Peter O’ Donnell

	The European Union's extensive transatlantic links have reached a further level of maturity with the completion at the end of 2014 of exchanges between the European Medicines Agency and Health Canada.

	An official from Health Canada has returned home after two years as a visiting national expert at EMA, where-among other things-he helped prepare the report to the European Commission on the agency’s implementation of pharmacovigilance tasks under the new EU legislation.

	At the same time, an EMA official has just completed a 14-month placement with Health Canada, where she contributed to a study on developing medicines for pediatric use, compiled by a 14-member panel of national and international experts with backgrounds in academia, the pharmaceutical industry, regulatory science, and clinical and medical fields. These exchanges come on top of existing regular sharing of information between the two agencies and interactions through topic-based expert ‘clusters’-notably, recently, on orphan drugs and labeling.

	The links with Canada complement the far broader and deeper relations that EMA enjoys with the US Food and Drug Administration. These are longstanding, but have recently benefited from new impetus. In this 

Applied Clinical Trials article, Peter O' Donnell explores this strengthening relationship

Articles

The European Union's extensive links with the US FDA and Health Canada have reached a further level of maturity, writes Peter O' Donnell.

EU Strengthens Transatlantic Links

	The entry into force of the new EU clinical trials regulation last June is really little more than a virtual event. The new rules will apply only once the EU Clinical Trials Portal and Database now under development are fully operational-and that isn't going to happen until 2016 at the earliest. In the meantime, there is a web of secondary legislation to be woven by the European Commission, which has to prepare and adopt a series of so-called delegated and implementing acts, as well as steer the process for the update of the related guidelines.

	The steps needed to drag the necessary platform into place include a delegated act on Good Manufacturing Practice which will detail arrangements for inspections of investigational medicinal products, and an implementing act on detailed arrangements for Good Clinical Practice inspections, including qualifications and training requirements for inspectors. The Commission currently intends to adopt both of them by mid-2016. The necessary updated guidelines will cover GMP and voluntary sharing of raw data. And the Commission is also empowered to adopt an implementing act on cooperation among national authorities in assessing safety reporting-although it is waiting to see what comes out of discussions within the clinical trials facilitation group that national agencies operate before deciding on whether that will be needed. That group cooperates with the Commission and EMA in a specially-created clinical trials regulation coordination group that has been established to permit effective exchanges among the different bodies with responsibilities for putting the new regulation into real effect.

	For the rest of this Applied Clinical Trials article, 

The entry into force of the new EU clinical trials regulation last June is really little more than a virtual event. The new rules will apply only once the EU Clinical Trials Portal and Database now under development are fully operational.

Clinical Trials in Europe: Dragging the New Rules into Operation

	So at last it’s happened. Adaptive licensing has leapt from the pages of learned journals into the real world of European regulation. Is this the beginning of the end of binary decision-making on the merits of a new medicine? Has a half-century of the “yes/no” authorization process peaked, to be replaced by staggered approval, or progressive licensing? After years of reflection on the theoretical merits of a rolling approach, the European Medicines Agency last week launched a pilot project to test how well the theory might work in practice, with real medicines in development.

	The agency is inviting companies to submit experimental medicines still in the early stage of clinical development as guinea pigs for this new approach-the latest attempt to strike the right balance between speeding up patient access to new medicines and ensuring patient safety. But to avoid giving the impression that caution is being thrown to the winds in the search for speed, the agency’s emphasis is on how the new approach is “prospectively planned.”

	Early authorization would be given for use of a medicine in only a restricted patient population, then a series of iterative phases of evidence-gathering would support subsequent adaptations of the marketing authorization, expanding access to the medicine to broader patient populations. But it goes further than the existing regulatory mechanisms of compassionate use or conditional authorization. Widening patient populations would have access to an innovative therapy in line with evolving information on the benefits and risks.

	Hans-Georg Eichler, the agency’s Senior Medical Officer, and one of the prominent advocates of adaptive licensing, says this could the way to “maximize the positive impact of new medicines on public health.” And the move has won immediate and explicit applause from some industry organizations. The decision “is to be welcomed,” said the UK’s Biotech Industry Association, which has campaigned for the introduction of adaptive licensing for years. “We will encourage our members to respond to the agency’s call for participation in the pilot project,” said its Executive Director, Steve Bates.

	Support from UK-based industry groupings is not surprising. Much of the pressure to move the adaptive licensing agenda forward has come from the UK, which has been mooting an early access scheme of its own for promising unlicensed medicines in areas of high unmet medical need. The UK regulatory authority has over recent months played a leading part in press for European-level action to make full use of all available legal flexibilities to get innovative products to patients.

