Brexit will Hollow Out Europe's Drug Development Framework

The shocking result of the UK's referendum on EU membership will have a severe impact on the way that medicines are developed in Europe-in addition to the reverberations now shaking the world's economic, financial and geopolitical context.  

In its broadest terms, UK withdrawal from the EU will interrupt, invert and subvert the process of integration that has shaped health and pharmaceutical policy for more than half a century. And in more concrete form, it will seriously damage many of the carefully-constructed frameworks that have been put in place to improve the safety of medicines and to promote innovation and efficient deployment of healthcare resources.

Collaboration, networking, cooperation have been the consistent mantras of pharmaceutical policy in the EU. Only this month, when EU Commissioner Vytenis Andriukaitis addressed a European drug industry meeting in The Netherlands, he concluded by "stressing my firm belief in the added value of working together in partnership and in full transparency across the European Union to the benefit of EU citizens, creating trust of citizens, and increasing the efficiency of our healthcare systems."

Neither he nor anyone else in the European healthcare world took seriously the threat of a "Leave" vote in the UK on Thursday. Now he, and everyone else in Europe or beyond who has an interest in health policy, is standing in amazement and disbelief amid the wreckage of decades of painstaking construction of better systems for controlling and delivering medicines, contemplating a bleak and diminished future.

All of a sudden, all those noble aspirations and comfortable assumptions have been revealed as hollow. "The Commission is working with experts from the member states and the European Medicines Agency (EMA) on optimizing the current marketing authorization systems," said Andriukaitis. "We want to see better use of existing regulatory tools that facilitate the development and timely assessment and authorization of such medicines. This is hopefully the vision for the future."

Less hope now!

The same consternation is evident in the EMA, the engine-room of much of Europe's pharmaceutical policy-making, resplendent in its brand-new London headquarters-which it will now have to abandon for a new location in another member state. By a cruel irony, EMA celebrated its 20th anniversary just over a year ago, and has recently agreed on a new five-year strategy which was, for the first time, in a bold new phase of cooperation, developed jointly with the heads of medicines agencies in the member states.

There is now a hollow ring to the words that Kent Woods, outgoing chair of the EMA Management Board, wrote in the agency's just-published annual report. "Over the past 12 years, I have seen a steady strengthening of the EU network comprising EMA, the national regulatory authorities and the Commission. This is a unique structure, bound together by a shared commitment to the application of best science for the benefit of public and animal health." That commitment is not anymore shared, as a result of the views of 17 million British voters.

Similarly, Guido Rasi, freshly reappointed, to universal acclaim, as executive director of EMA, wrote in his introduction to the annual report of his ambition "to reflect and discuss with our EU partners how we can support and shape the transformation the medicine development and authorization system is currently undergoing in order to improve the health of EU citizens." Little did he imagine when he wrote those words that the transformation would be quite so drastic and brutal as the UK referendum will now make it.

What will now happen to the EU's Clinical Trials Regulation agreed only last year-and due for implementation as from now. EMA has been creating the clinical trial portal and database for what EMA calls "this ambitious new piece of legislation, which is leading to the most significant overhaul of the processes for authorization and oversight of clinical trials in the last two decades." Designed to provide seamless links to all trials in the EU, suddenly it is going to be linking to trials conducted only in some of the countries of Europe-and one of the principal countries for conducting trials is not going to be included.

What are the prospects now for the coordinated approach that is recognized as essential in combating antimicrobial resistance (AMR)? In January, EMA produced a joint analysis-together with the European Center for Disease Prevention and Control and the European Food Safety Authority-of the consumption of antimicrobial agents and the occurrence of AMR in bacteria in humans and food-producing animals. This was the first time that data from humans, animals and food in Europe were analyzed together. As EMA says, public health challenges do not stop at borders, and this study was one step in "providing valuable insights for policy-makers across the EU."

The outbreak of the Ebola virus "reinforced the agency’s commitment toward ever-closer cooperation between regulatory authorities worldwide in order to promote and protect public health around the globe," it goes on. Difficult to see just how closely UK regulatory authorities will be cooperating when they have been dragged by their electorate out of the club.

So many other joint activities are now under an existential threat because of Brexit: finalization of the new EU rules on pharmacovigilance, faster market access programs such as PRIME, the adaptive pathways pilot project, the next phase of Europe's health technology assessment coordination, refinement of the strategy on pediatric medicines development, preventing and managing drug shortages, scientific advice for post-authorization safety studies, implementation of the Falsified Medicines Directive, the new electronic repository for periodic safety update reports that "ensures that all people involved in benefit-risk assessments of medicines have timely access to all relevant documents in one location"… the list goes on and on.

"These challenges require a holistic and global approach," says EMA. It adds that "None of the successes achieved in 2015 would have been possible without the network of European medicines regulatory agencies. This network gives EMA access to a pool of excellent scientists from across Europe, allowing the agency to source the best-available experts for the regulation of medicines in the EU."

And why should the departure of just one member state have such dramatic consequences? Not because it is the host to EMA, but because it is one of the biggest member states, an acknowledged leader in the life sciences, and a highly-respected contributor to EU discussions on medicines development, regulation and use.

It is also the biggest contributor to the EU's expertise in medicines. As EMA says, "the EU member states make available around 4,500 experts who carry out the evaluation of medicines on behalf of EMA and are members of the agency’s scientific committees, working parties and scientific advisory groups. This pool of experts allows EMA to source the best-available scientific expertise for the regulation of medicines, and ensures that the assessment activities as well as the scientific guidance produced by EMA are of high quality."

And by way of simple numerical example of the gaps that will open up, in 2015, the UK provided 39 senior advisers (rapporteurs and co-rapporteurs), compared to Germany's 25, Austria's 14 and Italy's 11. That is some gap to fill.