The spring in Europe has been marked by some unusual — even unprecedented — alliances in the world of pharmaceuticals. The most conspicuous example is a strategic coalition formed among some of the most unlikely bedfellows ever to snuggle down together under a common blanket: manufacturers, wholesalers, pharmacists and — yes, believe it or not, it’s true! — parallel importers.
This is the plan for a self-styled “joint stakeholder-run verification system of pharmaceutical products in Europe,” which is currently being signed up to by a clutch of key industry associations and their members.
To see the European Federation of Pharmaceutical Industries and Associations (EFPIA) —representing the brand-name research-based companies in Europe — sitting amicably at the same table as the European Association of Euro-Pharmaceutical Companies —representing Europe’s flourishing parallel importers — is a bizarre spectacle to anyone who has seen these two outfits squaring up to one another for decades, and slugging it out relentlessly in the European Court of Justice over the most fundamental values of safety, intellectual property rights and money.
There is not a politician, official, diplomat or journalist in Brussels who has not, over the years, been deluged with rival arguments from these two lobbies, with parallel traders invoking the sacred EU principles of free circulation and extolling the merits of cheaper drug supply, and manufacturers warning that parasitical middlemen threatened a meltdown in the research cycle. But now they two sides are, on paper at least, the best of friends. Mirroring the life now bursting vigorously from the winter-blackened twigs and frost-hardened soils of Europe, these organisations are “committed,” according to a memorandum of understanding they are formally endorsing, “to working together to establish an efficient, viable and effective system to protect patients.”
What is the threat that has triggered this unexpected concord? On the face of it, it is counterfeiting. The coalition represents a common effort in pursuit of the commendable objective of preventing bogus drugs reaching the public. At a more pragmatic level, the motivation is money.
The EU’s new legislation aimed at combating falsified medicines will require the introduction of harmonised pan-European safety features in the form of tamper evident packaging, along with a unique pack identifier, linked to data repositories to allow verification that a pack is genuine. The details are not laid down in the primary legislation, but will be specified over the coming years by secondary legislation. But whatever the system consists of, it is going to be expensive. The law stipulates that the costs of repository systems will be borne by the holders of marketing authorisations. And wholesalers and pharmacists also face costs in adapting their own systems to fit.
This is what is behind the memorandum of understanding, which also embraces GIRP, the European association of pharmaceutical full-line wholesalers, and PGEU, the community pharmacists’ organisation in Europe. Since big costs are going to be incurred, these organisations have come together early to design the most appropriate response to these obligations, so that the money they are all going to have to spend is at least spent on something that will work for them. Or, as they put more politely in their memorandum, they are collaborating “with a view to jointly promoting the development of a cost effective and scalable product verification system.”
Health Technology Assessment
It isn’t just within the industry that new forms of cooperation are flourishing. The common funding problems faced by healthcare agencies are driving them to new forms of working together — giving rise to, among other manifestations, the boom in health technology assessment (HTA). For the European Union, “HTA is an important part of evidence-based health decision-making,” and “to enhance cooperation between countries,” the EU is preparing to set up “a permanent, voluntary HTA network in Europe, “to facilitate efficient use of HTA resources, to create a sustainable system of knowledge-sharing, and to promote good practice in methods and processes.” It has new legal backing to do this, through the coming into force of the 2011 legislation on patient rights in cross-border healthcare, and it is determined to exploit this to the full.
Already the EU is supporting joint action in this field through the European network for health technology assessment (EUnetHTA), which now involves 24 of the EU’s 27 member states, plus Norway and Switzerland. This network of national agencies is not merely developing academic collaboration at EU level on sharing and reuse of HTA information. It is also getting into the business of defining relative safety and efficacy, and developing models of governance. And it is producing joint scientific assessments on pharmaceuticals.
Unsurprisingly, the pharma industry wants to know where all this is going, since it concerns matters so central to its continued success. So it too has decided to get in on the act, rather than just carping from the auditorium. At the last ceremonial high mass of EUnetHTA, in Gdansk at the end of last year, an industry delegation was accepted into the troupe of healthcare agencies — and even allowed to perform.
A senior Glaxo executive, Andrea Rappagliosi, representing half-a-dozen industry associations — including devices and diagnostics, delivered a “healthcare industry view” of HTA, “now and in the future.” And his message, although hedged cautiously, was that industry is ready to come aboard, in the interests of healthcare as well as in the interests of its own self-preservation. It is willing to engage in dialogue on governance issues, in a bid to have a say at the right stage in creating assessment methodologies, identifying relevant assessment criteria, and setting up pilot programmes. The lamb and the lion will, even if slightly nervously, be sitting together as HTA evolves in Europe.
But perhaps the most seismic shift underway in the world of pharmaceuticals — in Europe and beyond — is the growing challenge of getting new medicines (and particularly more targeted medicines) to the patient early, safely, and profitably. Strategists puzzling over this conundrum, among industry and regulators, are increasingly speculating that the classic approach to drug registration is reaching its own sell-by date.
One of the most incisive contributions to this debate has come from a team led by Hans-Georg Eichler, which has examined how far adaptive licensing might offer a solution. The basis thesis is that traditional drug licensing approaches are no longer entirely appropriate, since they are based on binary decisions - in other words, a sudden-death yes-or-no once-for-all decision about the adequacy of a proposed medicine. A ‘yes’ decision under this approach implies that, at the moment of licensing, an experimental therapy becomes a fully vetted, safe, efficacious therapy - clearly at odds with the reality.
By contrast, argue Eichler and his team, adaptive licensing approaches authorisation with the assumption that learning about a drug’s merits is stepwise, under conditions of acknowledged uncertainty, with successive phases of data gathering and regulatory evaluation. Because this corresponds more closely to the reality of drug development and use, it holds out the prospect of a better fit - to patient needs, to medical science, and even to the interests of research-based companies. It could break the vicious circle of agencies requiring ever more data before authorisation, in turn imposing higher costs and greater delays on developers, and potentially discouraging innovation.
At the heart of the many variants on adaptive licensing is a readiness by drug companies and regulatory agencies to collaborate more closely and at an earlier stage in planning the development of a product and in agreeing evidence gathering methods that will allow incremental certainty over the product’s characteristics and corresponding modifications to the product licence. As the Eichler paper concludes: “an adaptive route to market that comprises successive licensing steps, more forthright communication about unavoidable uncertainty and knowledge gaps, progressive reduction of uncertainty, and alignment of drug utilization with current knowledge will mitigate some of the current disconnects between industry, regulators, and their different stakeholders and engender public and political trust in the regulatory system.”
Peace may not yet have been declared across the healthcare sector, but among the blossoms of the spring it is possible to perceive a number of intriguing olive branches.
 Clinical Pharmacology & Therapeutics | VOLUME 91 NUMBER 3 | March 2012