	How fast the revolution will come is not so clear. In time-honored European fashion, everyone is to get a voice-regulators, industry, health technology assessment bodies, organizations that issue clinical treatment guidelines, patient organizations… “All discussions will take place in a ‘safe harbor’ environment,” insists the agency, which is aiming at “free exploration of the strengths and weaknesses of all options”-in development, assessment, licensing, reimbursement, monitoring, and pathways for use. And these options will be explored “in a confidential manner and without commitment from either side.” Not a recipe for rapid action.

	The evolution of the approach itself is going to be adaptive too. The pilot phase will cover “as many programs as necessary” to gather knowledge and experience, address technical and scientific questions, and refine the design of the adaptive pathway for different products and indications. And “as the project progresses, the European Commission will examine the legal and policy aspects related to adaptive licensing in collaboration with the EU member states and by consultation with relevant stakeholders, as necessary.”

	So if it is the beginning of the end of binary decisions, the end looks as if it is still a long, long way away.

So at last it’s happened. Adaptive licensing has leapt from the pages of learned journals into the real world of European regulation.

Adaptive Licensing: The Start of a Slow Revolution in Europe

	This week (February 28), Europe will celebrate Rare Disease Day. This is an interesting example – one might almost say a rare example – of a successful attempt by a European interest group to capture public attention. It is now an annual awareness-raising event co-ordinated by the European rare diseases lobby group, Eurodis.

	For this year’s celebration, on February 28, Eurordis has shown commendable imagination as well as energy in seeking to maximize the profile. It is, after all, a campaigning event by a campaigning organization. The main objective is to make sure that the general public and decision-makers take more notice of rare diseases and their impact on patients’ lives. So it targets not only the man or woman in the street, but also patients and patient representatives, politicians, public authorities, industry representatives, researchers, health professionals, and anyone who has a role in relation to rare diseases. For six months, Eurordis has been flagging up the event through media announcements, posters, social networks, mail shots, and even a video – and it has managed not only to make it look attractive, but to attract wide support. More than 70 countries across the world are taking part too, ranging – alphabetically and geographically – from Algeria and Argentina to Venezuela and Vietnam, and organizing everything from festivals and dinners to conferences and concerts.

	This year’s slogan, “Join Together for Better Care,” encourages the rare disease community to continue finding ways to work together to provide the different kinds of care that people living with a rare disease need. It explicitly aims to promote solidarity and to overcome the sense of isolation that many victims of rare diseases suffer. The success of this approach is neatly illustrated by a comment on the campaign’s Facebook page: “E’ sempre una grande emozione….l’attesa, la sorpresa, la gioia di condividerlo! Grazie Eurordis!” (It’s always a huge emotion… the expectation, the surprise, the joy of sharing it! Thank you Eurordis!)

	But the true success of the Rare Disease Day and all the associated campaigning will be judged against tougher criteria – in terms of how far it improves the current situation and future treatment of patients. Eurordis itself claims that “the political momentum resulting from the Day has also served for advocacy purposes. It has notably contributed to the advancement of national plans and policies for rare diseases in a number of countries.” What remains to be seen is how far this European organization can shape the political and regulatory environment governing rare disease research and treatment.

	Its Berlin conference in May, co-organized with the Drug Information Association, will represent a rather more hard-core confrontation with the decision-makers that influence the fate of rare disease sufferers. It will be examining opportunities in collaborative clinical research into rare diseases, the challenges of disease-specific registries, improvements to gene testing, and how to sustain investor interest in rare disease research.

	Another test is how Eurordis and its constituency will manage to benefit from the new expert group on rare diseases that the European Commission has created, and that held its first meeting in Luxembourg on 11-12 February. This replaces an earlier advisory forum, and one of the novelties is that EU officials have a much more prominent role in running the group. Above all, success for Eurordis and those it represents will depend crucially on the outcome over the next two years of the development and implementation of national plans for rare diseases. It will take more than a fancy website to make all that come right.

This week (February 28), Europe will celebrate Rare Disease Day. This is an interesting example – one might almost say a rare example – of a successful attempt by a European interest group to capture public attention.

Author | Peter O’ Donnell

Articles

EU Strengthens Transatlantic Links

Clinical Trials in Europe: Dragging the New Rules into Operation

Adaptive Licensing: The Start of a Slow Revolution in Europe

Europe: Expectations High for Rare Disease Day