The European Medicines Agency (EMA) is a unique institution, pursuing a mandate shared with a complex web of national and regional groups, each able to place a distinctive imprint around the delicate task of certifying the safety and efficacy of new drugs. In return, EMA has made a virtue of necessity. It filled the regulatory space opened by the relentless progress of science and new information technologies to gradually expand its remit in a way that has maintained consensus among stakeholders.
In fact, EMA has escaped the toxic politics that the US FDA is now mired in by securing a reputation for such predictability that it attracts scant attention from headline-seeking media and the political classes, even as the issues that surround drug approvals become more prominent and controversial.
Yes, there is bureaucratic merit to being boring, as reflected in EMA’s record of having achieved its prime commitment to meet legislated review deadlines for new drug applications in every one of its 15 years of operation. Much of the credit is attributed to the Agency’s outgoing Executive Director, Thomas Lönngren of Sweden, whose five-year term — his second and final, as required by statute — expires on 31 December. An advantage for Lönngren has been that, unlike the FDA, the Agency is autonomous.
It does not report directly to the EU Commission or the European Parliament but to a Management Board composed of a cross-section of institutions ranging from the member states to the EU agencies and even patient representatives. In that regard, the European process remains in many ways an insider game — you know which stakeholders count and how to target them. With Lönngren now poised to move on — to a post advising governments, professionals, and the industry on the drug regulatory process — Pharm Exec sat down with him in London last month to review his record, sift through the next wave of regulation, and highlight what’s not [vital] on the industry’s own reform agenda — but should be.
William Looney: Your decade as Executive Director might best be characterized as an era of institution building. Has what you’ve achieved helped preserve Europe’s position as the world’s largest market for medicines?
Thomas Lönngren: The Agency is a relative newcomer to medicines regulation, having begun operations only in January 1995 — some seven decades after the creation of FDA in 1930. So we have had a short learning curve. We are also an institution unique to Europe, with a mandate to coordinate scientific assets from the 27 EU member states and three European Economic Areas (EEA) countries for the evaluation, supervision, and pharmacovigilance of medicinal products for human and veterinary use.
What this means in practice is that we are an institution built around partnership, with our principal contacts being the national registration authorities with whom we administer a single, centralized EU-wide marketing authorization for new medicines granted through the European Commission.
This task is a delicate one, as we must balance the need for process coordination with a complex web of policy interactions. Partnering well requires political wisdom; the metric for success is being accountable to the European institutions and the member states through good science, strong evidence, independent professional judgment, and — most importantly — a high level of transparency and communication. The “incentive to consult” avoids the hubris that sometimes accompanies the exercise of power in the public trust. It gives us a rich portfolio of expertise to draw on.
We are constantly exposed to different perspectives and are expected to explain and justify our actions to the same competent authorities in each of the member states, which is a guard against complacency and the bureaucratic mindset. This is one of the benefits of our approach, as it fosters a capacity for continuous innovation in the way we regulate. We have to be networked — it’s wired into our DNA. The fact that national authorities still have a role in issuing a marketing licence makes us nimble and doubly aware of how we impact public health.
This was also a period of significant expansion where the Agency was expected to take on new responsibilities. Which of these were most important in defining what the Agency is today?
When I became Executive Director in January 2001, we had about 150 employees; today we are at more than 850. The Agency administers a network of more than 5,400 experts distributed among 44 drug-licensing authorities in 30 countries. We manage six scientific committees responsible for our centralized authorization procedure, which is now mandatory
for all new technologies, including biologics, with a seventh committee — on pharmacovigilance — in preparation. On top of that there are 35 expert working parties that supervise the development of clinical guidelines and support the preparation of dossiers. What happened here was the political leadership in Brussels recognized that completion of the internal market required a stronger European basis for regulating the safety and efficacy of medicines.
Directives were introduced in 2001 to clarify and expand our mandate in the human and the veterinary medicines area, with new scientific evaluation committees established in critical areas of unmet health needs, such as orphan drugs. Then in 2004, we had the “big bang” — the entry into our network of 10 new EU member states, followed by two more in 2007. This brought significant challenges in coping with more players at the table while maintaining the commitment to efficient dossier management and timely appraisals.
We also saw the introduction of risk and surveillance management planning and the conditional approval track, where companies can gain expedited decisions on products for diseases that are severe and life-threatening and do not have substitutes on the market. Next, we had to respond to pressure to help speed the development of pediatric medicines, resulting in the creation of yet another scientific review committee. Because of the policy sensitivities and the complexity of the science, it was probably the most complicated set of rules anyone has ever had to introduce in Europe.
