The stamp of approval

NGP talks to Executive Director Thomas Lönngren about implementing these changes and the Agency’s role in drug authorisation. Interview by Rob Plastow.

The European Medicines Agency (EMEA) is Europe’s central drugs assessment agency, working in a similar manner to – and often alongside – the US Food and Drug Administration. The EMEA has recently been looked to for the first signs of the development of a bird-flu vaccine, and the speed and efficiency at which it could assess such an application would determine how fast such a vaccine would become available in Europe.

NGP. What affect do you believe the provision of the EMEA has had on the health of EU citizens?
TL. It is the Agency’s mission to protect and promote public health. We fulfil our mission in several ways:

The European Medicines Agency contributes to the availability of good medicinal products in Europe by stimulating the development of innovative new medicines, by assisting pharmaceutical companies with approval procedures, by evaluating the safety, efficacy and quality of new medicines prior to authorisation and by constantly monitoring them once they are on the market.

Patients in all EU Member States have better access to new and important medicines because, by granting one single marketing authorisation through the centralised procedure, such new and important medicines are available to all patients in the European Union. Similarly, essential information about these medicines for doctors and patients is available in all EU languages.

From the start, the creation of the Agency built on existing national expertise, and by bringing that expertise together, we want to provide Europeans with an even better system of medicines regulation. Patients in all Member States benefit from the knowledge and expertise of the best experts, wherever in Europe they may be.

NGP. How will the Commission’s proposal for new EU-wide rules to facilitate gene, cell and tissue-based therapies affect the EMEA?
TL. This will have quite a big impact on the EMEA. At this stage, however, there is not much for us to say. The European Commission has published the proposal including background material, which provides useful information

NGP. What does the new EU pharmaceutical legislation mean to the operation of the EMEA?
TL. We welcome the full entry into force of Regulation (EC) No. 726/2004, which heralds a more robust, modern, effective and competitive regulatory framework for pharmaceuticals in Europe.

Title IV, which entered into force on 20 May 2004, gave the EMEA important new responsibilities and enabled it to undertake necessary administrative and structural reforms. The remaining titles came into force on 20 November 2005. They provide us, and our partners in the European regulatory network, with significantly greater powers and better tools for the authorisation and supervision of human and veterinary medicinal products.

Implementing the new legislation will result in major benefits for Europe’s patients, animal population, healthcare professionals, pharmaceutical companies and regulatory authorities alike, with the most significant benefits in the following priority areas:

• Faster access to innovative new medicines
• Improved safety of medicines in the marketplace
• More openness and transparency of regulatory procedures
• Enhanced communication and provision of information,
• Increased competitiveness of Europe’s pharmaceutical industry

NGP. What changes have been made to speed up and streamline EMEA’s provision of scientific advice to sponsors?
TL. The EMEA has provided scientific advice to sponsors since 1996. The introduction of the new EU pharmaceutical legislation gives us a greater mandate to provide scientific advice (SA), particularly regarding the development of new therapies, with direct responsibility for the Executive Director to establish efficient structures for the provision of scientific advice.

The Agency’s Committee for Medicinal Products for Human Use (CHMP) adopted a new procedure in April 2005. One of the key aspects of this procedure provides for earlier and greater involvement of internal assessors and external experts from the SA pre-submission phase to final SA. Based on this involvement starting from the pre-submission phase, it will be possible to streamline the procedure to allow finalisation within 40 or maximally 70 days (compared to 100 days under the framework of the old procedure). This new framework will also consolidate the involvement of CHMP by formalising a peer review before final adoption of the letter to maximise the clarity and ensure consistency in the provision of scientific advice.

Another key aspect includes more interaction, communication and transparency with stakeholders, through extension of the scope and increased use of follow-up procedures, publication of standard Q&A documents for frequently asked questions, and organisation of workshops and think-tank meetings on specific and rapidly evolving topics.

The new SA framework also envisages more collaboration with academia, learned societies and patients’ organisations. Moreover, new measures such as incentives to Small- and Medium-sized Enterprises (SMEs), additional specific expertise and new competences will be put in place to take into account the extended scope of SA as defined by the new Regulation.

In the context of cooperation with other non-European authorities, EMEA and FDA have a programme for companies to obtain parallel scientific advice from the two agencies. The programme includes a mechanism for the EMEA, FDA and companies to exchange views on scientific issues during the development phase of new medicinal products. The parallel advice programme focuses in particular on important breakthrough drugs.

