use?
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Lord Turnberg was right. Many people reject the dogmatic pro-vivisection and anti-vivisection arguments, and place themselves in the middle ground between them, accepting that some use of animals is essential until relevant and reliable alternative methods can be developed and validated, which make such use unnecessary. A lot of effort is being invested in trying to do just that, and the old-fashioned ploys of the animal research liberationists would convince no one who knows anything about the subject. The views of members of the public are likely to differ widely according to particular situations, such as whether the animals used are dogs and monkeys, or rats and mice, or whether the procedures applied cause minimal or substantial suffering. Understanding Animal Research are currently conducting the Big Animal Research Debate in universities, where the motion is that This House would ban all forms of animal research.6 Frankly, that motion is too sweeping, and its rejection, wherever it occurs, will make no useful contribution to a very important debate, which needs to be treated more seriously. However difficult it may be, it is necessary to be discriminating — to carefully look at specific circumstances, in order to decide what could be considered essential, and therefore scientifically and morally defensible, and what could not. That is what Russell and Burch argued when they presented the Three Rs, and they rejected the idea that experiments on other vertebrates would be useful, just because they have some similarities to ourselves. If that was true in 1959, it is much more true today, since a vast array of non-animal procedures, which can safely and ethically be applied to human material or human subjects, are now available (see, for example, the outstanding review by Marx et al.7). Just as it is possible to present the scientific case that something should be done, it is also possible to consider what should not be done. It is likely that all the speakers in the House of Lords Second Reading debate, and many, but not all, scientists in the pharmaceutical industry, would consider that dogs are essential for the safety testing of new drugs intended for human use. This has worried me for at least 35 years, and FRAME has made many attempts to make some progress. However, it has not been possible to conduct a proper scientific analysis, since this use of dogs was overwhelmingly conducted by or for the pharmaceutical companies and the results of their studies are only rarely made publicly available. That problem was partly overcome, when FRAME-funded access was gained to independently collected and evaluated human and dog data for an extensive and varied set of 2,366 drugs. The results of the first stage of my collaborative study with Jarrod Bailey and Michelle Thew, of the BUAV, are presented in this issue of
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ATLA,8 where we reach the conclusion that the preclinical testing in dogs of drugs intended for human use cannot currently be justified on scientific or ethical grounds. We hope that our study will be taken seriously by pharmacologists and toxicologists, by the pharmaceutical industry and the regulatory authorities, and by governments, who will apply our approach to their own data or explain what other approaches they consider to be equally, or more, relevant and reliable. Professor Michael Balls c/o FRAME Russell & Burch House 96–98 North Sherwood Street Nottingham NG1 4EE UK E-mail:
[email protected]
References 1 Anon.
(2011). Animals: Experimentation. Question for Short Debate. Lords Hansard Text for 24 October 2011, columns 618–633. London, UK: Parliament UK. Available at: http://www.publications.parliament.uk/pa/ ld201011/ldhansrd/text/111024-0002.htm (Accessed 28. 10.13). 2 Balls, M. (2011). Animal experimentation and the labelling of drugs. ATLA 39, 497–500. 3 Anon. (2013). Medicinal Labelling Bill [HL]. London, UK: Parliament UK. Available at: http://www. publications. parliament.uk/pa/bills/lbill/2013-2014/ 0011/14011.pdf (Accessed 28.10.13). 4 Anon. (2013). Medicinal Labelling Bill [HL]. Second Reading. Lords Hansard Text for 25 October 2013, columns 1296–1310. London, UK: Parliament UK. Available at: http://www.publications.parliament.uk/pa /ld201314/ldhansrd/index/131025.html (Accessed 28. 10.13). 5 Balls, M. (1991). Comments on labelling related to the animal testing of cosmetic ingredients and products manufactured and/or marketed within the European Economic Community. ATLA 19, 237–244. 6 Anon. (2013). This House would not ban all forms of animal research. London, UK: Understanding Animal Research. Available at: http://www.understanding animalresearch.org.uk/news/2013/10/this-housewould-not-ban-all-forms-of-animal-research/ (Accessed 28.10.13). 7 Marx, U., Walles, H., Hoffmann, S., Lindner, G., Horland, R., Sonntag, F., Klotzbach, U., Sakharov, D., Tonevitsky, A. & Lauster, R. (2012). ‘Human-on-a-chip’ developments: A translational cutting-edge alternative to systemic safety assessment and efficiency evaluation of substances in laboratory animals and man? ATLA 40, 235–257. 8 Bailey, J., Thew, M. & Balls, M. (2013). An analysis of the use of dogs in predicting human toxicology and drug safety. ATLA 41, 335–350.