The Commission Regulation of 2004 also defined a role for the Agency in tracking the pace of scientific discovery to ensure our standards are relevant and supportive to what industry is seeking to deliver for patients. It resulted in legislation to create a Committee on Advanced Therapies to facilitate introduction of novel technologies, such as gene or cell therapies or tissue engineering. This is a real innovation for Europe, as no other national regulatory body has such a group dedicated to fostering timely introductions of the new medicines of the future. One of our key objectives at the Agency — in addition to certifying safety and efficacy — is to stimulate innovation and promote the availability of new medicines. Good regulation can facilitate that; the Advanced Therapy Committee is an example I am quite proud of.
Now that it’s largely complete, where would you say were the successes and the gaps of the first ‘road map’?
We achieved progress in three key areas, each of which was based on a close assessment of the environment for drug approval. One was the review of all our policies to benchmark whether they added to or detracted from the capacity of industry to conduct R&D, so that European patients would gain the clinical benefit from new therapies.
The second was to rigorously test our commitment to the highest level of safety, including ways to encourage the rational use of medicines to reduce the incidence of adverse events and to secure better rates of compliance.
Third, we re-examined the entire organization structure to see how to improve the flow of information, to communicate with external constituencies more effectively, and to make transparency the basis for everything we do. The one area where there is still a gap is transparency. Progress has been made but it is clearly a moving target. Compared to other agencies, we are ahead. But my sense is that here in Europe, our stakeholders are expecting more.
For example, a better definition is needed to classify what is commercially sensitive information. The European Ombudsman believes that the Agency should widen access to documents, and in the last few weeks we have moved further in that direction, making a pledge to allow disclosure of all documents — including adverse event reports — within 15 days of a request, subject to the conditions of data protection.
Another challenge is making sense of the enormous amount of data we generate on a daily basis. That data has to be transformed into useful information. It’s not easy; you cannot just go to the bottom of the pile and say, “This will be public and this will stay confidential.” Hence one of our objectives for the 2015 road map is to build the internal capabilities to leverage the volume of information productively.
What are the key priorities of the 2015 road map?
Final action on this awaits the decision of the Management Board, which meets this month and is slated to endorse both the road map and an accompanying “Vision to Reality” white paper. I would summarize the priorities to 2015 as follows:
1) maintain our core mission in approving new products through the European Regulatory Network;
2) fill gaps in the development of medicines for urgent health needs, such as antibiotics and the diseases of aging, and work with industry to address high attrition rates for many therapies;
3) adapt regulatory capacity to manage the growth of personalized medicine, through such means as setting standards for the qualification of biomarkers in cancer;
4) improve the scope of legislation covering veterinary medicines and finding better ways to create synergies with our work in the human field; and 5) create a stronger preparation/alert platform to manage public health crises as well as control the distribution of counterfeit drugs. There is a lot of continuation here, which is good, as we are building on success.
What do you think are the most important trends that will influence the actions of regulators, particularly in the relationship with the R&D industry?
Globalization represents a real game change for the regulator. The perception has been that there is a fixed geographic limit to our mandate. But over the last decade we have discovered that the products we regulate are researched in numerous sites, involving parties with different levels of skill or expertise; are subjected to clinical trials among increasingly diverse patient populations, in dozens of different countries; and are manufactured outside our territory, based on active ingredients formulated increasingly in China and India. The fundamental question is, can we trust that all this critical work done outside our “span of control” is safe, reliable, and in conformity to our rules?
Now that your tenure as Executive Director is ending, do you have any advice for the pharmaceutical industry going forward?
Drug companies need to do a better job at linking their prospects to the treatment and prevention of disease — not just today but especially for the future. Association with the development of advanced therapies like tissue replacement and modification of the immune system through vaccines is vital. Industry leaders also have to face the question of the limited resources available for health: Are we as a society spending these resources in the right way?
This in turn requires the possibility of acknowledging that pharmaceutical interventions are often overvalued. The best tool to solve a health challenge could be something other than a drug. Process innovation is not recognized by the industry as a source of growth. Horizontal prevention strategies, designing devices along with drugs to facilitate improved diagnoses and raise the patient response rate — these are ripe for new approaches. The current business model has to yield to something more holistic.
What advice might you have for your successor?
A firm commitment to transparency is critical to success in this position. Transparency is fundamental to trust. Trust is what fosters confidence in our networked authorization system and helps ensure that when there are problems, you have the political leverage to do what is right for public health. This is particularly important given EMA’s expanded remit in supervising the pharmacovigilance process.
The next Executive Director will also have to keep pace with progress in science and technology. New areas of regulation are opening up; more needs to be done to clarify standards, as we are doing now for biosimilar antibody drugs, where we are specifying approaches to postauthorization follow-up studies to better ensure patient safety.
The full version of this interview is available in December’s Pharm Exec.