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Volume 23, Issue 6
The greatest challenge faced by the EMA is the continuing expansion of the EU.
The EMA has extensive obligations in Europe, including issuing scientific opinions in support of EU-wide marketing authorisations, offering advice on medicine-related issues, and working with institutions and partner agencies on major European public-health issues. The agency works closely with the EU's 27 member states, as well as the European Economic Area (EEA) countries of Norway, Iceland and Liechtenstein, and relies on these countries to maintain regulatory standards in Europe on its behalf. Unlike the FDA in the US, the EMA itself does not carry out day-to-day operational matters itself. Representatives of the member states serve as members of the EMA's management board, and the EMA's six scientific committees and network of 4500 scientific experts are also nominated by the member states.
From the pharma industry's point of view, the most high-profile role for the EMA is coordinating the centralised authorisation procedure for medicines, which results in a single marketing authorisation that is valid in all member states and EEA countries. This regulatory procedure is compulsory for biotech medicines, which represent a growing percentage of the drug output of major companies. Applications for the centralised procedure are submitted directly to the EMA where they are evaluated by scientific committees. After this, the committee adopts an opinion on whether the medicine should be marketed or not—a process that can take up to 210 days. The opinion is then sent to the EC, which is the ultimate body for granting marketing authorisations in the EU. This last process is almost a formality; no opinion has ever been overturned by the EC. Once the marketing authorisation has been granted, a company can begin to market the product across the EU.
One of the challenges for the EMA in coordinating the centralised procedure is that the EU has expanded considerably since its inception in 1995 (see Table I). Therefore, the EMA has had to bear in mind that its decisions have a wider impact on an ever-increasing population of patients. Creating a robust regulatory system for the EU was never considered a straightforward task, but the EMA has faced the additional challenge of a growing number of regulatory partners to interact with and oversee. As its remit widens to taken on new European countries, the agency must also rely on regulatory bodies in entrant countries for operational matters. While there is an expectation that these bodies will work to the same standards as more long-standing members, they will inevitably lack the same level of experience.
Table I: EU expansion.
The EU has always been characterised by expansion and the political drive to pursue this strategy continues to have a knock-on effect on the EMA's workload. However, the EMA has become adept at planning in advance for future expansion, particularly since May 2004 when the EU expanded to take in 10 new countries with a combined population of almost 75 million (1,2). It was around this time that the agency's founding legislation was also changed to reflect its expanding role with Regulation (EC) No 726/2004 replacing Regulation (EEC) No 2309/93 (3).
After the signing of their respective accession treaties, the national authorities of the candidate countries were invited to send observers to the EMA's scientific committees and working parties, with effect from April 2003 (4). As well as ensuring that the national agencies of entrant countries became familiarised with EMA processes and standards, preparations also had to be made for the translation of EMA documents into new languages. During 2003, the agency's website was updated with an estimated 10000 new documents (4). The EMA was also tasked with ensuring that the new regulatory authorities were linked to EudraNet (the European Telecommunication Network in Pharmaceuticals), an IT platform that enables scientific experts, policy makers and other designated staff to have a secure electronic environment to exchange and share information on a pan-European basis (5). There was also a need to recruit and train new staff; some of this training was achieved through the secondment of national experts from accession countries. At this point in time, Bulgaria and Romania were not part of the EU, but due to the short timeframe for them to join, the EMA also started cooperating with their national agencies.
In late 2009, the EMA launched its Instrument for the Pre-accession Assistance (IPA) programme, for EU candidate countries in pre-accession activities (3), which included Croatia, the former Yugoslav Republic of Macedonia, Turkey, Albania, Bosnia and Herzegovina, Kosovo, Montenegro and Serbia. An earlier initiative, backed by €600000 from the EC, had focused on supporting the participation of the former Yugoslav Republic of Macedonia, Croatia and Turkey in EMA activities.
To fund the latest IPA programme, from 2009 to 2011, a budget of €900000 was requested from the EC (3). In a similar fashion to the approach the EMA adopted for the EU's expansion in 2004, nominated representatives of the candidate countries were invited to selected meetings and training courses as observers. As well as scientific training, a number of legal measures were also conducted so that EU technical regulations could be transposed into the national legislation of the participating candidate and potential candidate countries. According to the EMA, the programme is not only for the national agencies to gain experience of the current system, but also for them to feel that they are equal, mutually respected partners. As part of this, the EMA sends members of its staff to the countries to talk to the national agencies about their respective needs.
