EMEA under the microscope

The EU Medicines Agency's role is evolving to meet the needs of new legislation and changing sector trends. Executive director Thomas Lonngren reviews the changes and outlines plans for the future

The European Medicines Agency (EMEA) stands ready to help pharmaceutical companies in the development and marketing of new drugs in an effort to halt and reverse the decline in the number of new medicines being brought to the world market. Similarly, the agency is preparing to undertake conditional approval of new drugs based on positive benefit/risk assessments even where the clinical data is incomplete.

An interview with the EMEA executive director Thomas Lonngren left Manufacturing Chemist with the firm impression that EMEA is preparing to play a much wider and more active role in the development and authorisation of new medicines in the EU, partly arising from the implementation of new EU legislation in the drugs sector and partly from developments in the pharmaceutical industry.

Speaking at EMEA headquarters in London's Docklands, Lonngren said that "for some years now we have seen a decline in the number of new medicines that the pharmaceutical industry is putting on the world market - last year there were only 30 new candidates." This was a complex issue and there were numerous reasons for the trend. "We are not entirely responsible, as regulators, for that, but we are looking into ways to see how we could help the industry and the research society out there," he said.

development bottleneck

In this context the initiation of the European Technology Platform - Innovative Medicines Initiative by the research directorate-general of the European Commission in Brussels was "a very interesting development," he said. This is a special project that will be using money from the EU's oncoming 7th framework programme on research to finance studies into bottlenecks in drug development. The Commission's DG research was making preparations for the 7th Framework Programme "and we're working with them on the Technology Platform - Innovative Medicines Initiative. This is to identify, ahead of time, some of the bottlenecks in research and so help towards better targets," Lonngren said. "We've had problems here because it is taking so long to get a new drug onto the market. Many candidates are failing because of the need to develop the methodology of drug development," he added.

"Now we have identified the bottlenecks but we need to look more into new methodology and better statistical methods. Hopefully there will be hundreds of millions of Euros available for research in this area. There is a major problem with the number of new medicines coming out. We are looking to see what we can do to help get more new medicines on the market successfully, and that is one of our priorities. We're heavily engaged in stimulating drug development," said Lonngren.

conditional authorisation

The introduction of conditional marketing authorisation was signalled when Brussels brought out new legislation in 2001. The idea was to grant a one-year authorisation "provided that there is an important expected health benefit for the patients concerned and that the company undertakes to perform additional monitoring and clinical studies. The practice has been accepted in the US for some years and there has been a feeling in some quarters that European consumers, by contrast, were being denied access to potentially life-saving drugs," Lonngren conceded.

It then became possible to get conditional approval for a drug "if there is a high public need for this medicine on the market and where this medicine is [offering] an added scientific value compared with other therapies on the market". This was a new mechanism provided for in the new legislation "and it could help to stimulate innovation, of course". Linked to this was an increase in EMEA's capacity to give scientific advice in general to the pharmaceutical industry in order to help it with drug development.

These are striking examples of how EMEA has evolved over its relatively short 11-year history. "We have expanded both when it comes to the number of applications coming to the EMEA and also when it comes to the legal responsibility of the agency," Lonngren said. "Most of the new medicines that are now coming onto the European market will probably use the centralised procedure and will come to the EMEA for assessment. It's been a remarkable development, starting with just a couple of people, and now we have staff approaching 400, covering a network of 43 national competent authorities working together."

For the future there are two challenges, both offering new growth opportunities: "First, we have a new proposal from the Commission to introduce new legislation on paediatric medicine which is coming out next year. And then the Commission is working on legislation for advanced medicine and products, including tissue engineering, so we shall have new legal responsibilities and we will, of course, expand," he said.

According to Lonngren, parallel import is a political instrument used in the EU in order to complete the single market. "Parallel import is an acceptable trade in the EU. Our involvement is that we deal with parallel distribution. Other people will judge this matter from the political point of view but we don't have any health-related problem with parallel distribution," he said.