NGP. What affect will this have on the industry and the sick?
TL. The provision of scientific advice to sponsors (whether pharmaceutical industry or other researchers) is one of the main priorities for the EMEA. It is a key part of our response to the EU strategy for improving the competitiveness of European-based research and development of medicines.

Because better scientific advice means better, more effective and faster development of safe and effective medicines, it is ultimately beneficial to patients and healthcare professionals as well.

NGP. The EMEA recently announced that it could approve an effective vaccine against bird flu in a matter of days. How would you do this and have you had any first draft applications from manufacturers yet?
TL. We have developed the concept of ‘core dossiers’ to facilitate the submission and review of applications for pandemic influenza vaccines. This concept allows the CHMP to review the bulk of an application prior to the actual outbreak of a pandemic.

In the core pandemic dossier, the applicant should justify the development strategy, validate production processes and analytical methods, and report the findings from pre-clinical tests and clinical trials. To achieve this a ‘mock-up’ vaccine should be produced, ideally in the same way as the intended pandemic vaccine.

Once the WHO has identified the pandemic strain, companies would submit a pandemic variation application, which contains only data that is new and relevant for the pandemic strain. The CHMP could approve a variation to the core dossier, following a ‘rolling review’, within a few days.

So far, no core dossier applications have been submitted. The Agency has, however, put in place all necessary procedures to speed up any applications. In this context the CHMP made a commitment recently to accelerate the scientific evaluation of applications for scientific advice and marketing authorisation for pandemic influenza vaccines ‘core dossiers’, thus increasing pandemic influenza preparedness and helping to ensure that such vaccines are available to EU citizens as soon as possible in the event of an outbreak.

In addition, the Agency also constantly reviews antivirals. Influenza antiviral medicinal products and pandemic influenza vaccines have a complementary role in the management of an influenza pandemic, because in contrast to pandemic vaccines, influenza antivirals can be used from the very early phase of the influenza pandemic. The Agency, after compiling and reviewing scientific information on antiviral medicinal products, has recently published a review on influenza antiviral medicinal products for potential use during pandemic.

Who are the EMEA?

Safe, effective and high-quality medicinal products play an important role in the protection of public and animal health in our society. Without them, the efforts of healthcare professionals working on the prevention and treatment of illness and disease would be severely undermined.

According to the legislation establishing the EMEA, the Agency is responsible for coordinating the existing scientific resources put at its disposal by Member States for the evaluation, supervision and pharmacovigilance of medicinal products.

That responsibility places us at the heart of the European regulatory system for human and veterinary medicinal products – a system that has evolved over a period of forty years and whose objective is to harmonise procedures in the pharmaceutical sector for the benefit of Europe’s citizens.

Within the European system, the EMEA operates the central procedure for the marketing authorisation of medicinal products. Companies submit one application to the EMEA. Our scientific committee carries out one evaluation and – if the medicinal product under evaluation is safe, efficacious and of high quality – adopts a positive opinion, which is sent to the European Commission to be transformed into one marketing authorisation valid in 25 EU Member States and the EEA-EFTA states: Iceland, Liechtenstein and Norway.

We also assist pharmaceutical companies that wish to develop a new human or veterinary medicinal product by providing guidelines or giving scientific advice. Pharmaceutical guidelines provide essential information to be taken into account in the research and development of new medicines. Based on the most up-to-date scientific knowledge they are a key part of the Agency’s work within the European Union pharmaceutical regulatory system. Many of the guidelines are the result of the European Union’s harmonisation activities with Japan, US and other international partners through the international conferences on harmonisation for human and veterinary medicines (ICH and VICH). We constantly review and update these guidelines in order to reflect the latest scientific knowledge at any given time.

Scientific advice is given on specific questions of individual sponsors relating to the manufacturing of a product, the pre-clinical safety and clinical development and the conduct of various tests and trials necessary to demonstrate the quality, safety and efficacy of medicinal products to industry.

Scientific advice is normally requested during the initial development of the medicinal product (before the submission of an application for marketing authorisation), but it can also be requested in the post-authorisation phase, addressing issues such as post-marketing studies in the context of the future development of a medicinal product.

Thanks to the services the Agency provides in the development phase, pharmaceutical companies can proceed to the evaluation phase with greater confidence of obtaining marketing authorisation.