Agency Reorganizes for European Future

The European medicines agency caught out this columnist at the end of last year. Just days after the December issue went to press, including the directory of European regulatory authorities, the agency announced a new organizational structure.

Peter O'Donnell

Among the highlights of the new structure, all human pre- and post-authorization activities have been integrated into one unit. The aim is to guarantee a more coherent management of medicines right throughout their lifecycle.

A new unit has been created for patient health protection, strengthening the agency's focus on safety-monitoring of medicines. In addition, all the agency's management processes for product data and documentation are to be made more efficient through setting up a group dedicated to keeping this seamless too.

The reorganization, only the second since the agency was created in 1995, is a response to the growth in the agency's responsibilities and tasks. The number of medicines it oversees has increased, its procedures have become more complex, and the number of its scientific committees and advisory groups has rocketed—all bringing the need for enhanced coordination and support.

The workload is likely to increase: the legislative proposals currently being considered by the European Parliament and Council—on toughening up pharmacovigilance, providing more product information to the public, and combating counterfeiting—will each add to the agency's responsibilities.

At the same time, the agency has decided to, at last, rectify an absurdity in its public profile that this columnist has long been a critic of. It has bowed to the imperative of common sense, and has discarded its pompous legal title (European Medicines Evaluation Agency) in favor of the working title it has always been known by—the European Medicines Agency. It has modified its Web and email addresses accordingly, to www.ema.europa.eu, and has replaced the "EMEA" logo with a graphic of a pill.

It is also upgrading its Web site, which receives 700,000 visits each month, with the needs of the public in mind, and providing better access to information on public-health issues. The agency says it hopes its new visual identity "will help to improve the quality and consistency of our communications with our partners and the public." The public angle is becoming a leitmotif of the agency: "Communication with the public is an important aspect of the agency's work, so it is equally important that we have professional communications materials to work with. A second objective for developing the new visual identity was to ensure that the agency's materials communicate to the public a clearer message about its role and activities," the agency said as it announced the new look.

The new responsibilities

Under executive director Thomas Lönngren (who is himself due to leave in mid-2010), Patrick Le Courtois is now head of human medicines development and evaluation. This unit is responsible for all activities relating to medicines for human use, from the development stage right through the scientific advice and product life-cycle, including special requirements for pediatric, orphan, and advanced therapy medicinal products. It provides the secretariats of many of the committees, working parties, and scientific advisory groups for human medicines, and provides support for emerging science questions. It also includes the agency's office for smaller companies.

Noël Wathion is head of patient health protection, which is now responsible for "a proactive approach" to pharmacovigilance and risk management throughout the lifecycle of centrally authorized medicinal products for human use. It manages EU procedures aimed at reviewing the benefit and risk of centrally and nationally approved medicines, and is responsible for crisis management of centrally authorized products.

It is this unit that provides regulatory and procedural support to staff, scientific committees, working parties, and experts involved in medicines for human use, and that provides the secretariats for the principal scientific committees. It conducts the quality review of product information for patients and health care professionals, and organizes relations with patient groups and other outside stakeholders.

Wathion's unit is of particular interest to readers of Applied Clinical Trials because it coordinates verification of compliance with good clinical (and manufacturing and laboratory) practices, and pharmacovigilance requirements. It is responsible for the implementation and operation of the clinical trials framework in the EU. It also manages suspected quality defects and counterfeit medicines and coordinates the sampling and testing of centrally authorized products, as well as operating the schemes for certificates of medicinal products and parallel distribution notifications.

Under Wathion, Fergus Sweeney remains in charge of compliance and inspection, and Ana Rodriguez Sanchez Beato is responsible for clinical and non-clinical compliance.

Responsibilities in action

Meanwhile, the agency has had meatier matters to deal with than the design of a new logo. Over recent weeks and months it has inevitably found itself at the center of the European response to the H1N1 threat. As of the beginning of December, the agency started to publish weekly pandemic pharmacovigilance updates, to provide information on adverse reactions reported after the use of centrally authorized pandemic influenza vaccines and antivirals in the European Union. The updates also flesh out the information the agency regularly published during the year on the development and approval of medicines for use during the pandemic.

The information is intended to support EU institutions and the 27 member states in what they tell doctors and the public, and to provide additional input to recommendations on the use of vaccines and antiviral treatments.

The information on adverse reactions in the update comes from EudraVigilance, the central database on adverse reactions that the agency manages, and is based on reports from member states and marketing authorization holders. The weekly update also provides an estimate of how many doses of pandemic vaccines and antivirals have been administered in the European Union, and other information that helps put adverse reaction reports in context.

So far there are three pandemic vaccines—Celvapan, Focetria, and Pandemrix—on the market, all authorized by the European Commission in the autumn.

The agency's specific responsibilities in relation to the pandemic include reviewing data submitted in support of marketing authorization applications for vaccines or treatments, monitoring their safety, and recommending changes to their use or authorization, where necessary. It does this in close liaison with EU member states, the European Commission, the European Centre for Disease Prevention and Control, and the World Health Organization.

Monitoring strategy

The agency has drawn up a European strategy for benefit–risk monitoring of H1N1 vaccines, which recognizes that only limited data on safety and immunogenicity will be available when member states start using them. The continuous mutation of the influenza virus also means that the effectiveness of vaccines needs constant measurement.

"Active post-authorization monitoring of the vaccines will be needed to detect and assess adverse events following immunization and, for each vaccine, the frequency and severity of these will need to be balanced with the available information on their effectiveness," says the agency. It has set out a strategy for European collaboration to deal with the challenge of different vaccines, doses and adjuvants being used in different member states, giving rise to distinct safety and effectiveness profiles.

As mass vaccination takes place, data generated by public health centers on safety and effectiveness become important for reinforcing the identification and evaluation of any new issue that may arise, so the strategy proposes interactions between health professionals, national authorities, and the agency, to strengthen the monitoring process.

But the main responsibility for monitoring safety and effectiveness of vaccines remains with vaccine manufacturers, the agency insists. Specific duties in addition to routine regulatory obligations have been defined by the agency's committee of human medicinal products, including a prospective safety cohort study for each vaccine, surveillance of adverse events of special interest, monitoring of special population groups (pregnant women, children and immune-compromised), and studies on effectiveness and immunogenicity.

Peter O'Donnell is a freelance journalist who specializes in European health affairs and is based in Brussels, Belgium.