The EMEA head said the agency had begun a programme to increase the flow of information to consumers and health professionals while acknowledging that direct advertising to consumers of pharmaceuticals was forbidden in Europe. The new EU pharmaceuticals legislation called for a better flow of easily understood information to consumers, and the agency had formed a new department to deal with this. "When it comes to healthcare professionals we are now working on a strategy on how we will approach [this sector] later on this year. But direct consumer advertising is a political issue and it's up to the Commission, the Council of Ministers and the European Parliament to decide where we are going with this," he said.

flu vaccines

On the subject of the possibility of a flu pandemic in Europe, Lonngren stressed EMEA had a strategy in place to cope with this. The EMEA role here was "mainly in the area of receiving applications for pandemic influenza vaccines and of course doing the scientific assessments and taking decisions as early as possible in order for the Commission to grant an authorisation at European level," he said. "We have at the moment, on the human side, two applications and we expect to get another two this year. The first positive opinion could in theory come in April/May for an approved vaccine for an influenza pandemic for humans. We are also working with the veterinary industry to produce a vaccine for animals," he said.

Asked how the development and licensing of vaccines could be speeded up and wastage reduced, Lonngren said: "On the human side we have a concept called a core dossier to build up a specific mock-up vaccine that doesn't include the actual strain from the beginning, using a similar strain in order to make clinical tests and so on. Then when we have made an approval and when the strain has been identified by the WHO, it could be a very simple procedure to change the strain in the vaccine, a simple variation procedure. We could easily re-authorise quickly." An internal crisis management plan has also been set up to deal with all the regulatory procedures in a situation created by a new pandemic.

"We also have to follow up the safety of these vaccines on the market," he said. It was extremely important to issue guidelines covering anti-viral treatment and the precise use of drugs, in the case of a pandemic, he stressed. This was an example of speeded-up procedure and there was also a fast track procedure. But assurance of supplies was not EMEA's responsibility, he insisted. "What we can do, of course, is to make sure we have a scientific assessment and authorisation at a European level. It's entirely up to the pharmaceutical companies to deal with the issue of production."

On pharmacovigilance, Lonngren noted that in 2001 EMEA had introduced a "risk management strategy" to improve pharmacovigilance at a European level. "That's been further developed. Today we're talking about the European Risk Management Strategy which also involves all the EU national agencies and which includes action on four specific areas."

These were:

Improved risk identification in order to complete the European database and find other ways to detect safety signals. "We've tried to organise a European network of epidemic centres to co-ordinate other kinds of data about the side-effects of medicines," he said.

Improved risk evaluation in order to improve methodology and benefit risk assessment.

In risk minimisation "one very important initiative is that companies now have to submit, with their application, a risk management plan that will include action on risk minimisation when they're putting the product on the market."

On risk communication "we are working with member states to increase the information available about side-effects and we are now building a web-site to make this information available."

Turning to herbal medicines, Lonngren focused on how EMEA had a new committee created mainly to develop lists of herbals that could be accepted on the local markets "and to produce monographs." There was a mechanism in each EU member state to set up special registration systems for so-called medicines for traditional use. "The EMEA committee supported member states in efforts to promote the safety of herbals and then monographed and listed them so that it was then "easier for member states to grant authorisation".

future financing

Lonngren said 70% of EMEA's finances came from application fees with the rest coming from the EU budget. He noted recommendations in the European Parliament that EMEA's work in pharmacolovigilance and safety in medicine should not be financed from fee income. This had been talked of for years, he said. "The Parliament is very supportive of our activities and tries to help us with our financing. We're quite happy with the present division of our income and it has worked quite well over the life of the agency. But of course I don't know what will happen in the future financial perspective of the EU," he said.

When asked about the introduction of new medicines and technologies like gene therapy, stem cell therapy, nanomedicine and tissue engineering, Lonngren said this was only partly covered by existing legislation. The Commission had therefore begun action to bring in special legislation for such products and this was at present up for public consultation.

"We've been working in these areas for many years now and we have a special task force to coordinate all the activity. We've had several special ad hoc working parties of expert groups to deal with gene therapy and tissue engineering. There are a lot of initiatives to develop new technologies, new medicines in this area. There is a need for clarity about the issues here and for industry to demonstrate efficacy and safety. We are trying to understand where we may need to increase our competence and where we may have to give guidelines to the industry. Much of this is at an early stage of development, both in the US and Europe, and we are working together with the Americans," Lonngren said.