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Indecision and incoherence in Brussels is leading to major concerns regarding the development of medicines in the EU. Political conflicts and lack of co-ordination on topics such as cancer research, stem cells and genetically modified animals have added to the air of uncertainty concerning the future conditions for the European pharmaceutical industry. And while European politicians, officials and researchers continue to squabble, people in developing countries requiring urgent access to drugs continue to go without essential treatment.
Try as it might, the European Union (EU) just never seems to be able to get it quite right when dealing with drugs. Whether at home or abroad, things just don't fall into place the way that EU leaders want when medicines get discussed; and the last few weeks have seen much evidence of what weathermen like to call "more of the same" affecting the European world of pharmaceuticals.
At home, Brussels' plans for reforming the regulatory framework for pharmaceuticals become more complicated by the week.1 Now, the European Parliament is looking for approximately 700 changes in the way the EU is hoping to refine its systems for drug authorization, review and inspection - and since many of the proposed changes head in opposite directions, it's going to be impossible to find early agreement on that (of which, doubtless, more anon).
Even in more limited areas, however, where the EU thought it had got it more or less right, it is displaying its consistent ability to snatch defeat from the jaws of victory. For instance, after a decade of anguished reflection on how to regulate clinical trials, it won broad consensus for a new directive last year. It wasn't perfect, because of numerous conflicting starting points by the many players involved - investigators, sponsors, regulators and, of course, patients - but it seemed to hold out some prospect of a more harmonized and predictable EU environment for clinical trials.
Now, however, as the EU moves on to the final stages of implementation of this new rule, it is spreading alarm, despondency and disaffection among nearly all interested parties; the detailed guidelines it has come up with on how the new rule should work re-introduce almost all the national divergences and contradictions in clinical trials regulation that the initiative was meant to remove. Even the chairman of the Committee for Proprietary Medicinal Products at the European Agency for the Evaluation of Medicinal Products, Daniel Brasseur, has joined the chorus of concerns being expressed at the prospect of further constraints on European clinical trials and, ultimately, on European pharmaceutical industry employment.
Meanwhile, the EU has admitted that the considerable investments made in cancer research throughout Europe are not producing the results that health practitioners and citizens would expect. It recognizes that this is partly because of fragmentation and duplication of research efforts within member states and across Europe, and the lack of coherence at European level, despite years of earnest attempts to build better European systems, to promote collaboration. In September, the European Commission (EC) and the European Parliament organized yet another conference on the theme, this time entitled "Towards Greater Coherence in European Cancer Research," with the aim of helping to build a joint European strategy for cancer research. It spoke boldly of "leveraging the opportunities offered" by the EU's latest research framework programme (which earmarks up to E400 million for cancer) to rally all involved parties.
But the mere fact that another conference is being held just highlights how ineffectual EU efforts have been to date in this field. "Cancer research is a priority within the health research field," the Commission says, but it is still at the stage of bringing together "scientists, clinicians, patient groups, policy makers, representatives from national and European public and private cancer organizations, and industry" to find a way ahead. An attempt is being made to look determined and great publicity is devoted to the fact that this new meeting also features such European luminaries as Parliament President, Pat Cox, and Philippe Busquin, Commissioner for Research. But this is not much of an advertisement for what has been done so far.
The new research programme that the EU is placing such faith in is still in trouble. It is destined to start in 2002 and run to 2006, and after almost interminable discussions and disputes during the last 2 years, desperate attempts have recently been made to finalize all the rules needed in the EU to make it function. Pious EU hopes, expressed in July that all would be concluded during the summer break, have proved to be delusionary. This E17.5 billion programme, in which health and pharmaceuticals should qualify for a major slice, has been blocked again by a squabble concerning stem cell research.
Members of the Parliament who support stem cell research accused the EU's 15 member states of "a betrayal" in August, when they heard that what was being planned was an effective embargo on stem cell research. The Parliament's committee on industry and research, which has been a staunch backer of biotechnology innovation during recent years, met on 26 August for the first time after the summer recess, and denounced what they thought was a last-minute deal reached behind closed doors by member states just before the summer break. What has angered parliamentarians is that EU governments backed away from allowing immediate EU funding of stem cell research under the EU's new research framework programme.
Right at the end of July, as Denmark, the country currently holding the EU presidency, tried to put the final touches to the rules for the framework programme, it found itself in trouble with Italy - which had consistently opposed EU support for stem cell research and was consequently refusing to sign up to the programme as a whole. So, the presidency put together a compromise text for this part of the programme's rules, to avoid a confrontation with Italy. The text recommended that the EU Council of Ministers should "establish by 31 December 2003 detailed implementing provisions concerning bio-ethical scrutiny of research activities involving the use of human embryos and human embryonic stem cells" - and as a result implied that EU funding of such activities will be postponed until then.
