Applied Clinical Trials
The tone of agency’s annual report contrasts its recent candid stance on regulatory vision for Europe
There is plenty to read in the European Medicines Agency's (EMA) just-published annual report for last year. But much of the attention of the clinical trials community will be directed to checking just how far this rather routine publication reflects a very new and very recent trend towards candor in the agency.
The sheer volume of the information in the annual report is, itself, remarkable, because the agency now has so many tasks reaching into so many corners of the world of pharmaceuticals. The report covers the core activity of recommending human-use medicines for European Union (EU) marketing authorization (82 in 2014)-and not all of these were routine, either. The year saw the first recommendation of a medicine for the treatment of Duchenne muscular dystrophy, the first treatment for erythropoietic protoporphyria, and the first therapy based on stem cells. Overall, 17 of the medicines that got the green light from the EMA were intended for the treatment of a rare disease-a new record.
It also covers the currently contentious subject of early EMA scientific support for companies developing medicines (health campaigners are claiming that it carries a risk of conflicts of interest), where the number of requests in 2014 set a new record, with three-quarters of applicants benefiting. The report notes the use of accelerated assessment procedures for medicines expected to be of major benefit for public health (seven positive opinions were granted through this route, including for four new-generation medicines for treating chronic hepatitis C virus (HCV) infection, led by Sovaldi). And it covers the equally contentious subject of transparency-with the EMA's adoption of its new policy on the publication of clinical data, the widening of the European database of suspected adverse reactions, its publication of agendas and minutes for the meetings of all its scientific committees.
New responsibilities are also reported on-with additional tasks imposed by the implementation of new EU legislation on pharmacovigilance (and, in 2014, new fees charged to industry for this increased monitoring)-falsified medicines (including producing new guidance for good manufacturing practice and good distribution practice inspections), and on clinical trials (creating the portal and database to be used for submitting applications for trial authorization).
Quality of work
So much for the routine. But of greater interest is the tone adopted for discussion of the quality of the agency's work.
"The European medicines regulatory network is the cornerstone of the work and success of the agency," it says, pointing to the "experts from national authorities carrying out the assessment of medicines on behalf of EMA." It goes on to comment that "to be able to carry out the work to a high level of quality, it is essential that more and more national authorities participate in the assessment of medicines."
The urgency in the expression of this ambition coincides with the message at the heart of a major strategy document that EMA published shortly before its annual report. "Regulatory capability varies across the network. Some national competent authorities have more expertise in certain areas than others," says "Network Strategy to 2020," a 25-page consultation document that clearly recognizes weak links among the member states. This document-which is open for comment until June 30, and describes itself as a "draft strategic vision"-insists: "The network must ensure that all national competent authorities that participate in a specific type of regulatory activity continue to have the capability to do so. A critical success factor for the network will be to have available and at its disposal sustainable high-quality scientific and regulatory expertise able to address progress in regulatory science."
In other words, right now, there isn't enough capacity, and what there is, is not always adequate to the task. The need exists, continues this consultation document, for "a clear identification of any gaps in scientific and regulatory expertise based on current and future needs, and a corresponding competence development program," as well as for "common standards of scientific quality across the EU regulatory network," and for strengthened output, "in particular the scientific quality of regulatory processes," to "mitigate discrepancies within the network."
The point was made very tersely by Professor Sir Alan Breckenridge, who told this columnist during the reception to celebrate the 20th birthday of the EMA: "The problem with the EMA is that there are 28 members but the contributors are about six. This is something that's got to be worked on, because there's huge variability in expertise across the whole of Europe. This is a real problem-because when it comes to a decision, all of the agencies have a vote, but about 20 of them don't have an idea of what they are voting on."
The problems-in many cases longstanding-have come to the surface because of the new challenges that drug regulators and drug innovators are facing. As EMA puts it, a new framework is needed to tackle new science and new economic constraints, and to find radical new responses to cater adequately for the health of Europe's citizens. New technologies, the changing nature of pharmaceutical innovation, new advanced therapies, new licensing pathways and product life-span approaches, greater use of real-world databases, the increasing globalization of the pharmaceutical industry, and new and emerging health threats-whether in the form of antimicrobial resistance or emerging epidemics, as demonstrated by the outbreak of Ebola, or through criminal activity such as falsification of medicines. It is important, EMA believes, that the network keeps abreast of these advances to ensure that novel products can be developed optimally for the benefit of the health of the citizens of Europe.
A more modest tone
The annual report takes a more modest approach to this challenge than does the EMA strategic vision-or Sir Alastair. It says there is "an important positive trend for the EU system," in that "efforts undertaken during the last few years are paying off." One positive factor is that more national authorities are becoming involved in EMA procedures as rapporteurs or co-rapporteurs (up from 16 in 2010 to 24 in 2014). But even the moderately-worded annual report does tacitly admit that more is necessary, and describes how the agency has tried during 2014 "to ensure its continuation," with the launch of initiatives that "aim to better support the assessment work of the many thousands of EU experts involved in the regulation of medicines."
One of these is the EU Network Training Centre, jointly operated by the EMA and the less formal group of heads of national medicines agencies in the EU. This is building "a training strategy for continuous professional development of staff from national competent authorities and EMA, in order to improve the quality, consistency, and efficiency of the work of the network and promote harmonized application of the regulatory framework and guidelines." Another is a new scheme in which the agency supports the creation of multinational co-rapporteur teams to assess initial marketing authorizations for medicines for human use, "to make use of the best expertise across the EU for the assessment of a marketing authorization application." It follows a successful pilot scheme.
The pilot involved Denmark, Estonia, Finland, Latvia, Lithuania, Poland, and Sweden, as well as Iceland and Norway (which are closely associated with EMA, even if they are not EU member states). EMA has found it so useful, it is now exploring how the scheme can be extended.
So two tones are evident as the 20-year-old EMA experiences its epiphany. One is candid to the point of being undiplomatic. The other is more measured. But it is striking that the moderate tone in the annual report belongs to things of the past. The more assertive tone, as in the "draft strategic vision," is very much geared to the future.
Peter O'Donnell is a freelance journalist who specializes in European health affairs and is based in Brussels, Belgium.