The scope of the project was expected to vary according to the needs of the country concerned and the stage of its candidacy (6). The EMA has adopted a three-step approach to training, moving from general topics through to more specific ones. Initially, information regarding the pan-European approach to regulations is provided to national representatives at the EMA headquarters in London (UK). The next step is a series of conferences held within candidate and potential candidate countries, which involves representatives from the pharma industry, as well as other interested parties. This allows the national agencies not only to develop a solid understanding of the EMA's work and processes, but also to understand which stakeholders are involved and how to interact with them. The third training step involves participation from national experts in specific training sessions organised in London.
The EMA is confident in its system and believes that the step-wise training will ensure the implementation and enforcement of harmonised regulatory and technical requirements. It also aims to make sure that any divergent practices still existing within candidate and potential candidate countries are eradicated in time for their entry into the EU. Progress of the overall IPA project is to be monitored by the EMA's Administrative Unit, with checks to ensure that goals are being achieved and that sufficient time is allocated to carry out remaining activities. Annual reports will be posted on the EMA website (6).
Of all the countries involved in the IPA process, Croatia is working particularly closely with the EMA, since it is due to enter the EU on 1 June 2012. Indeed, so far, the only detailed reports available on the EMA website relating to candidate countries are for Croatia. The work with Croatia was kick-started in November 2008, when a conference involving more than 350 participants was held in Rijeka (7). The meeting was timed to coincide with the fifth anniversary of the Croatian Agency for Medicinal Products and Medical Devices (ALMP), and featured presentations from experts at the EC, the EMA, the ALMP and the National Medicines Agency of Romania. The involvement of Romania's regulatory agency was considered particularly important because as a recent EU entrant, it was able to offer its Croatian counterparts a unique perspective on the post-accession experience.
In January 2011, the EMA and the ALMP began a pre-accession linguistic checking process for product information in the Croatian language (3). Guidance documents, available on the EMA website, have been prepared to explain how marketing-authorisation holders should translate their product information into Croatian and submit it for checking. There are also product information templates translated into Croatian, and reference documents for the Croatian translations of European country names and non-standard terms used in product information. A phasing-in process for EC decisions on centrally authorised medicines will take place to coincide with Croatia's entry date, which will avoid any delays in the supply of medicines to Croatia, as well as prevent any non-compliant products with Croatian translations gaining access to the markets of other EU member states.
Prior to the 2004 expansion of the EU, some observers had expressed concern at the inclusion of Central and Eastern European countries and how they might affect pharmaceutical regulation. A primary concern was that these new countries had never had a chance to influence the development of EU regulations in line with their capabilities (8). Some countries were also believed to lack the institutional structures to meet new regulatory standards, and the means to sufficiently implement and enforce European regulations (8). It would appear that these views were rather pessimistic. Despite the fact that newer entrant countries have had limited regulatory experience for pan-European matters, the EMA is already preparing for a new wave of expansion.
1. Europa, "The 2004 enlargement: the challenge of a 25-member EU", Europa website 2007. http://europa.eu (accessed 12 May 2011)
2. I. Eckhart, "The European Medicines Agency (EMEA) — from Research to Therapies", Bridges 11 2006. www.ostina.org (accessed 12 May 2011)
3. EMA, "European Union enlargement. EMA", EMA website 2011. www.ema.europa.eu (accessed 12 May 2011)
4. Anon., "EMEA in the European system", Bull. Soc. Sci. Med. 1/2004, 87–92 (2004).
5. IDABC, "EUDRANET: European Telecommunication Network in Pharmaceuticals (EMEA)", Europa website 2004. http://ec.europa.eu (accessed 12 May 2011)
6. EMA, "EU Regulatory Network - Challenges and Opportunities for Croatia", EMA website 2008. www.emea.europa.eu/htms/euenlargement (accessed 12 May 2011)
7. EMA, "Successful Rijeka conference strengthens EU-Croatian cooperation on medicines regulation", EMA website 2008. www.ema.europa.eu (accessed 12 May 2011)
8. H. Prange, Queen's Papers on Europeanisation No 8/2002 (2002). www.qub.ac.uk92 (accessed 12 May 2011).