The chairman of the European Parliament's research and industry committee, Spanish socialist, Carlos Westendorp y Cabeza, said this temporary embargo on EU funding for human embryonic stem cell and human embryo research "has taken hostage one part of the research world - embryonic stem cell research." But now the presidency has stated that no deal has yet been reached. What members of the Parliament took to be a final decision was in fact only a compromise proposal that the presidency floated during the summer break, in the hope of overcoming Italian opposition. But Italy refused to sign up to it, saying it was not prepared to put the decision off to a later date. So the programme remains on hold, and the Danish minister for science, technology and innovation, Helge Sander, has admitted that "a compromise on this sensitive issue has become a precondition for final adoption of the specific programmes." It is now scheduling urgent talks at ministerial level to win the agreement needed for the programme to go ahead.
Another domestic row is brewing regarding the use of genetically modified animals in biomedical research, a subject that attracts the attentions of the numerous European environmentalists, animal rights activists and opponents of research in general. The main European drug industry association, the European Federation of Pharmaceutical Industries and Associations (EFPIA), has launched a defence of the practice in a pre-emptive move to head off a growing wave of concern before research plans are derailed by further hostile legislation. In a new position paper, EFPIA argues that genetic approaches have already become indispensable for a continued deepening of understanding of disease, and that basic research with transgenic animals is therefore necessary.
The industry points out that it recommends the application of best practices for the use of transgenic animals. Such animals must only be used in biomedical research where no other scientifically valid means of obtaining the required information is possible. Only trained and competent staff are allowed to be involved in the use and care of all animals in research.
Regulations controlling the production and use of genetically modified animals must be strictly observed. The most efficient and refined techniques should always be used; the publication of new mutant data and strain characteristics should be encouraged by the pharmaceutical industry to avoid duplication; and models should be distributed to a wider scientific community.
It insists on the storage (such as cryopreservation of embryos or freezing of sperm) of strains when they are no longer needed, with cataloguing and access to other researchers. Careful consideration should also be given to the health status of transgenic strains. Producing new strains to a high health status may remove the need for rederivation at a later date, it says. And in an attempt to placate critics, it says the research-based pharmaceutical industry supports all efforts to reduce the use of animals in medical research. But "animals will remain necessary," as medicines administered to an entire organism can have effects that are not detectable when using cell or tissue cultures, biochemical assays or computer simulations. This autumn will demonstrate how convincing this argument is in averting new controversy.
Abroad, things have not been going well either. The World Summit on Sustainable Development (Johannesburg, South Africa), where the EU sought to showcase its concerns for the third world, provided more of a platform for criticism of western and European medicines and health policy with respect to the developing world. The EC sponsored a conference on science and technology at the summit, to demonstrate that research is a powerful instrument for fostering capacity building in developing countries and strengthening partnerships with Europeans. Health and a new pharmaceutical research scheme known as the European-Developing Countries Clinical Trials Partnership, in particular, was high on the agenda. But despite such initiatives, and accompanying heavy-duty lobbying from the pharmaceutical sector itself to defend the industry's record, the broad perception to emerge from Johannesburg was that the west in general, and the European pharmaceutical sector, was not meeting the evident needs.
It was not only from the predictable critics among non-government organizations that there was loud and negative comment regarding the Johannesburg attainments. Even the International Pharmaceutical Federation (IFP) has now turned its attention to the perceived deficiencies in western attention to medicines provision. At its recent World Congress of Pharmacy and Pharmaceutical Sciences (Nice, France), which overlapped with the Johannesburg summit, it pointed out that one third of the world's population lacks access to essential medicines. It listed the sad litany of problems
And, it went on, research and development into diseases that affect the poor has stagnated because of a lack of economic incentives - the last major new TB drug was developed 30 years ago. Resistance to all infectious disease treatments is on the rise. IFP does not lay the blame uniquely at the door of the pharmaceutical industry or of the authorities in the developed world. Many developing countries have pharmacy regulatory systems staffed with well-trained individuals who are unable to operate because of a lack of resources, corruption or ineffective laws, it concedes. Some countries are unable to stop the flow of counterfeit drugs despite possessing the appropriate technical knowledge and equipment to do so, and others do not have the resources to test the quality of new drugs that come on the market. In many instances, countries do not have the drug management infrastructure and resources to effectively and efficiently procure, process and distribute medicines. Where systems do exist to ensure delivery of medicines, the lack of resources often limits the extent to which patients can afford treatment.
But IFP makes it clear that a definition of the problem of access and its extent is still needed, and that measures have to be developed to address the inadequate availability of medicines in developing countries. It also identifies price and quality as major issues, and the need to increase North–South collaboration and the transfer of knowledge and skills, alongside the need to prescribe, distribute and use medicines appropriately.
Pharmaceutical technology, in Europe and beyond, still has some challenges to meet if it is to win wider appreciation.
1. Albedo, "Drug Plots Thicken in Deepest Brussels," Pharm. Technol. Eur. 14(9), 19–23 (2002).